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WO2018153546A1 - Tetrahydropyran and tetrahydrothiopyran methanone derivatives having multimodal activity against pain - Google Patents

Tetrahydropyran and tetrahydrothiopyran methanone derivatives having multimodal activity against pain Download PDF

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Publication number
WO2018153546A1
WO2018153546A1 PCT/EP2018/000079 EP2018000079W WO2018153546A1 WO 2018153546 A1 WO2018153546 A1 WO 2018153546A1 EP 2018000079 W EP2018000079 W EP 2018000079W WO 2018153546 A1 WO2018153546 A1 WO 2018153546A1
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unsubstituted
substituted
alkyl
compound
alkenyl
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Carmen ALMANSA-ROSALES
Monica Garcia-Lopez
Sergio Rodriguez Escrich
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Laboratorios Del Dr. Esteve, S.A.
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Publication of WO2018153546A1 publication Critical patent/WO2018153546A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • X is a bond or -0-
  • the compound according to the invention of general Formula (I) is a compound of general Formula (I 5 ')
  • diastereomers a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • Rs and R5' are independently selected from halogen, -Rn, -ORn, -NO2, - NRnR ', -NRnC(0)Rir, -NRnS(0) 2 Rir, -S(0) 2 NRnRir, -NRnC(0)NRirR i , -SR11 , -S(0)Rii, -S(0) 2 Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, - C(0)NRiiRir, -OCH 2 CH 2 ORn, -NRnS(0) 2 NRn R i r and -C(CH 3 ) 2 ORn; and R 1 1 , Ru and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C 2 -6 alkenyl and unsubstituted C 2 -e alkynyl. optionally in form of one of the stereoisomers, preferably
  • diastereomers a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • cycloalkyi is understood as meaning saturated and unsaturated (but not aromatic) cyclic hydrocarbons (without a heteroatom in the ring), which can be unsubstituted or once or several times substituted.
  • C3-4- cycloalkyl represents C3- or C4-cycloalkyl
  • C3-5-cycloalkyl represents C3-, C4- or C5- cycloalkyl
  • C 3 - 6 -cycloalkyl represents C3-, C4-, C5- or C6-cycloalkyl
  • C 3 -7-cycloalkyl represents C3-, C4-, C5-, C6- or C7-cycloalkyl
  • C 3 -8-cycloalkyl represents C3-, C4-, C5- , C6-, C7- or C8-cycloalkyl
  • C 4 -5-cycloalkyl represents C4- or C5-cycloalkyl
  • physiologically acceptable salt means in the context of this invention any salt that is physiologically tolerated (most of the time meaning not being toxic- especially not caused by the counter-ion) if used appropriately for a treatment especially if used on or applied to humans and/or mammals.
  • physiologically acceptable salts can be formed with cations or bases and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention - usually a (deprotonated) acid - as an anion with at least one, preferably inorganic, cation which is physiologically tolerated - especially if used on humans and/or mammals.
  • W is -C(RwRw)- or -N(R W )-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein
  • Rw is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • Ri 3 and R13' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C 2 -& alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • Ri4, Ri 4 ' and Ri 4 - are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • m is 0, 1 or 2; and/or
  • q is 1 , 2 or 3;
  • R5 and R5' are independently selected from halogen, -Rn, -ORn, -NO2, -NRnRir, - NRiiC(0)Rir, -NRnS(0) 2 ir, -S(0) 2 NRnRir, -NRnC(0)NRirRir, -SRn , -S(0)Rn, - S(0) 2 Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnRir, -OCH 2 CH 2 ORn, - NRnS(0) 2 NRii Rir and -C(CH 3 ) 2 ORn; wherein the alkyl is Ci-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the alkyl is methyl; and/or Ri i , Ri i and
  • Ri 4 , Ri 4 ' and Ri 4 - are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; wherein the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyn
  • the compound is a compound, wherein p is 1 , 2 or 3; preferably p is 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R2 is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2 . 6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
  • R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C 2 . 6 alkenyl, substituted or unsubstituted C 2 . 6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
  • Ri 2 , Ri 2 and Ri 2 - are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C 2 -6 alkenyl and unsubstituted C 2 -e alkynyl ;
  • R 1 2, Rib and Ri 2 are independently selected from hydrogen, unsubstituted C 1 -6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C 2 -e alkynyl ;
  • R 4 " and R 4 - are both hydrogen, while R 4 and R 4 are both substituted or unsubstituted methyl; more preferably while R 4 and R 4 ' are both unsubstituted methyl.

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Abstract

The present invention relates to tetrahydropyran and tetrahydrothiopyran methanone derivatives having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

Description

TETRAHYDROPYRAN AND TETRAHYDROTHIOPYRAN METHANONE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN.
FIELD OF THE INVENTION
The present invention relates to compounds having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opioid receptor (MOR or mu-opioid receptor) and more particularly to tetrahydropyran and tetrahydrothiopyran methanone derivatives having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain. BACKGROUND OF THE INVENTION
The adequate management of pain constitutes an important challenge, since currently available treatments provide in many cases only modest improvements, leaving many patients unrelieved [Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet 377, 2226-2235 (201 1 )]. Pain affects a big portion of the population with an estimated prevalence of around 20% and its incidence, particularly in the case of chronic pain, is increasing due to the population ageing. Additionally, pain is clearly related to comorbidities, such as depression, anxiety and insomnia, which lead to important productivity losses and socio-economic burden [Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health. 1 1 , 770 (201 1 )]. Existing pain therapies include non-steroidal anti-inflammatory drugs (NSAIDs), opioid agonists, calcium channel blockers and antidepressants, but they are much less than optimal regarding their safety ratio. All of them show limited efficacy and a range of secondary effects that preclude their use, especially in chronic settings.
As mentioned before, there are few available therapeutic classes for the treatment of pain, and opioids are among the most effective, especially when addressing severe pain states. They act through three different types of opioid receptors (mu, kappa and gamma) which are transmembrane G-protein coupled receptors (GPCRs). Still, the main analgesic action is attributed to the activation of the μ-opioid receptor (MOR). However, the general administration of MOR agonists is limited due to their important side effects, such as constipation, respiratory depression, tolerance, emesis and physical dependence [Meldrum, M.L. (Ed.). Opioids and Pain Relief: A Historical Perspective. Progress in Pain Research and Management, Vol 25. IASP Press, Seattle, 2003]. Additionally, MOR agonists are not optimal for the treatment of chronic pain as indicated by the diminished effectiveness of morphine against chronic pain conditions. This is especially proven for the chronic pain conditions of neuropathic or inflammatory origin, in comparison to its high potency against acute pain. The finding that chronic pain can lead to MOR down-regulation may offer a molecular basis for the relative lack of efficacy of morphine in long-term treatment settings [Dickenson, A.H., Suzuki, R. Opioids in neuropathic pain: Clues from animal studies. Eur J Pain 9, 1 13-6 (2005)]. Moreover, prolonged treatment with morphine may result in tolerance to its analgesic effects, most likely due to treatment-induced MOR down-regulation, internalization and other regulatory mechanisms. As a consequence, long-term treatment can result in substantial increases in dosing in order to maintain a clinically satisfactory pain relief, but the narrow therapeutic window of MOR agonists finally results in unacceptable side effects and poor patient compliance.
The sigma-1 (σι) receptor was discovered 35 years ago and initially assigned to a new subtype of the opioid family, but later on and based on the studies of the enantiomers of SKF-10,047, its independent nature was established. The first link of the σι receptor to analgesia was established by Chien and Pasternak [Chien CC, Pasternak GW. Sigma antagonists potentiate opioid analgesia in rats. Neurosci. Lett. 190, 137-9 (1995)], who described it as an endogenous anti-opioid system, based on the finding that σι receptor agonists counteracted opioid receptor mediated analgesia, while σι receptor antagonists, such as haloperidol, potentiated it.
Many additional preclinical evidences have indicated a clear role of the σι receptor in the treatment of pain [Zamanillo D, Romero L, Merlos M, Vela JM. Sigma 1 receptor: A new therapeutic target for pain. Eur. J. Pharmacol, 716, 78-93 (2013)]. The development of the σι receptor knockout mice, which show no obvious phenotype and perceive normally sensory stimuli, was a key milestone in this endeavour. In physiological conditions the responses of the σι receptor knockout mice to mechanical and thermal stimuli were found to be undistinguishable from WT ones but they were shown to possess a much higher resistance to develop pain behaviours than WT mice when hypersensitivity entered into play. Hence, in the σι receptor knockout mice capsaicin did not induce mechanical hypersensitivity, both phases of formalin-induced pain were reduced, and cold and mechanical hypersensitivity were strongly attenuated after partial sciatic nerve ligation or after treatment with paclitaxel, which are models of neuropathic pain. Many of these actions were confirmed by the use of σι receptor antagonists and led to the advancement of one compound, S1 RA, into clinical trials for the treatment of different pain states. Compound S1 RA exerted a substantial reduction of neuropathic pain and anhedonic state following nerve injury (i.e., neuropathic pain conditions) and, as demonstrated in an operant self-administration model, the nerve- injured mice, but not sham-operated mice, acquired the operant responding to obtain it (presumably to get pain relief), indicating that σι receptor antagonism relieves neuropathic pain and also address some of the comorbidities (i.e., anhedonia, a core symptom in depression) related to pain states.
Pain is multimodal in nature, since in nearly all pain states several mediators, signalling pathways and molecular mechanisms are implicated. Consequently, monomodal therapies fail to provide complete pain relief. Currently, combining existing therapies is a common clinical practice and many efforts are directed to assess the best combination of available drugs in clinical studies [Mao J, Gold MS, Backonja M. Combination drug therapy for chronic pain: a call for more clinical studies. J. Pain 12, 157-166 (2011)]. Hence, there is an urgent need for innovative therapeutics to address this unmet medical need.
As mentioned previously, opioids are among the most potent analgesics but they are also responsible for various adverse effects which seriously limit their use.
Accordingly, there is still a need to find compounds that have an alternative or improved pharmacological activity in the treatment of pain, being both effective and showing the desired selectivity, and having good "drugability" properties, i.e. good pharmaceutical properties related to administration, distribution, metabolism and excretion.
Thus, the technical problem can therefore be formulated as finding compounds that have an alternative or improved pharmacological activity in the treatment of pain.
In view of the existing results of the currently available therapies and clinical practices, the present invention offers a solution by combining in a single compound binding to two different receptors relevant for the treatment of pain. This was mainly achieved by providing the compounds according to the invention that bind both to the μ-opioid receptor and to the σι receptor.
SUMMARY OF THE INVENTION
The main object of the invention is in one aspect directed to tetrahydropyran and tetrahydrothiopyran methanone derivatives having a dual activity binding to the σι receptor and the μ-opioid receptor for use in the treatment of pain.
As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the σι receptor and the μ-opioid receptor it is a very preferred embodiment if the compound has a binding expressed as K, which is preferably < 1000 nM for both receptors, more preferably < 500 nM, even more preferably < 100 nM.
More particularly the main aspect of the invention refers to a compound of general Formula (I),
Figure imgf000005_0001
(I) wherein Ri, R2, R3, 4, R4 , R4 , R4", Y, W, m, n, p, q and r are as defined below in the detailed description.
A further object of the invention refers to the processes for preparation of compounds of general formula (I).
A still further object of the invention refers to the use of some intermediate compounds for the preparation of a compound of general formula (I). It is also an object of the invention a pharmaceutical composition comprising a compound of formula (I).
Finally, it is an object of the invention the use of compound as a medicament and more particularly for the treatment of pain and pain related conditions.
DETAILED DESCRIPTION OF THE INVENTION
The invention is directed to a family of structurally distinct to tetrahydropyran and tetrahydrothiopyran methanone derivatives which have a dual pharmacological activity towards both the sigma (σ) receptor and the μ-opioid receptor, thus solving the above problem of identifying alternative or improved pain treatments by offering such dual compounds.
The invention is directed to compounds having a dual activity binding to the σι receptor and the μ-opioid receptor for use in the treatment of pain.
As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the σι receptor and the μ-opioid receptor it is a preferred embodiment if the compound has a binding expressed as K, which is preferably < 1000 nM for both receptors, more preferably < 500 nM, even more preferably < 100 nM.
The applicant has surprisingly found that the problem of providing a new effective and alternative for treating pain and pain related disorders can be solved by using a multimodal balanced analgesic approach combining two different synergistic activities in a single drug (i.e., dual ligands which are bifunctional and bind to μ-opioid receptor and to σι receptor), thereby enhancing the opioid analgesia through the σι activation without increasing the undesirable side effects. This supports the therapeutic value of a dual MOR/ σι receptor compound whereby the σι receptor binding component acts as an intrinsic adjuvant of the MOR binding component.
This solution offered the advantage that the two mechanisms complement each other in order to treat pain and chronic pain using lower and better tolerated doses needed based on the potentiation of analgesia but avoiding the adverse events of μ-opioid receptor agonists.
A dual compound that possess binding to both the μ-opioid receptor and to the σι receptor shows a highly valuable therapeutic potential by achieving an outstanding analgesia (enhanced in respect to the potency of the opioid component alone) with a reduced side-effect profile (safety margin increased compared to that of the opioid component alone) versus existing opioid therapies.
Advantageously, the dual compounds according to the present invention would show one or more the following functionalities: σι receptor antagonism and μ-opioid receptor agonism. It has to be noted, though, that both functionalities "antagonism" and "agonism" are also sub-divided in their effect into subfunctionalities like partial agonism or inverse agonism. Accordingly, the functionalities of the dual compound should be considered within a relatively broad bandwidth.
An antagonist on one of the named receptors blocks or dampens agonist-mediated responses. Known subfunctionalities are neutral antagonists or inverse agonists.
An agonist on one of the named receptors increases the activity of the receptor above its basal level. Known subfunctionalities are full agonists, or partial agonists.
In addition, the two mechanisms complement each other since MO agonists are only marginally effective in the treatment of neuropathic pain, while σι receptor antagonists show outstanding effects in preclinical neuropathic pain models. Thus, the σι receptor component adds unique analgesic actions in opioid-resistant pain. Finally, the dual approach has clear advantages over MOR agonists in the treatment of chronic pain as lower and better tolerated doses would be needed based on the potentiation of analgesia but not of the adverse events of MOR agonists. A further advantage of using designed multiple ligands is a lower risk of drug-drug interactions compared to cocktails or multi-component drugs, thus involving simpler pharmacokinetics and less variability among patients. Additionally, this approach may improve patient compliance and broaden the therapeutic application in relation to monomechanistic drugs, by addressing more complex aetiologies. It is also seen as a way of improving the R&D output obtained using the "one drug-one target" approach, which has been questioned over the last years [Bornot A, Bauer U, Brown A, Firth M, Hellawell C, Engkvist O. Systematic Exploration of Dual-Acting Modulators from a Combined Medicinal Chemistry and Biology Perspective. J. Med. Chem, 56, 1 197-1210 (2013)].
In its broader aspect, the present invention is directed to compounds of general Formula (I):
Figure imgf000008_0001
wherein m is 0, 1 or 2; r is 0, 1 or 2; n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3;
X is a bond or -0-;
Y is selected from -O- and
W is-C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
Ri is selected from substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R4 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R4 and R \ may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyi; R4 and R4 are independently selected from hydrogen, substituted or unsubstituted Ci- 6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R4- and R4", may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
These compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another embodiment, these compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (Γ)
Figure imgf000010_0001
(Γ) wherein Ri , R2, R3, R4, R4 , R4 , R4' , X, W, m, n, p, q and r are as defined below in the detailed description; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (la)
Figure imgf000011_0001
(la) wherein Ri , R2, R3, R ", R4-, X, W, p, and q are as defined below in the detailed description; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I2')
Figure imgf000012_0001
(I2) wherein R2, R3, R4, R4 , R4-, R4-, X, W, m, n, p, q and r are as defined below in the detailed description, and wherein
R5 and R5' are independently selected from halogen, -Rn, -ORn, -NO2, - NRiiRir, -NRnC(0)Rir, -NRiiS(0)2Rir, -S(0)2NRnRir, -NRnC(0)NRirRir, - SR11 , -S(0)Rii, -S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, - C(0)NRnRii , -OCH2CH2OR11, -NRiiS(0)2NRirRii» and -C(CH3)2ORn; and R11, Ru and Rn-are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or
diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I3')
Figure imgf000013_0001
(I3) wherein R2, R3, X, W, m, n, p, q and r are as defined below in the detailed description, and wherein R5 and R5' are independently selected from halogen, - Rii, -ORii, -NO2, -NR11R11., -NR,iC(0)Rii-, -NRnS(0)2Riv, -S(0)2NRiiRii-, -
NRnC(0)NRirRii", -SRn , -S(0)Rn, -S(0)2Rn, -CN, haloalkyl, haloalkoxy, - C(0)ORii, -C(0)NRnRir, -OCH2CH2ORn, -NRnS(0)2NRivRn» and -
Figure imgf000013_0002
and R11, Rir and Rn-are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2.e alkenyl and unsubstituted C2-6 alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I4')
Figure imgf000014_0001
(H.
wherein R2, R3, X, W, n, p and q are as defined below in the detailed description, and wherein R5 and R5 are independently selected from halogen, -Rn, -ORn, - N02, -NRnRir, -NR C(0)Rn , -NR S(0)2Rir, -S(0)2NRnRir, - NRiiC(0)NRivRir, -SRn , -S(0)Rn, -S(0)2Rn, -CN, haloalkyl, haloalkoxy, - C(0)ORii, -C(0)NRnRn , -OCH2CH2ORn, -NRnS(0)2NRirRir and - C(CH3)2ORn; and R11, Rir and Rn-are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-e alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I5')
Figure imgf000015_0001
(Ι5'),
wherein R2, R3, X, W and q are as defined below in the detailed description, and wherein R5 and R5' are independently selected from halogen, -Rn, -ORn, -NO2, -NR11 R11', -NR C(0)Rir, -NRnS(0)2Rir, -S(0)2NRiiRir, -NRnC(0)NRii-Rii», -SR11 , -S(0)Rii, -S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, - C(0)NRiiRir, -OCH2CH2ORn, -NRnS(0)2NRn Ri and -C(CH3)2ORn; and R11 , Rn- and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-e alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or
diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l5a')
Figure imgf000016_0001
o
wherein R2, R3, Rw, X and q are as defined below in the detailed description, and wherein
Rs and R5' are independently selected from halogen, -Rn, -ORn, -NO2, - NRnR ', -NRnC(0)Rir, -NRnS(0)2Rir, -S(0)2NRnRir, -NRnC(0)NRirRi , - SR11 , -S(0)Rii, -S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, - C(0)NRiiRir, -OCH2CH2ORn, -NRnS(0)2NRn Ri r and -C(CH3)2ORn; and R11 , Ru and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-e alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or
diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l5b')
Figure imgf000017_0001
o
wherein R2, R3, Rw, Rw', X and q are as defined below in the detailed description, and wherein
R5 and R5' are independently selected from halogen, -Rn, -ORn, -NO2, - NR11 R11', -NRnC(0)Rir, -NRnS(0)2Rir, -S(0)2NRnRir, -NRnC(0)NRi rRir, - SR11 , -S(0)Rii, -S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, - C(0)NRnRir, -OCH2CH2OR11, -NR11S(0)2NRi R1i and -C(CH3)2ORn; and R11 , R1 1 and Rn are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2.6 alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or
diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
For clarity purposes, all groups and definitions described in the description and referring to compounds of general Formula (I), also apply to compounds of general Formula (Γ), (la), (I2'), (I3'), (I4'), (I5'), (l5a') and (l5 '), as well as to all the intermediates of synthesis, when those groups are present in the mentioned general Markush formulae, since compounds of general Formula (Γ), (la), (I2'), (I3'), (I4'), (I5'), (l5a') and (l5b')> are included within the scope of the larger definition of general Formula (I). For clarity purposes, the general Markush Formula (I)
Figure imgf000018_0001
(I) is equivalent to
Figure imgf000018_0002
(IZ) wherein only the -CH2- groups are included into the brackets and m, n, p, q or r mean the number of times that said -CH2- groups are repeated. The same would apply, when applicable, mutatis mutandis to general Markush Formulae (I), (Γ), (la), (I2'), (I3'), (I4'), (I5'), (l5a') and (l5b'), and to all intermediates of synthesis.
In addition, and for clarity purposes, it should further be understood that naturally if m is 0, -C(R4R4 )- is still present, when applicable, in general Markush Formulae (I), (Γ) or (I2'), or if r is 0, -C(R4 R )- is still present, when applicable, in general Markush Formulae (I), ( ) or (I2'). This applies also in the particular case when R4 and R4 > are hydrogen or methyl, and/or when R4 and R4 are hydrogen or methyl, like in Markush Formula (I3').
It should also be understood that naturally if n is 0, then W is still present in general Markush Formulae (I), (Γ), (I2'), (I3') and (I4') or if q is 0, then X-R2 is still present in general Markush Formulae (I), (la), (Γ), (I2'), (I3'), (I4'), (I5'), (l5a') and (l5b').
In the context of this invention, alkyl is understood as meaning saturated, linear or branched hydrocarbons, which may be unsubstituted or substituted once or several times. It encompasses e.g. -CH3 and -CH2-CH3. In these radicals, Ci-2-alkyl represents C1- or C2-alkyl, Ci-3-alkyl represents C1-, C2- or C3-alkyl, Ci-4-alkyl represents C1-, C2-, C3- or C4-alkyl, Ci-s-alkyl represents C1-, C2-, C3-, C4-, or C5-alkyl, Ci-6-alkyl represents C1-, C2-, C3-, C4-, C5- or C6-alkyl, Ci-7-alkyl represents C1-, C2-, C3-, C4- , C5-, C6- or C7-alkyl, Ci-8-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7- or C8- alkyl, Ci-10-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9- or C10-alkyl and Ci-18-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9-, C10-, C11-, C12-, C13-, C14-, C15-, C16-, C17- or C18-alkyl. The alkyl radicals are preferably methyl, ethyl, propyl, methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1 ,1-dimethylethyl, pentyl, 1 ,1-dimethylpropyl, 1 ,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1- methylpentyl, if substituted also CHF2, CF3 or CH2OH etc. Preferably alkyl is understood in the context of this invention as Ci-salkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, or octyl; preferably is Ci-ealkyl like methyl, ethyl, propyl, butyl, pentyl, or hexyl; more preferably is Ci-4alkyl like methyl, ethyl, propyl or butyl.
Alkenyl is understood as meaning unsaturated, linear or branched hydrocarbons, which may be unsubstituted or substituted once or several times. It encompasses groups like e.g. -CH=CH-CH3. The alkenyl radicals are preferably vinyl (ethenyl), allyl (2-propenyl). Preferably in the context of this invention alkenyl is C2-io-alkenyl or C2-s-alkenyl like ethylene, propylene, butylene, pentylene, hexylene, heptylene or octylene; or is C2-6- alkenyl like ethylene, propylene, butylene, pentylene, or hexylene; or is C2-4-alkenyl, like ethylene, propylene, or butylenes. Alkynyl is understood as meaning unsaturated, linear or branched hydrocarbons, which may be unsubstituted or substituted once or several times. It encompasses groups like e.g. -C5C-CH3 (1-propinyl). Preferably alkynyl in the context of this invention is C2-10- alkynyl or C2-e-alkynyl like ethyne, propyne, butyene, pentyne, hexyne, heptyne, or octyne; or is C2-6-alkynyl like ethyne, propyne, butyene, pentyne, or hexyne; or is C2.4- alkynyl like ethyne, propyne, butyene, pentyne, or hexyne. In connection with alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyi), alkenyl, alkynyl and O-alkyI - unless defined otherwise - the term substituted in the context of this invention is understood as meaning replacement of at least one hydrogen radical on a carbon atom by halogen (F, CI, Br, I), -NRCRC\ -SRC, -S(0)Rc, -S(0)2Rc, -ORc, - C(0)ORc, -CN, -C(0)NRcRc\ haloalkyl, haloalkoxy or -OC1.6 alkyl, being Rc represented by R11 , R12, Ri3, (being Rc- represented by Rir, Ri2', R13'; being Rc- represented by Rn ··, Ri2 ", R13"; ) wherein Ri to Ri - and Rw, Rw are as defined in the description, and wherein when different radicals Ri to Ri4 ■■ and Rw, Rw' are present simultaneously in Formula I they may be identical or different.
Most preferably in connection with alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyi), alkenyl, alkynyl or O-alkyI, substituted is understood in the context of this invention that any alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyi), alkenyl, alkynyl or O-alkyl which, if substituted, is substituted with one or more of halogen (F, CI, Br, I), -ORc, -CN, -SRc,-S(0)Rc, -S(0)2Rc, haloalkyl, haloalkoxy, -NRCRC', or -OCi-6alkyl, being Rc represented by Rn , R12, R13, (being RC' represented by Ri v, Ri2', Ri3'; being Rc represented by Rir, R12", R13 ;), wherein Ri to Ri4- and Rw, Rw are as defined in the description, and wherein when different radicals Ri to Ri4- and Rw, Rw' are present simultaneously in Formula I, they may be identical or different.
More than one replacement on the same molecule and also on the same carbon atom is possible with the same or different substituents. This includes for example 3 hydrogens being replaced on the same C atom, as in the case of CF3, or at different places of the same molecule, as in the case of e.g. -CH(OH)-CH=CH-CHCl2.
In the context of this invention haloalkyl is understood as meaning an alkyl being substituted once or several times by a halogen (selected from F, CI, Br, I). It encompasses e.g. -CH2CI, -CH2F, -CHCI2, -CHF2, -CCI3, -CF3 and -CH2-CHCI2. Preferably haloalkyl is understood in the context of this invention as halogen- substituted Ci-4-alkyl representing halogen substituted C1-, C2-, C3- or C4-alkyl. The halogen-substituted alkyl radicals are thus preferably methyl, ethyl, propyl, and butyl. Preferred examples include -CH2CI, -CH2F, -CHCI2, -CHF2, and -CF3.
In the context of this invention haloalkoxy is understood as meaning an -O-alkyl being substituted once or several times by a halogen (selected from F, CI, Br, I). It encompasses e.g. -OCH2CI, -OCH2F, -OCHCI2, -OCHF2, -OCCI3, -OCF3 and - OCH2-CHCI2. Preferably haloalkyl is understood in the context of this invention as halogen-substituted -OCi-4-alkyl representing halogen substituted C1-, C2-, C3- or C4- alkoxy. The halogen-substituted alkyl radicals are thus preferably O-methyl, O-ethyl, O-propyl, and O-butyl. Preferred examples include -OCH2CI, -OCH2F, -OCHCI2, -
Figure imgf000021_0001
In the context of this invention cycloalkyi is understood as meaning saturated and unsaturated (but not aromatic) cyclic hydrocarbons (without a heteroatom in the ring), which can be unsubstituted or once or several times substituted. Furthermore, C3-4- cycloalkyl represents C3- or C4-cycloalkyl, C3-5-cycloalkyl represents C3-, C4- or C5- cycloalkyl, C3-6-cycloalkyl represents C3-, C4-, C5- or C6-cycloalkyl, C3-7-cycloalkyl represents C3-, C4-, C5-, C6- or C7-cycloalkyl, C3-8-cycloalkyl represents C3-, C4-, C5- , C6-, C7- or C8-cycloalkyl, C4-5-cycloalkyl represents C4- or C5-cycloalkyl, C4-6- cycloalkyi represents C4-, C5- or C6-cycloalkyl, C4-7-cycloalkyl represents C4-, C5-, C6- or C7-cycloalkyl, Cs-e-cycloalkyl represents C5- or C6-cycloalkyl and Cs-7-cycloalkyl represents C5-, C6- or C7-cycloalkyl. Examples are cyclopropyl, 2-methylcyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cycloheptyl, cyclooctyl, and also adamantly. Preferably in the context of this invention cycloalkyi is C3-8cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; or is C3-7cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; or is C3-6cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, especially cyclopentyl or cyclohexyl.
Aryl is understood as meaning 5 to 18 membered mono or polycyclic ring systems with at least one aromatic ring but without heteroatoms even in only one of the rings. Examples are phenyl, naphthyl, fluoranthenyl, fluorenyl, tetralinyl, indanyl, 9H-fluorenyl or anthracenyl radicals, which can be unsubstituted or once or several times substituted. Most preferably aryl is understood in the context of this invention as phenyl, naphthyl or anthracenyl, preferably is phenyl.
A heterocyclyl radical or group (also called heterocyclyl hereinafter) is understood as meaning 5 to 18 membered mono or poly heterocyclic ring systems, with at least one saturated or unsaturated ring which contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring. A heterocyclic group can also be substituted once or several times.
Examples include non-aromatic heterocyclyls such as tetrahydropyran, oxazepane, morpholine, piperidine, pyrrolidine as well as heteroaryls such as furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, thiazole, benzothiazole, indole, benzotriazole, carbazole and quinazoline.
Subgroups inside the heterocyclyls as understood herein include heteroaryls and non- aromatic heterocyclyls.
- the heteroaryl (being equivalent to heteroaromatic radicals or aromatic heterocyclyls) is an aromatic 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more rings of which at least one aromatic 5 to 18 membered ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is an aromatic 5 to 18 membered mono or polycyclic heterocyclic ring system of one or two rings of which at least one aromatic ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, benzothiazole, indole, benzotriazole, carbazole, quinazoline, thiazole, imidazole, pyrazole, oxazole, thiophene and benzimidazole;
- the non-aromatic heterocyclyl is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more rings of which at least one ring - with this (or these) ring(s) then not being aromatic - contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or two rings of which one or both rings - with this one or two rings then not being aromatic - contain/s one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepam, pyrrolidine, piperidine, piperazine, tetrahydropyran, morpholine, indoline, oxopyrrolidine, benzodioxane, oxetane, especially is benzodioxane, morpholine, tetrahydropyran, piperidine, oxopyrrolidine, oxetane and pyrrolidine.
Preferably in the context of this invention heterocyclyl is defined as a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring. Preferably it is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring.
An A/-containing heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains a nitrogen and optionally one or more further heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains a nitrogen and optionally one or more further heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepam, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzimidazole, indazole, benzothiazole, benzodiazole, morpholine, indoline, triazole, isoxazole, pyrazole, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, carbazole or thiazole. Preferred examples of heterocyclyls include oxetane, oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline, especially is pyridine, pyrazine, indazole, benzodioxane, thiazole, benzothiazole, morpholine, tetrahydropyran, pyrazole, imidazole, piperidine, thiophene, indole, benzimidazole, pyrrolo[2,3b]pyridine, benzoxazole, oxopyrrolidine, pyrimidine, oxazepane, oxetane and pyrrolidine.
In the context of this invention oxopyrrolidine is understood as meaning pyrrolidin-2- one.
In connection with aromatic heterocyclyls (heteroaryls), non-aromatic heterocyclyls, aryls and cycloalkyls, when a ring system falls within two or more of the above cycle definitions simultaneously, then the ring system is defined first as an aromatic heterocyclyl (heteroaryl) if at least one aromatic ring contains a heteroatom. If no aromatic ring contains a heteroatom, then the ring system is defined as a non-aromatic heterocyclyl if at least one non-aromatic ring contains a heteroatom. If no non-aromatic ring contains a heteroatom, then the ring system is defined as an aryl if it contains at least one aryl cycle. If no aryl is present, then the ring system is defined as a cycloalkyl if at least one non-aromatic cyclic hydrocarbon is present.
Preferably, the aryl is a monocyclic aryl. More preferably the aryl is a 5, 6 or 7 membered monocyclic aryl. Even more preferably the aryl is a 5 or 6 membered monocyclic aryl.
Preferably, the heteroaryl is a monocyclic heteroaryl. More preferably the heteroaryl is a 5, 6 or 7 membered monocyclic heteroaryl. Even more preferably the heteroaryl is a 5 or 6 membered monocyclic heteroaryl. Preferably, the non-aromatic heterocyclyl is a monocyclic non-aromatic heterocyclyl. More preferably the non-aromatic heterocyclyl is a 4, 5, 6 or 7 membered monocyclic non-aromatic heterocyclyl. Even more preferably the non-aromatic heterocyclyl is a 5 or 6 membered monocyclic non-aromatic heterocyclyl.
Preferably, the cycloalkyl is a monocyclic cycloalkyl. More preferably the cycloalkyl is a 3, 4, 5, 6, 7 or 8 membered monocyclic cycloalkyl. Even more preferably the cycloalkyl is a 3, 4, 5 or 6 membered monocyclic cycloalkyl.
In connection with aryl (including alkyl-aryl), cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkyl-heterocyclyl), substituted is understood - unless defined otherwise - as meaning substitution of the ring-system of the aryl or alkyl-aryl, cycloalkyl or alkyl-cycloalkyl; heterocyclyl or alkyl-heterocyclyl with one or more of halogen (F, CI, Br, I), -Rc ,-ORc, -CN, -N02 , -NRcRc, -C(0)ORc, NRcC(0)Rc , -C(0)NRcRc , - NRcS(0)2Rc , =0, -OCH2CH2ORc, -NRcC(0)NRcRc , -S(0)2NRcRC', -NRcS(0)2NRcRC", haloalkyl, haloalkoxy, -SRC, -S(0)Rc, -S(0)2Rc or -C(CH3)ORc; NRCRC\ with Rc, Rc and Rc- independently being either H or a saturated or unsaturated, linear or branched, substituted or unsubstituted Ci-e-alkyl; a saturated or unsaturated, linear or branched, substituted or unsubstituted Ci-e-alkyl; a saturated or unsaturated, linear or branched, substituted or unsubstituted -O-Ci-6-alkyl (alkoxy); a saturated or unsaturated, linear or branched, substituted or unsubstituted -S-Ci-6-alkyl; a saturated or unsaturated, linear or branched, substituted or unsubstituted -C(0)-Ci-6.alkyl-group; a saturated or unsaturated, linear or branched, substituted or unsubstituted -C(0)-0-Ci-6-alkyl-group; a substituted or unsubstituted aryl or alkyl-aryl; a substituted or unsubstituted cycloalkyl or alkyl-cycloalkyl; a substituted or unsubstituted heterocyclyl or alkyl-heterocyclyl, being Rc one of Rn, Ri2 or Ri4, (being RC' one of Rir, Ri2 or Ri4'; being Rc one of Rn-, Ri2" or Ri4";), wherein Ri to Ri4- and Rw, Rw are as defined in the description, and wherein when different radicals Ri to Ri4 and Rw, Rw are present simultaneously in Formula I they may be identical or different. Most preferably in connection with aryl (including alkyl-aryl), cycloalkyl (including alkyl- cycloalkyl), or heterocyclyl (including alkyl-heterocyclyl), substituted is understood in the context of this invention that any aryl, cycloalkyl and heterocyclyl which is substituted is substituted (also in an alkylaryl, alkylcycloalkyl or alkylheterocyclyl) with one or more of halogen (F, CI, Br, I), -Rc ,-ORc, -CN , -N02 , -NRCRC" , NRcC(0)Rc, - NRcS(0)2Rc' , =0, haloalkyl, haloalkoxy, or -C(CH3)ORc; being Rc one of Rn, Ri2orRi4, (being RC' one of Rir, Ri2' or Ri '; being Rc- one of R -, Ri2 orRi4";), wherein Ri to Ri4- and Rw, Rw' are as defined in the description, and wherein when different radicals Ri to Rn- and Rw, Rw are present simultaneously in Formula I they may be identical or different.
Moreover, in connection with cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl) namely non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), substituted is also understood - unless defined otherwise - as meaning substitution of the ring-system of the cycloalkyl yl-cycloalkyl; non- aromatic heterocyclyl or non aromatic alkyl-heterocyclyl with
Figure imgf000026_0001
(leading to a spiro structure) and/or =0.
Moreover, in connection with cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl) namely non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), substituted is also understood - unless defined otherwise - as meaning substitution of the ring-system of the cycloalkyl or alkyl-cycloalkyl; non- aromatic heterocyclyl or non aromatic alkyl-heterocyclyl is spirosubstituted or substituted with =0.
Moreover, in connection with cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl) namely non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), substituted is also understood - unless defined otherwise - as meaning substitution of the ring-system of the cycloalkyl or alkyl-cycloalkyl; non- aromatic heterocyclyl or non aromatic alkyl-heterocyclyl with =0.
A ring system is a system consisting of at least one ring of connected atoms but including also systems in which two or more rings of connected atoms are joined with "joined" meaning that the respective rings are sharing one (like a spiro structure), two or more atoms being a member or members of both joined rings.
In the context of this invention alkylaryl is understood as meaning an aryl group (see above) being connected to another atom through a Ci-6-alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times. Preferably alkylaryl is understood as meaning an aryl group (see above) being connected to another atom through 1 to 4 (-CH2-) groups. Most preferably alkylaryl is benzyl (i.e. -Chb-phenyl).
In the context of this invention alkylheterocyclyl is understood as meaning an heterocyclyl group (see above) being connected to another atom through a Ci-e-alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times. Preferably alkylheterocyclyl is understood as meaning a heterocyclyl group (see above) being connected to another atom through 1 to 4 (-CH2-) groups. Most preferably alkylheterocyclyl is -Ch -pyridine. In the context of this invention alkylcycloalkyl is understood as meaning an cycloalkyl group (see above) being connected to another atom through a Ci-e-alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times. Preferably alkylcycloalkyl is understood as meaning a cycloalkyl group (see above) being connected to another atom through 1 to 4 (-CH2-) groups. Most preferably alkylcycloalkyl is -CHb-cyclopropyl.
The term "leaving group" means a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as CI-, Br-, and I-, and sulfonate esters, such as tosylate (TsO-) or mesylate. The term "salt" is to be understood as meaning any form of the active compound used according to the invention in which it assumes an ionic form or is charged and is coupled with a counter-ion (a cation or anion) or is in solution. By this are also to be understood complexes of the active compound with other molecules and ions, in particular complexes via ionic interactions.
The term "physiologically acceptable salt" means in the context of this invention any salt that is physiologically tolerated (most of the time meaning not being toxic- especially not caused by the counter-ion) if used appropriately for a treatment especially if used on or applied to humans and/or mammals. These physiologically acceptable salts can be formed with cations or bases and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention - usually a (deprotonated) acid - as an anion with at least one, preferably inorganic, cation which is physiologically tolerated - especially if used on humans and/or mammals. The salts of the alkali metals and alkaline earth metals are particularly preferred, and also those with NH4, but in particular (mono)- or (di)sodium, (mono)- or (di)potassium, magnesium or calcium salts.
Physiologically acceptable salts can also be formed with anions or acids and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention as the cation with at least one anion which are physiologically tolerated - especially if used on humans and/or mammals. By this is understood in particular, in the context of this invention, the salt formed with a physiologically tolerated acid, that is to say salts of the particular active compound with inorganic or organic acids which are physiologically tolerated - especially if used on humans and/or mammals. Examples of physiologically tolerated salts of particular acids are salts of: hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid.
The compounds of the invention may be present in crystalline form or in the form of free compounds like a free base or acid. Any compound that is a solvate of a compound according to the invention like a compound according to general formula I defined above is understood to be also covered by the scope of the invention. Methods of solvation are generally known within the art. Suitable solvates are pharmaceutically acceptable solvates. The term "solvate" according to this invention is to be understood as meaning any form of the active compound according to the invention in which this compound has attached to it via non- covalent binding another molecule (most likely a polar solvent). Especially preferred examples include hydrates and alcoholates, like methanolates or ethanolates.
Any compound that is a prodrug of a compound according to the invention like a compound according to general formula I defined above is understood to be also covered by the scope of the invention. The term "prodrug" is used in its broadest sense and encompasses those derivatives that are converted in vivo to the compounds of the invention. Such derivatives would readily occur to those skilled in the art, and include, depending on the functional groups present in the molecule and without limitation, the following derivatives of the present compounds: esters, amino acid esters, phosphate esters, metal salts sulfonate esters, carbamates, and amides. Examples of well-known methods of producing a prodrug of a given acting compound are known to those skilled in the art and can be found e.g. in Krogsgaard-Larsen et al. "Textbook of Drug design and Discovery" Taylor & Francis (April 2002).
Any compound that is an /V-oxide of a compound according to the invention like a compound according to general formula I defined above is understood to be also covered by the scope of the invention.
Unless otherwise stated, the compounds of the invention are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by 13C- or 14C-enriched carbon or of a nitrogen by 15N-enriched nitrogen are within the scope of this invention. The compounds of formula (I) as well as their salts or solvates of the compounds are preferably in pharmaceutically acceptable or substantially pure form. By pharmaceutically acceptable form is meant, inter alia, having a pharmaceutically acceptable level of purity excluding normal pharmaceutical additives such as diluents and carriers, and including no material considered toxic at normal dosage levels. Purity levels for the drug substance are preferably above 50%, more preferably above 70%, most preferably above 90%. In a preferred embodiment it is above 95% of the compound of formula (I), or of its salts. This applies also to its solvates or prodrugs.
In a more particular embodiment the compound according to the invention of general Formula (I)
Figure imgf000030_0001
is a compound wherei
m is 0, 1 or 2; r is 0, 1 or 2; n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3; X is a bond or - Y is selected from -O- and -S-;
W is-C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6alkynyl, Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
Ri is selected from substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in Ri if substituted, is substituted with one or more substituent/s selected from halogen, -Rn , -ORn , -NO2, -NRn Ri r, - NRi i C(0)Ri r, -NRnS(0)2Rn , -S(0)2NRn Ri r, -NRnC(0)NRn Ri r , -SRn , - S(0)Ri i , S(0)2Ri i , -CN, haloalkyl, haloalkoxy, -C(0)ORu , -C(0)NRn Ri r, -
OCH2CH2OR11 , -NRi iS(0)2NRi i R11 and -C(CH3)2ORn ;
wherein the alkyl, alkenyl or alkynyl in Ri , if substituted, is substituted with one or more substituent/s selected from -ORn , halogen, -CN, haloalkyl, haloalkoxy and -
wherein Rn , Ri r and Rn are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted unsubstituted heterocyclyl, wherein said cycloalkyi, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, - Ri2Ri2', - NR12C(0)Ri2', -NRi2S(0)2 i2-, -S(0)2NRi2Ri2-, -NRi2C(0)NRi2-Ri2", -SR12, -S(0)Ri2, -S(0)2Ri2, -CN, haloalkyl, haloalkoxy, -C(0)ORi2, -C(0)NRi2Ri2-, -OCH2CH2ORi2, - NRi2S(0)2NRi2 Ri2" and -C(CH3)2ORi2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, Ri2 and R12" are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl ;
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2.6 alkenyl, substituted or unsubstituted C2-e alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R4 and R4' are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R4 and R4\ may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyi;
R4 and R4 - are independently selected from hydrogen, substituted or unsubstituted C 6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2 alkynyl; alternatively, R4- and R4", may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R13 and Ri3' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;
the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -OR14, -NO2, -NR14R14', -NRi4C(0)Ri4', - NR14S(0)2Ri4', -S(0)2NR14Ri4', - NRi4C(0)NRi -Ri4», -SRM , -S(0)Ri4, S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi4, -C(0)NRi4Ri4-, -OCH2CH2ORi4, -NRi4S(0)2NRi4'Ri4"
Figure imgf000033_0001
wherein R14, Rib and Ri4- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
These preferred compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein m is 0, 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein n is 0, 1 , 2 or 3; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general f Formula (I) is a compound wherein p is 1 , 2 or 3; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein q is 1 , 2 or 3; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein r is 0, 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general f Formula (I) is a compound wherein
W is -C(RwRw)- or -N(RW)-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein
W is-C(RwR wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-e alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Figure imgf000036_0001
wherein Rw is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-e alkenyl, substituted or unsubstituted C2-6 alkynyl, Rw' is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-e alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein
Ri is selected from substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein Ri is substituted or unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein
R2 is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-e alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein is selected from substituted or unsubstituted C1-6 alkyl and substituted or unsubstituted aryl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcydoalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl and substituted or unsubstituted alkylaryl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
R4 and R4 are independently selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
R4 and R4' are independently selected from hydrogen and substituted or unsubstituted C1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
R4 and R4 are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
R4 and R4' may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
R4- and R4 - are independently selected from hydrogen, substituted or unsubstituted Ci- 6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein R4- and R4- are independently selected from hydrogen and substituted or unsubstituted Ci-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein R4" and R4 - are both substituted or unsubstituted Ci-e alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
R4" and R - may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein R5 and R5' are independently selected from halogen, -Rn , -ORn , -N02, -NRn Ri r, - NRn C(0)Ri r, -NRn S(0)2Ri r, -S(0)2NRn Ri r, -NRn C(0)NRi rRn , -SRn , -S(0)Rn , - S(0)2Ri i , -CN, haloalkyl, haloalkoxy, -C(0)ORn , -C(0)NRn Rn , -OCH2CH2ORn , - NR S(0)2NRi rRi and -C(CH3)2ORn ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Rs and R5' are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein Rw is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C^e alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Rw is selected from hydrogen and substituted or unsubstituted Ci-e alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Rw' is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C^e alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Rw is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Ri i , Ri i and Rn- are independently selected from hydrogen, unsubstituted Ci-e alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
R12, Ri2' and Ri are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Ri3 and R13' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-& alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Ri3 is unsubstituted Ci-6 alkyl, unsubstituted C2-e alkenyl, and unsubstituted C2-e alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein
Ri4, Ri4' and Ri4- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the compound according to the invention of general Formula (I), is a compound wherein m is 0, 1 or 2; and/or
r is 0, 1 or 2; and/or
n is 0, 1 , 2 or 3; and/or
p is 1 , 2 or 3; and/or
q is 1 , 2 or 3; and/or
X is a bond or -0-; and/or
Y is selected from -O- and -S-; and/or
W is -C(RwRw')- or -N(RW)-; and/or
w is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C^ alkenyl, substituted or unsubstituted C^ alkynyl, wherein the Ci-e alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C1-6 alkyl is methyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;
and/or
Rw is selected from hydrogen, substituted or unsubstituted O-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; wherein the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or
Ri is selected from substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline; preferably the heterocyclyl is pyridine;
and/or
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C1-6 alkyl is isopropyl or isobutyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; more preferably the aryl is phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline; and/or R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; wherein the alkyl is C1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the alkyl is methyl; and/or the Ci-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C1-6 alkyl is methyl, ethyl or isopentyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyi is C3-8 cycloalkyi like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyi like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyi like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; more preferably the aryl is phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline; and/or
R4 and R4 are independently selected from hydrogen, substituted or unsubstituted d-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; wherein the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the C1-6 alkyl is methyl;
and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or
R4 and R-r may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; wherein the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or
R4" and R4 - are independently selected from hydrogen, substituted or unsubstituted Ci. 6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; wherein the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the Ci_e alkyl is methyl;
and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or
R4- and R4- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; wherein the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cydopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cydopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cydopentyl or cyclohexyl; and/or
R5 and R5' are independently selected from halogen, -Rn, -ORn, -NO2, -NRnRir, - NRiiC(0)Rir, -NRnS(0)2 ir, -S(0)2NRnRir, -NRnC(0)NRirRir, -SRn , -S(0)Rn, - S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnRir, -OCH2CH2ORn, - NRnS(0)2NRii Rir and -C(CH3)2ORn; wherein the alkyl is Ci-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the alkyl is methyl; and/or Ri i , Ri i and Rn are independently selected from hydrogen, unsubstituted C1-6 alkyi, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl. wherein the C1-6 alkyi is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;
and/or
R12, Ri2' and Ri2- are independently selected from hydrogen, unsubstituted C1-6 alkyi, unsubstituted C2-e alkenyl and unsubstituted C2-e alkynyl ; wherein
the C1-6 alkyi is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, preferably, C1-6 alkyi is ethyl ; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;
and/or
Ri3 and R13' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl; wherein the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the C1-6 alkyl is isopropyl;
and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or
Ri4, Ri4' and Ri4- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; wherein the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-s cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Rw as defined in any of the embodiments of the present invention, the Ci-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C1-6 alkyl is methyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in RW' as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the Ci-e alkyl is methyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Ri as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline; preferably the heterocyclyl is pyridine; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R2 as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C1-6 alkyl is isopropyl or isobutyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; more preferably the aryl is phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R3 as defined in any of the embodiments of the present invention, the alkyl is Ci-e alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the alkyl is methyl; and/or the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the Ci-6 alkyl is methyl, ethyl or isopentyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-s cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; more preferably the aryl is phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R4 and R4' as defined in any of the embodiments of the present invention, the Ci-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the C1-6 alkyl is methyl;
and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R4 and R4- as defined in any of the embodiments of the present invention, the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R4 and R4- as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the Ci_s alkyl is methyl;
and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R4- and R4- as defined in any of the embodiments of the present invention, the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R5 and R5 as defined in any of the
embodiments of the present invention, the alkyl is C1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the alkyl is methyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Rn , Ri and Rn- as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-e -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R12, R12' and R12" as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, preferably, Ci-6 alkyl is ethyl ; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R13 and R13' as defined in any of the embodiments of the present invention,
the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the Ci-6 alkyl is isopropyl;
and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R14, Ri4' and Ri - as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-e cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein m is 0, 1 or 2; preferably m is 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein r is 0, 1 or 2; preferably r is 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein n is 0, 1 , 2 or 3; preferably n is 0 or 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein p is 1 , 2 or 3; preferably p is 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein q is 1 , 2 or 3; preferably q is 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein
Y is selected from -O- and -S-; preferably, Y is -0-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein
W is -C(RwRw)- or -N(RW)-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (Γ)
Figure imgf000073_0001
(I ),
wherein m is 0, 1 or 2; r is 0, 1 or 2; n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3; X is a bond or -0-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, Rw' is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
Ri is selected from substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
R2 is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-e alkenyl, substituted or unsubstituted C2-e alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R4 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-e alkenyl and substituted or unsubstituted C2-e alkynyl; alternatively, R4 and R4' may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyi; R.4" and R4 are independently selected from hydrogen, substituted or unsubstituted Ci- 6 alkyl, substituted or unsubstituted C2-e alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R ■ and R4- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (Γ)
Figure imgf000075_0001
wherein m is 0, 1 or 2; r is 0, 1 or 2; n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3;
X is a bond or -0-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
Ri is selected from substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in Ri if substituted, is substituted with one or more substituent/s selected from halogen, -Rn, -ORn, -NO2, -NR Riv, - NR C(0)Rir, -NRnS(0)2Rir, -S(0)2NRnRir, -NR C(0)NRn-Rir , -SRn , -
S(0)Rii, S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnR1 v, - OCH2CH2OR11 , -NRnS(0)2NRirRi and -C(CH3)2ORn;
wherein the alkyl, alkenyl or alkynyl in Ri, if substituted, is substituted with one or more substituent/s selected from -ORn, halogen, -CN, haloalkyl, haloalkoxy and - NRnRir; wherein R-n, Rir and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyi, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12', - NRi2C(0)Ri2-, -NR12S(0)2Ri2', -S(0)2NRi2Riz, -NRi2C(0)NRi2 Ri2", -SR12, -S(0)R12,
-S(0)2Ri2, -CN, haloalkyl, haloalkoxy, -C(0)ORi2, -C(0)NRi2Ri2 , -OCH2CH2OR12, - NRi2S(0)2NRi2'Ri2" and -C(CH3)2ORi2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, R12' and 12" are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-e alkynyl ;
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2.e alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R4 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-e alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R4 and R4' may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyi; R4- and R4- are independently selected from hydrogen, substituted or unsubstituted Ci- 6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R4- and R4- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13 ; wherein R13 and Ri3' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;
the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyi, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -Ri4, -ORi , -NO2, -NRi Ri4', -NRi4C(0)Ri4', - NRi4S(0)2Ri4', -S(0)2NRi4Ri4-, - NRi4C(0)NRi4-Ri4", -SRi4 , -S(0)Ri4, S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi4, -C(0)NRi Ri -, -OCH2CH2OR14, -NRi S(0)2NR Ri -
Figure imgf000078_0001
wherein Ri4, Ri4 and Ri4 ■■ are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-e alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (I2')
Figure imgf000079_0001
wherein
wherein
m is 0, 1 or 2;
r is 0, 1 or 2;
n is 0, 1 , 2 or 3;
p is 1 , 2 or 3;
q is 1 , 2 or 3;
X is a bond or -0-;
W is -C(RwRw)- or -N(Rw)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-e alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2.6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2.6 alkenyl, substituted or unsubstituted C2.6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R4 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2.6 alkynyl; alternatively, R4 and R4' may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyi;
R " and R4 - are independently selected from hydrogen, substituted or unsubstituted Ci. 6 alkyl, substituted or unsubstituted C2-e alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R4- and R4 ■ may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyi; R-5 and R5 are independently selected from halogen, -R , -ORn, -NO2, -NRnRir, - NRiiC(0)Rii , -NRiiS(0)2Rii , -S(0)2NRuRir, -NRnC(0)NRi Rir, -SRn , -S(0)Rn, - S(0)2Rn, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnRir, -OCH2CH2ORn, - NRiiS(0)2NRirRn" and -C(CH3)2ORn; and Rn, Rn and Rn-are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl.
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (I2')
Figure imgf000081_0001
d2'),
wherein m is 0, 1 or 2; r is 0, 1 or 2; n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3; X is a bond or -0-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted C -6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted Ci.6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -N R12R12 , NRi2C(0)Ri2', -NRi2S(0)2Ri2', -S(0)2NRi2Ri?, -NRi2C(0)NRi2-Ri2 », -SR12, -S(0)Ri2, S(0)2Ri 2, -CN , haloalkyl, haloalkoxy, -C(0)OR12, -C(0)N Ri2Ri2-, -OCH2CH2ORi2, - N Ri2S(0)2N Ri 2'Ri 2 " and C(CH3)20Ri2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, Ri2 and Ri2- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl ; R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R4 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R4 and R4- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyi;
R4- and R4-are independently selected from hydrogen, substituted or unsubstituted Ci- 6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2.6 alkynyl; alternatively, R4 and R4- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyi;
R5 and R5 are independently selected from halogen, -Rn , -ORn , -N02, -NRn Ri r, - NRii C(0)Ri r, -NRi iS(0)2Ri v, -S(0)2NRn Rn , -NRn C(0)NRn Rn-, -SRn , -S(0)Rn , - S(0)2Ri i , -CN, haloalkyl, haloalkoxy, -C(0)ORn , -C(0)NRn Ri r, -OCH2CH2ORn , - NRn S(0)2NRi rRi i" and -C(CH3)2ORn ; and R11 , Ru and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl. the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13 ; wherein R13 and R13' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;
the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -ORi4, -N02, -NRi4Ri4', NRi4C(0)Ri4', - NR14S(0)2R14', -S(0)2NR14Rl4', - NR14C(0)NRi4 Ri4-, -SRH , -S(0)Ri4, S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi , -C(0)NR14Ri4', -OCH2CH2ORi4, -NRi S(0)2NRi4 Ri4-
Figure imgf000084_0001
wherein Ri4, Rib and Ri are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2.6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (I3')
Figure imgf000085_0001
wherein m is 0, 1 or 2; r is 0, 1 or 2; n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3;
X is a bond or -0-; W is -C(RwRw)- or -N(Rw)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted Ci -6 alkyl, substituted or unsubstituted C2-e alkenyl and substituted or unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyi, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12', NRi2C(0)Ri2-, -NRi2S(0)2Ri2', -S(0)2NR12Ri2 , -NRi2C(0)NRi2 Ri2", -SR12, -S(0)Ri2,
S(0)2Ri2, -CN, haloalkyl, haloalkoxy, -C(0)ORi2, -C(0)NRi2Ri2 , -OCH2CH2OR12, - NRi2S(0)2NRi2'Ri2" and C(CH3)2ORi2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, Ri2- and R12■ are independently selected from hydrogen, unsubstituted Ci-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2.e alkynyl ;
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R5 and R5' are independently selected from halogen, -Rn , -ORn , -NO2, -NRn Ri r, - NRi i C(0)Ri r, -NRn S(0)2Ri r, -S(0)2NRn Rn-, -NRn C(0)NRi rR , -SRn , -S(0)Rn , - S(0)2Ri i , -CN, haloalkyl, haloalkoxy, -C(0)ORn , -C(0)NRn Ri r, -OCH2CH2ORn , - NRi i S(0)2NRi i Rn- and -C(CH3)2ORn ; and Rn , Rn and Rn- are independently selected from hydrogen, unsubstituted Ci.6 alkyl, unsubstituted C2-e alkenyl and unsubstituted C2-6 alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (I3')
Figure imgf000087_0001
(I3'),
wherein m is 0, 1 or 2; r is 0, 1 or 2; n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3;
X is a bond or -0-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2.6 alkynyl,
Rw is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2.6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyi, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -Ri2, -OR12, -N02, -NRi2Ri , NRi2C(0)Ri2', -NRi2S(0)2Ri2', -S(0)2NRi2R12., -NRi2C(0)NRi2 Ri2 -, -SRi2, -S(0)Ri2, S(0)2Ri2, -CN, haloalkyl, haloalkoxy, -C(0)OR12, -C(0)NRi2Ri2', -OCH2CH2OR 2, - NRi2S(0)2NRizRir and C(CH3)2ORi2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, -
wherein Ri2, Ri2 and Ri2- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-e alkynyl ;
R3 is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-e alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; R5 and R5 are independently selected from halogen, -Rn , -ORn , -NO2, -NRnRn , - NRn C(0)Ri r, -NRn S(0)2Ri r, -S(0)2NRn Rn , -NRn C(0)NRn Ri r , -SRn , -S(0)R , - S(0)2Ri i , -CN, haloalkyl, haloalkoxy, -C(0)ORn , -C(0)NRn Ri r, -OCH2CH2ORn , - NRi i S(0)2NRi rRi and -C(CH3)2ORn ; and Rn , Ru and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-e alkynyl.
the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R13 and R13' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-e alkynyl;
the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -ORi , -N02, -NRi4Ri4',
Figure imgf000089_0001
- NRi4S(0)2Ri4 , -S(0)2NRi4Ri4 , - NRi4C(0)NR14 Ri4' , -SRi4 , -S(0)Ri4, S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)OR14, -C(0)NR14R14 , -OCH2CH2ORi4, -NRi4S(0)2NRi4 R14-
Figure imgf000089_0002
wherein Ri4, Ri4 and Ru- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2.6 alkenyl, unsubstituted C2-e alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (I4')
Figure imgf000090_0001
n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3; X is a bond or -0-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R5 and R5' are independently selected from halogen, -Rn , -ORn , -NO2, -NRn Ri r, - NRi i C(0)Ri r, -NR S(0)2Ri r, -S(0)2NRn Ri r, -NRnC(0)NRirRn , -SRn , -S(0)Rn , - S(0)2Ri i , -CN , haloalkyl, haloalkoxy, -C(0)ORn , -C(0)NRn Rn , -OCH2CH2ORn , - NRn S(0)2NRn R11 and -C(CH3)2ORi i ; and R11 , Rn and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (I4')
Figure imgf000092_0001
(Ι4'),
wherein n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3;
X is a bond or -0-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-e alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-e alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-e alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyi, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12', NRi2C(0)Ri2', -NRi2S(0)2Ri2', -S(0)2NRi2Ri2-, -NRi2C(0)NRi2-Ri2 », -SR12, -S(0)Ri2, S(0)2Ri2, -CN, haloalkyl, haloalkoxy, -C(0)ORi2, -C(0)NRi2Ri2-, -OCH2CH2OR12, - NRi2S(0)2NRi2 Ri2" and C(CH3)2ORi2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -ORi2, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, Ri2 and Ri2- are independently selected from hydrogen, unsubstituted
C1-6 alkyl, unsubstituted C2-e alkenyl and unsubstituted C2.6 alkynyl ;
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aikylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R5 and R5' are independently selected from halogen, -Rn , -ORn , -N02, -NRn Ri , - NRi i C(0)Ri r, -NRnS(0)2Ri r, -S(0)2NRn Ri v, -NRn C(0)NR Ri r, -SRn , -S(0)Rn , - S(0)2Rii , -CN, haloalkyl, haloalkoxy, -C(0)ORn , -C(0)NRn Ri r, -OCH2CH2ORn , - NRi i S(0)2NRi i R11" and -C(CH3)2ORn ; and R11 , Ru and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-e alkenyl and unsubstituted C2-6 alkynyl.
the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R13 and R13 are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;
the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -ORi4, -N02, -NRi4Ri4 , NRi4C(0)Ri4', - NRi4S(0)2Ri4', -S(0)2NRi4Ri4', - NRi4C(0)NRi4 Ri4-, -SRU , -S(0)Ri4, S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi , -C(0)NRi4Ri4', -OCH2CH2ORi4, -NRi S(0)2NRi4 Ri4 '
Figure imgf000094_0001
wherein Ri4, Ri4 and R - are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (I5')
Figure imgf000095_0001
(I5') ,
wherein q is 1 , 2 or 3;
X is a bond or -0-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-e alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R5 and Rs' are independently selected from halogen, -Rn, -ORn, -NO2, -NRnRir, - NRiiC(0)Rir, -NR,iS(0)2Riv, -S(0)2NRnRir, -NRnC(0)NRn Ri , -SRn , -S(0)Rn, - S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnRir, -OCH2CH2ORn, - NRiiS(0)2NRirRir and -C(CH3)2ORn; and R11, Ru and Rn-are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (I5')
Figure imgf000096_0001
(I5')- wherein q is 1 , 2 or 3;
X is a bond or -0-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12', NRi2C(0)Rir, -NR12S(0)2Ri2', -S(0)2NRi2Ri2', -NRi2C(0)NR12 Ri2", -SR12, -S(0)R12,
S(0)2Ri2, -CN, haloalkyl, haloalkoxy, -C(0)OR12, -C(0)NRi2Ri2', -OCH2CH2ORi2, - NRi2S(0)2NRi2'Ri2" and C(CH3)2ORi2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -ORi2, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, Rib and Ri2 are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-e alkynyl ;
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
Rs and R5' are independently selected from halogen, -Rn, -ORn, -NO2, -NRnRir, - NRiiC(0)Rir, -NR S(0)2Rir, -S(0)2NRnRn■, -NRiiC(0)NRirRii", -SRn , -S(0)R , - S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnRn-, -OCH2CH2OR11, - NRiiS(0)2NRirRn" and -C(CH3)2ORn; and R11, R - and Rn- are independently selected from hydrogen, unsubstituted Ci-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2.e alkynyl.
the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NRi3Ri3'; wherein R13 and Ri3' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2.e alkynyl;
the aryl, heterocyclyl or cycloalkyi, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyi, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -Ri4, -OR , -N02, -NRi Ri4', NRi4C(0)Ri4', - NRi4S(0)2Ri4', -S(0)2NRi4Ri4-, - NR14C(0)NRi4'Ri4", -SR14 , -S(0)Ri4, S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi4, -C(0)NRi4Ri4 , -OCH2CH2ORi4, -NRi S(0)2NRi Ri -
Figure imgf000098_0001
wherein Rn, Ri4 and Ri - are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-e alkynyl, unsubstituted aryl, unsubstituted cycloalkyi and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (l5a')
Figure imgf000099_0001
wherein q is 1 , 2 or 3;
X is a bond or -0-;
Rw is selected from hydrogen, substituted or unsubstituted O-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R5 and R5' are independently selected from halogen, -Rn, -ORn, -N02, -NRnRir, NRnC(0)Rir, -NRnS(0)2Rir, -S(0)2NRnRir, -NRnC(0)NRirRir, -SRn , -S(0)Rn, S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnRi r, -OCH2CH2ORn, NRiiS(0)2NRirRi and -C(CH3)2ORn; and R11 , Ru and R - are independently selected from hydrogen, unsubstituted Ci alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2.6 alkynyl.
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula the compound is a compound of Formula (l5a')
Figure imgf000101_0001
wherein q is 1 , 2 or 3;
X is a bond or -0-;
Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyi, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12', NRi2C(0)Ri2-, -NRi2S(0)2Ri2', -S(0)2NRi2Ri2-, -NRi2C(0)NRi2'Ri2", -SR12, -S(0)Ri2, S(0)2Ri2, -CN, haloalkyl, haloalkoxy, -C(0)OR12, -C(0)NRi2Ri2-, -OCH2CH2ORi2, - NRi2S(0)2NRi2 Ri2" and C(CH3)20Ri2; wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, Ri2- and Ri2- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-e alkynyl ;
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R5 and R5 are independently selected from halogen, -Rn, -ORn, -NO2, -NRnRir, NRiiC(0)Rir, -NRnS(0)2Rir,
Figure imgf000102_0001
-NRnC(0)NRi Rir, -SRn , -S(0)Rn, S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnRi r, -OCH2CH2OR11 , NRiiS(0)2NRirRii" and -C(CH3)2ORn; and R11 , Ru and R - are independently selected from hydrogen, unsubstituted Ci alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2.6 alkynyl.
the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R13 and R13' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;
the aryl, heterocyclyl or cycloalkyi, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyi, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -Ri4, -OR14, -NO2, -NR14R14', NRi4C(0)Ri4', - NRi4S(0)2Ri4 , -S(0)2NRi Ri4-, - NR14C(0)NRi4 R14 , -SR14 , -S(0)Ri , S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi4,
Figure imgf000103_0001
-OCH2CH2ORi4, -NRi S(0)2NRi Ri4-
Figure imgf000103_0002
wherein Ri4, Rib and R - are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2.6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (l5b')
Figure imgf000103_0003
wherei q is 1 , 2 or 3;
X is a bond or -0-;
Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw' is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted unsubstituted heterocyclyl,
R3 is selected from hydrogen, substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R5 and R5' are independently selected from halogen, -Rn , -ORn , -NO2, -NRn Ri r, - NRi i C(0)Ri r, -NRn S(0)2Ri r, -S(0)2NRn Ri r, -NR C(0)NRn Rn-, -SRn , -S(0)Rn , - S(0)2Ri i , -CN , haloalkyl, haloalkoxy, -C(0)ORn , -C(0)NRn Ri r, -OCH2CH2OR11 , - NRn S(0)2NRi rRi and -C(CH3)2ORn ; and R11 , Ru and Rn- are independently selected from hydrogen, unsubstituted Ci-e alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), the compound is a compound of Formula (l5b')
Figure imgf000105_0001
(l5b'),
wherein q is 1 , 2 or 3;
X is a bond or
Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted unsubstituted C^e alkenyl, substituted or unsubstituted C2-6 alkynyl,
Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; R2 is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2.6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyi, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -Ri2, -ORi2, -N02, -NRi2Ri2', NRi2C(0)Ri2', -NR12S(0)2Ri2', -S(0)2NRi2Ri2', -NRi2C(0)NRi2-Ri2 », -SR12, -S(0)Ri2, S(0)2Ri2, -CN, haloalkyl, haloalkoxy, -C(0)ORi2, -C(0)NRi2Riz, -OCH2CH2ORi2, - NRi2S(0)2NRi2 Ri2" and C(CH3)2ORi2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -ORi2, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, Riz and Ri2- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl ;
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2.6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R5 and R5' are independently selected from halogen, -Rn , -ORn , -N02, -NRn Ri r, - NRi i C(0)Ri r, -NRnS(0)2Ri r, -S(0)2NRi i R1 v, -NRn C(0)NRn Rn , -SRn , -S(0)Rn , - S(0)2Ri i , -CN, haloalkyl, haloalkoxy, -C(0)OR , -C(0)NRn R , -OCH2CH2ORn , - NRn S(0)2NRi i Rn · and -C(CH3)2ORn ; and Rii , Rn and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl.
the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R13 and Ri3' are independently selected from hydrogen, unsubstituted Ci.6 alkyl, unsubstituted C2.6 alkenyl, and unsubstituted C2-6 alkynyl;
the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -OR14, -N02, -NRMRW, NRi4C(0)Ri ', - NRi4S(0)2Ri4', -S(0)2NRi4R14', - NRi4C(0)NR14'Ri4", -SR14 , -S(0)Ri4l S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi , -C(0)NRi4Ri4', -OCH2CH2ORi4, -NRi4S(0)2NRi4 R1 - and C(CH3)2OR14;
wherein Ri4, Ri4 and Ri4- are independently selected from hydrogen, unsubstituted Ci-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-e alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another preferred embodiment of the invention according to general Formula (I), th compound is a compound of Formula (Γ),
Figure imgf000108_0001
(Γ), a compound of Formula (la)
Figure imgf000108_0002
(I2'), a compound of Formula (I3')
Figure imgf000109_0001
a compound of Formula (I5')
Figure imgf000110_0001
109 (|5b.)
wherein R5 and R5 are independently selected from halogen, -Rn, -ORn, -NO2, -NR11 R11', -NRnC(0)Rir, -NRnS(0)2Rn , -S(0)2NRnRi r, -NRnC(0)NRn Rn-,
-SR11 , -S(0)Rii, -S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, - C(0)NRnRi , -OCH2CH2OR11 , -NRnS(0)2NRi rRn" and -C(CH3)2ORn; and Rn, Rir and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl. optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a preferred embodiment m is 1.
In a preferred embodiment r is 1.
In a preferred embodiment n is 0 or 1.
In a preferred embodiment p is 1 or 2.
In a preferred embodiment q is 0 or 1.
In a preferred embodiment Y is -0-.
In a preferred embodiment
X is a bond or -0-.
In a preferred embodiment
W is -C(RwRw')- or -N(Rw)-.
In a preferred embodiment
Rw is hydrogen or substituted or unsubstituted methyl, preferably hydrogen or unsubstituted methyl.
In a preferred embodiment
Rw- is hydrogen.
In a preferred embodiment
Rw is hydrogen or substituted or unsubstituted methyl, preferably hydrogen or unsubstituted methyl, while RW' is hydrogen.
In a preferred embodiment
Rw and RW' are both hydrogen.
In a preferred embodiment,
Ri is a substituted or unsubstituted pyridine, preferably unsubstituted pyridine.
In a preferred embodiment R2 is substituted or unsubstituted group selected from isopropyl, isobutyl and phenyl, more preferably an unsubstituted group selected from isopropyl, isobutyl and phenyl.
In a preferred embodiment R3 is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl and isopentyl; preferably hydrogen or an unsubstituted group selected from methyl, ethyl and isopentyl.
In a preferred embodiment R4 is hydrogen.
In a preferred embodiment R4' is hydrogen.
In a preferred embodiment R4" is hydrogen.
In a preferred embodiment R4- is hydrogen.
preferred embodiment R4 and R4 are both hydrogen.
In a preferred embodiment R4" and R4- are both hydrogen.
In a preferred embodiment
R4" and R - are both substituted or unsubstituted methyl; more preferably R4 · and R4- are both unsubstituted methyl.
In a preferred embodiment
R4 and R4' are both hydrogen, while R4- and R4- are both substituted or unsubstituted alkyl.
In a preferred embodiment R and R - are both hydrogen, while R4- and R4 - are both substituted or unsubstituted (Ci-e)-alkyl.
In a preferred embodiment
R4 and R4' are both hydrogen, while R4- and R - are both substituted or unsubstituted methyl; more preferably while R4- and R4 - are both unsubstituted methyl.
In the above 3 preferred embodiments it has to be understood that both enantiomers based on the optically active C atom of the compound at the 3- position of the tetrahydropyran or tetrahydrothiopyrane are preferred. In a preferred embodiment
R4- and R4 - are both hydrogen, while R4 and R4' are both substituted or unsubstituted alkyl.
In a preferred embodiment
R4" and R4 - are both hydrogen, while R4 and R4' are both substituted or unsubstituted (Ci-e)-alkyl.
In a preferred embodiment
R4" and R4 - are both hydrogen, while R4 and R4 are both substituted or unsubstituted methyl; more preferably while R4 and R4' are both unsubstituted methyl.
In the above 3 preferred embodiments it has to be understood that both enantiomers based on the optically active C atom of the compound at the 3- position of the tetrahydropyran or tetrahydrothiopyrane are preferred.
In a preferred embodiment 5 is hydrogen. In a preferred embodiment R5' is hydrogen.
In a preferred embodiment R5 and R5 are both hydrogen. In a preferred embodiment
R13 IS substituted or unsubstituted isopropyl, preferably unsubstituted isopropyl.
In a preferred further embodiment, the compounds of the general Formula (I) are selected from
Figure imgf000116_0001
(4-(3-(benzyl(2-isopropoxyethyl)amino)propyl)-2,2- dimethyltetrahydro-2/-/-pyran-4-yl)(pyridin-2- yl)methanone
(4-((2-(lsopentylamino)ethyl)(methyl)amino)-2,2- dimethyltetrahydro-2 - -pyran-4-yl)(pyridin-2- yl)methanone
Figure imgf000117_0001
(4-(3-(isopentylamino)propyl)-2,2-dimethyltetrahydro- 2/-/-pyran-4-yl)(pyridin-2-yl)methanone
Figure imgf000117_0002
(4-(3-((2-isopropoxyethyl)amino)propyl)-2,2- dimethyltetrahydro-2/-/-pyran-4-yl)(pyridin-2-
N o yl)methanone
(4-((2-(isopentyl(methyl)amino)ethyl)(methyl)amino)-
2,2-dimethyltetrahydro-2H-pyran-4-yl)(pyridin-2- yl)methanone
Figure imgf000117_0003
(4-(3-(isopentyl(methyl)amino)propyl)-2,2-
8 dimethyltetrahydro-2/-/-pyran-4-yl)(pyridin-2- yl)methanone
/
(4-(3-((2-isopropoxyethyl)(methyl)amino)propyl)-2,2-
9 dimethyltetrahydro-2/-/-pyran-4-yl)(pyridin-2-
N 0 yl)methanone
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a preferred embodiment of the compound according to the invention of general Formula (I), Ri is selected from substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in Ri if substituted, is substituted with one or more substituent/s selected from halogen, -Rn , -ORn , -NO2, -NR Ri r,
NRi i C(0)Ri r, -NRn S(0)2Ri r, -S(0)2NRn Ri r, -NRn C(0)NRn'Ri r, -SRn , - S(0)Ri i , S(0)2Ri i , -CN , haloalkyl, haloalkoxy, -C(0)ORn , -C(0)NRn Ri r, - OCH2CH2OR11 , -NRn S(0)2NRi rRn " and C(CH3)2ORn ; wherein the alkyl, alkenyl or alkynyl in Ri , if substituted, is substituted with one or more substituent/s selected from -ORu , halogen, -CN, haloalkyl, haloalkoxy and - NR Ri r; wherein Rn , Ru and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another embodiment of the invention the compound of general Formula (I),
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12', NR12C(0)Ri2 , -NRi2S(0)2Ri2 , -S(0)2NRi2Ri2', -NRi2C(0)NRi2'Ri2", -SR12, -S(0)Ri2, S(0)2Ri2, -CN , haloalkyl, haloalkoxy, -C(0)ORi2, -C(0)NRi2Ri2', -OCH2CH2OR12, -
NRi2S(0)2 Ri2'Ri2" and C(CH3)2ORi2;
wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, -
wherein R12, Ri2 and Ri2- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another embodiment of the invention the compound of general Formula (I), the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and - R13R13'; wherein R13 and Ri3' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In another embodiment of the invention the compound of general Formula (I), the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -ORi4, -N02, -NRi Ri4',
Figure imgf000120_0001
- NRi4S(0)2Ri4', -S(0)2NRi4Ri4-, - NRi4C(0)NRi4 Ri4", -SR14 , -S(0)Ri4, S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi , -C(0)NRi4Ri4', -OCH2CH2ORi4, -NRi S(0)2NRi Ri "
Figure imgf000120_0002
wherein Ri , Ri4 and Ri4- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a preferred embodiment of the compound according to the invention of general Formula (I) and in relation to Ri of any of the embodiments of the present invention, the cycloalkyl, aryl or heterocyclyl in Ri if substituted, is substituted with one or more substituent/s selected from halogen, -Rn, -ORn, -N02, -NRnRn-, NRnC(0)Rir, - NRiiS(0)2Rir, -S(0)2NRnRir, -NRnC(0)NR Rir■, -SRn , -S(0)Rn, S(0)2Rn, -CN, haloalkyl, haloalkoxy, -C(0)ORn, -C(0)NRnRir, -OCH2CH2OR ,, NRiiS(0)2NRirRir' and C(CH3)2ORn; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a preferred embodiment of the compound according to the invention of general Formula (I) and in relation to Ri of any of the embodiments of the present invention, the alkyl, alkenyl or alkynyl in Ri, if substituted, is substituted with one or more substituent/s selected from -OR , halogen, -CN, haloalkyl, haloalkoxy and -NRnRir; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a preferred embodiment of the compound according to the invention of general Formula (I) and in relation to R2 of any of the embodiments of the present invention, the cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -N02, -NRi2Ri2', NRi2C(0)Ri2', - NR12S(0)2Ri2 , -S(0)2NRi2Ri2'. -NRi2C(0)NRi2'Ri2", -SR12, -S(0)R12, S(0)2Ri2, -
CN, haloalkyl, haloalkoxy, -C(0)ORi2, -C(0)NRi2Riz, -OCH2CH2OR12, - NRi2S(0)2NRi2 Ri2" and C(CH3)2ORi2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a preferred embodiment of the compound according to the invention of general Formula (I) and in relation to R2 of any of the embodiments of the present invention, the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from -ORi2, halogen, -CN, haloalkyl, haloalkoxy, -NR12R12'; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a preferred embodiment of the compound according to the invention of general Formula (I) and in relation to alkyls other than those defined in Ri or R2 of any of the embodiments of the present invention, the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a preferred embodiment of the compound according to the invention of general Formula (I) and in relation to alkyls other than those defined in Ri or R2 of any of the embodiments of the present invention, the alkyl, alkenyl or alkynyl, other than those defined in Ri or R2, if substituted, is substituted with one or more-ORi3; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In a preferred embodiment of the compound according to the invention of general Formula (I) and in relation to the cycloalkyl, aryl or heterocyclyl other than those defined in Ri or R2 of any of the embodiments of the present invention, the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in Ri or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -ORu, -N02, -NRi4Ri4', NRi4C(0)Ri4', - NRi4S(0)2Ri4', -S(0)2NRi4Ri4-, - NRi4C(0)NR14 Ri4-, -SRi4 , -S(0)Ri4, S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)ORi4, -C(0)NRi Ri ', -OCH2CH2ORi4, -NRi4S(0)2NRi4 Ri -
Figure imgf000123_0001
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
In an embodiment of the compound according to the invention of general Formula (I), the halogen is fluorine, chlorine, iodine or bromine; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the σι receptor and the μ-opioid receptor it is a very preferred embodiment in which the compounds are selected which act as dual ligands of the σι receptor and the μ-opioid receptor and especially compounds which have a binding expressed as K, which is preferably < 1000 nM for both receptors, more preferably < 500 nM, even more preferably < 100 nM.
In the following the phrase "compound of the invention" is used. This is to be understood as any compound according to the invention as described above according to general Formulae (I), (la), (Γ), (I2'), (I3'), (I4'), (I5 ), (l5a'), (l5 ').
The compounds of the invention represented by the above described Formula (I) may include enantiomers depending on the presence of chiral centres or isomers depending on the presence of multiple bonds (e.g. Z, E). The single isomers, enantiomers or diastereoisomers and mixtures thereof fall within the scope of the present invention.
In general the processes are described below in the experimental part. The starting materials are commercially available or can be prepared by conventional methods. A preferred aspect of the invention is also a process for the production of a compound according to Formula (I), following scheme 1.
A preferred aspect of the invention is a process for the production of a compound according to Formula (I), wherein Ri , R2, R3, R4, R4', R4-, R ", Rs, R5 , Rw, Rw\ m, n, p, q, r, X, Y and W are as defined in the description, following scheme 1.
For the sake of clarity the expression "a compound according to Formula (I), wherein e.g. Ri , etc. are as defined in the description" would (just like the expression "a compound of Formula (I) as defined in any one of claims e.g. 1 to 9" found in the claims) refer to "a compound according to Formula (I)", wherein the definitions of the respective substituents Ri etc. (also from the cited claims) are applied. In addition, this would also mean, though (especially in regards to the claims) that also one or more disclaimers defined in the description (or used in any of the cited claims like e.g. claim 1) would be applicable to define the respective compound. Thus, a disclaimer found in e.g. claim 1 would be also used to define the compound "of Formula (I) as defined in any one of the corresponding related claims e.g. 1 to 9".
A process is described in Scheme 1 for the preparation of compounds of general formula I, wherein Ri , R2, R3, R4, R4\ R4-, R4 m, n, p, q, r, W and X have the meanings defined in the description and Z is chloro or bromine.
A preferred embodiment of the invention is a process for the production of a compound according to Formula (I),
Figure imgf000125_0001
wherein compounds of general formula IV
Figure imgf000126_0001
IV are treated with a lithium salt in situ generated from compounds of general formula VII
Z-R 1
VII with nBuLi, in a suitable solvent, preferably in tetrahydrofuran, at a suitable temperature, preferably at room temperature, and subsequently hydrolized to ketone compounds of formula I in the presence of an aqueous inorganic acid such as HCI, wherein Ri , R2, R3, R4, R4', Rc, R4 ", m, n, p, q, r, W and X have the meanings defined in the description and Z is a chlorine or bromine atom.
A preferred embodiment of the invention is a process, for the production of a compound according to Formula (I) starting from a compound of Formula (IV),
1. Z-R-, , nBuLi
Figure imgf000126_0002
wherein Ri , R2, R3, R4, 4', R4", R4-, m, n, p, q, r, W and X have the meanings defined in the description and Z is chlorine or bromine. A preferred embodiment of the invention is a process, wherein n is 0 and W is -N(Rw)- ,, for the production of a compound according to Formula (IV) starting from a compound of Formula (II),
Figure imgf000127_0001
II lv , wherein R2,
R3, R4, R4\ R4", R4"\ m, p, q, r, and X have the meanings defined in the description and
Z is chlorine or bromine.
A preferred embodiment of the invention is a process, wherein n is 1 , 2 or 3, or n = 0 and W is -C(RwRw)-, for the production of a compound according to Formula (IV) starting from a compound of Formula (V),
Figure imgf000127_0002
VI
for n=1 , 2 or 3
Figure imgf000127_0003
V , wherein R2, R3, R4, R4\ R4-, R4- , m, p, q, r and X have the meanings defined in the description and Z is chlorine or bromine. In another particular embodiment a compound of Formula (II),
Figure imgf000128_0001
II
used for the preparation of a compound of Formula (I).
In another particular embodiment a compound of Formula (III),
Figure imgf000128_0002
used for the preparation of a compound of Formula (I).
In another particular embodiment a compound of Formula (IV),
Figure imgf000128_0003
used for the preparation of a compound of Formula (I). In another particular embodiment a compound of Formula (V),
Figure imgf000129_0001
V is used for the preparation of a compound of Formula (I).
In another particular embodiment a compound of Formula (VI),
Figure imgf000129_0002
VI is used for the preparation of a compound of Formula (I).
In another particular embodiment a compound of Formula (VII),
Z-R1
VII is used for the preparation of a compound of Formula (I).
In another particular embodiment there is a use of the compounds of Formula II, III, IV, V, VI or VII,
Figure imgf000130_0001
Figure imgf000130_0002
, wherein Ri , R2, R3, R4, R4\ R4", R4 ", m, n, p, q, r, W and X have the meanings defined in the description and Z is chlorine or bromine, for the preparation of compounds of Formula (I).
In another particular embodiment, these are compounds of Formula II, III, IV, V, VI or VII,
Figure imgf000130_0003
,
R4, R4', R4 ", 4 "·, m, n, p, q, r, W and X have the meanings defined in the description and Z is chlorine or bromine, for use in the preparation of compounds of Formula (I).
The obtained reaction products may, if desired, be purified by conventional methods, such as crystallisation and chromatography. Where the above described processes for the preparation of compounds of the invention give rise to mixtures of stereoisomers, these isomers may be separated by conventional techniques such as preparative chromatography. If there are chiral centres the compounds may be prepared in racemic form, or individual enantiomers may be prepared either by enantiospecific synthesis or by resolution.
One preferred pharmaceutically acceptable form of a compound of the invention is the crystalline form, including such form in pharmaceutical composition. In the case of salts and also solvates of the compounds of the invention the additional ionic and solvent moieties must also be non-toxic. The compounds of the invention may present different polymorphic forms, it is intended that the invention encompasses all such forms.
Another aspect of the invention refers to a pharmaceutical composition which comprises a compound according to the invention as described above according to general formula I or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle. The present invention thus provides pharmaceutical compositions comprising a compound of this invention, or a pharmaceutically acceptable salt or stereoisomers thereof together with a pharmaceutically acceptable carrier, adjuvant, or vehicle, for administration to a patient.
Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules etc.) or liquid (solutions, suspensions or emulsions) composition for oral, topical or parenteral administration.
In a preferred embodiment the pharmaceutical compositions are in oral form, either solid or liquid. Suitable dose forms for oral administration may be tablets, capsules, or solutions and may contain conventional excipients known in the art such as binding agents, for example syrup, acacia, gelatine, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose, sugar, maize starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulfate.
The solid oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are conventional in the art. The tablets may for example be prepared by wet or dry granulation and optionally coated according to methods well known in normal pharmaceutical practice, in particular with an enteric coating.
The pharmaceutical compositions may also be adapted for parenteral administration, such as sterile solutions, suspensions or lyophilized products in the appropriate unit dosage form. Adequate excipients can be used, such as bulking agents, buffering agents or surfactants.
The mentioned formulations will be prepared using standard methods such as those described or referred to in the Spanish and US Pharmacopoeias and similar reference texts. Administration of the compounds or compositions of the present invention may be by any suitable method, such as intravenous infusion, oral preparations, and intraperitoneal and intravenous administration. Oral administration is preferred because of the convenience for the patient and the chronic character of the diseases to be treated. Generally an effective administered amount of a compound of the invention will depend on the relative efficacy of the compound chosen, the severity of the disorder being treated and the weight of the sufferer. However, active compounds will typically be administered once or more times a day for example 1 , 2, 3 or 4 times daily, with typical total daily doses in the range of from 0.1 to 1000 mg/kg/day. The compounds and compositions of this invention may be used with other drugs to provide a combination therapy. The other drugs may form part of the same composition, or be provided as a separate composition for administration at the same time or at different time.
Another aspect of the invention refers to the use of a compound of the invention or a pharmaceutically acceptable salt or isomer thereof in the manufacture of a medicament.
Another aspect of the invention refers to a compound of the invention according as described above according to general formula I, or a pharmaceutically acceptable salt or isomer thereof, for use as a medicament for the treatment of pain. Preferably the pain is medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia. This may include mechanical allodynia or thermal hyperalgesia.
Another aspect of the invention refers to the use of a compound of the invention in the manufacture of a medicament for the treatment or prophylaxis of pain.
In a preferred embodiment the pain is selected from medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, also preferably including mechanical allodynia or thermal hyperalgesia. Another aspect of this invention relates to a method of treating or preventing pain which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound as above defined or a pharmaceutical composition thereof. Among the pain syndromes that can be treated are medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, whereas this could also include mechanical allodynia or thermal hyperalgesia.
The present invention is illustrated below with the aid of examples. These illustrations are given solely by way of example and do not limit the general spirit of the present invention.
General Experimental Part (Methods and Equipment of the synthesis and analysis
A process is described in Scheme 1 for the preparation of compounds of general formula I, wherein Ri, R2, R3, R4, R4', R4-, R4 -, m, n, p, q, r, W and X have the meanings defined above and Z is chlorine or bromine.
Figure imgf000134_0001
V
Scheme 1
This process is carried out as described below:
Step 1 : The compounds of general formula IV wherein n is 0 and W is -N(Rw)-, are prepared by Strecker reaction of ketone derivatives of formula II with amino compounds of formula III using a metal cyanide, preferably potassium cyanide, in the presence of an acid catalyst, in water at room temperature. Additionally, compounds of formula IV wherein n is 1 , 2 or 3, can be obtained by treatment of cyano derivatives of formula V with compounds of formula VI in the presence of a strong base, preferably lithium diisopropylamide, in a suitable solvent, such as tetrahydrofuran, and at a suitable temperature comprised between 0 °C and room temperature.
Step 2: Compounds of general formula IV are treated with a lithium salt in situ generated from compounds of general formula VII with nBuLi, in a suitable solvent, preferably in tetrahydrofuran, at a suitable temperature comprised between -78 °C and room temperature, preferably at room temperature. In a subsequent reaction, the obtained imine intermediate compound is hydrolized to ketone compounds of formula I in the presence of an aqueous inorganic acid such as HCI.
The process described by Steps 1 to 2 represents the general route for the preparation of compounds of formula I. Additionally, the functional groups present in any of the positions can be interconverted using reactions known to those skilled in the art.
In some of the processes described above it may be necessary to protect the reactive or labile groups present with suitable protecting groups, such as for example Boc (tert- butoxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl) or benzyl for the protection of amino groups. The procedures for the introduction and removal of these protecting groups are well known in the art and can be found thoroughly described in the literature.
In addition, a compound of formula I that shows chirality can also be obtained by resolution of a racemic compound of formula I either by chiral preparative HPLC or by crystallization of a diastereomeric salt or co-crystal. Alternatively, the resolution step can be carried out at a previous stage, using any suitable intermediate. Compounds of formula II, III, V, VI, and VII where R1 , R2, R3, R4, R4\ R4", R4'", m, n, p, q, r, W and X have the meanings defined above, are commercially available or can be prepared by conventional methods described in the bibliography.
EXAMPLES:
Intermediates and Examples
The following abbreviations are used in the examples:
ACN: Acetonitrile
AcOEt: Ethyl acetate
Aq: aqueous
CH: Cyclohexane
DCM: Dichloromethane DCE: 1 ,2-Dicloroethane
CHCI3: Chloroform
DIPEA: A/./V-Diisopropylethylamine
DMPU: 1 ,3-Dimethyltetrahydropyrimidin-2(1 H)-one
Et20: Diethyl ether Ex: Example h: Hour/s
HPLC: High-performance liquid chromatography INT: Intermediate LDA: Lithium diisopropilamide MeOH: Methanol MS: Mass spectrometry Min: Minutes
NaBH4: Sodium borohydride Ret: Retention rt: Room temperature Sat: Saturated THF: Tetrahydrofuran
The following methods were used to obtain the HPLC-MS data:
A: Column Acquity UPLC BEH C18 2.1x50 mm, 1.7 μηι; flow rate 0.61 mL/min; A: NH4HC03 10mM; B: ACN; Gradient: 0.3 min in 98% A, 98% A to 0% A in 2.7 min, 2 min in 0% A, 0% A to 98% A in 0.2 min, 0.55 min in 98% A
B: Column: Aqcuity BEH C18 2.1x50 mm 1.7μηη; flow rate 800 μΙ/min; A: NH HC03 10mM; B: ACN; Gradient: 0.3 min in 90% A, 90% A to 5% A in 2.7 min, 0.7 min in 5% A, 5% A to 90% A in 0.1 min, 1.2 min in 90% A Intermediate 1A. 4-((2-(Benzyl(isopentyl)amino)ethyl)(methyl)amino)-2,2- dimethyltetrahydro-2H-pyran-4-carbonitrile.
Figure imgf000138_0001
In a 50 mL round bottomed flask, 2,2-dimethyldihydro-2/-/-pyran-4(3/7)-one (0.3 g, 2.3 mmol) was dissolved in water (15 mL) along with sodium metabisulfite (0.22 g, 1.17 mmol). The mixture was allowed to stir at rt for 1 h and A^-benzyl-A^-isopentyl-A/2- methylethane-1 ,2-diamine dihydrochloride (0.72 g, 2.3 mmol) and DIPEA (1.6 mL, 9.4 mmol) were added. The mixture was stirred for 2 h and potassium cyanide (0.243 g, 3.7 mmol) was added to the reaction mixture. The reaction was stirred at rt until full conversion was achieved (12 days). The colourless solution was extracted with ethyl acetate and the combined organic phases were washed with NaHCC>3, dried over MgSC>4, filtered and concentrated to dryness to give the title compound as yellow oil (0.65 g, yield 75%).
Ή-NMR (400 MHz, CDC13) δ ppm: 7.41 - 7.13 (m, 5H), 3.83 - 3.77 (m, 2H), 3.58 (s, 2H), 2.61 - 2.41 (m, 4H), 2.23 (s, 3H), 2.02 - 1.93 (m, 2H), 1.69 - 1.51 (m, 5H), 1.49 - 1.39 (m, 2H), 1.38 (s, 3H), 1.23 (s, 3H), 0.86 (d, J = 6.6 Hz, 6H)
Intermediate 1 B. 4-(3-(Benzyl(2-isopropoxyethyl)amino)propyl)-2,2- dimethyltetrahydro-2H-pyran-4-carbonitrile.
Figure imgf000139_0001
To a solution of 2,2-dimethyltetrahydro-2/-/-pyran-4-carbonitrile (168 mg, 1.2 mmol) in dry THF (3 mL) cooled at 0 °C, a solution of lithium diisopropylamide (1.5 M in THF, 1.13 mL, 1.7 mmol) was added dropwise under nitrogen atmosphere. The mixture was stirred at rt for 40 min. Then it was cooled down again to 0 °C, and a solution of N- benzyl-3-iodo-A/-(2-isopropoxyethyl)propan-1 -amine (436 mg, 1.2 mmol) and DMPU (0.65 mL, 5.4 mmol) in dry THF (3 mL) were added. The reaction mixture was allowed to reach rt and stirred for 3 h. The solvent was evaporated and the residue was diluted with water and Et20. The phases were separated and the aqueous phase was extracted with Et20. The organic phases were combined and washed with aq NaHCC sat solution. The solvent was evaporated and the residue thus obtained was purified by flash chromatography on silica gel, gradient DCM to DCM:MeOH (90: 10) to give the title compound (420 mg, 94% yield).
HPLC-MS (Method B): Ret, 2.56 min; ESI+-MS m/z, 373.2 (M+H).
This method was used for the preparation of intermediate 1 C using the suitable alkyl halide:
Figure imgf000139_0002
4-(3-
(benzyl(isopentyl)
amino)propyl)-2,2-
1 C B 3.33 357.4
dimethyltetrahydro
-2H-pyran-4- carbonitrile
Example 1. (4-((2-(Benzyl(isopentyl)amino)ethyl)(methyl)amino)-2,2- dimethyltetrahydro-2H-pyran-4-yl)(pyridin-2-yl)methanone.
Figure imgf000140_0001
a) /V1-Benzyl-A/2-(4-(imino(pyridin-2-yl)methyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)- A/^isopentyl-A^-methylethane-l ^-diamine
2-Bromopyridine (0.36 mL, 3.8 mmol) in THF, under argon atmosphere, was cooled down to -78 °C and n-BuLi (1.6 M in hexane, 2.5 mL, 4 mmol) was added. The reaction was kept for 30 min at this temperature and a solution of 4-((2- (benzyl(isopentyl)amino)ethyl)(methyl)amino)-2,2-dimethyltetrahydro-2/-/-pyran-4- carbonitrile (INT 1A, 426 mg, 1.15 mmol.) in THF (12 mL) was added. The reaction was slowly allowed to reach rt and stirred overnight. The mixture was quenched with NH4CI and extracted with Et.20. The combined organic fractions were dried over Na2SC>4 and the solvent was removed under reduced pressure, to give the crude title compound as an oil that was used in the following step without further purification.
HPLC-MS (Method A): Ret, 2.77 min; ESI+-MS m/z, 451.3 (M+1 ). b) Title compound.
The crude imine obtained in step a (0.52 g, 1.15 mmol) was dissolved in THF (17 mL) and 3 N HCI (ca. 5.5 mL) was added. The reaction was stirred until full conversion to ketone was achieved (HPLC analysis). The mixture was made alkaline with 10% NaOH and extracted twice with Et.20. The combined organic phases were dried over NaaSO-t, filtered and concentrated to give a brown oil. The crude product was purified by flash chromatography on silica gel, eluents CH:AcOEt, gradient to 80:20 to give the title compound (118 mg, yield 23% over two steps).
HPLC-MS (Method A): Ret, 3.03 min; ESI+-MS m/z, 452.3 (M+1).
This method was used for the preparation of Examples 2 and 3 using intermediates 1 B and 1 C as starting materials:
Figure imgf000141_0001
(4-(3-(benzyl(2- isopropoxyethyl)a
mino)propyl)-2,2-
3 dimethyltetrahydro A 3.28 453.4
-2H-pyran-4-
Figure imgf000142_0001
yl)(pyridin-2- yl)methanone
Example 4. (4-((2-(lsopentylamino)ethyl)(methyl)amino)-2,2-dimethyltetrahyd pyran-4-yl)(pyridin-2-yl)methanone
Figure imgf000142_0002
To a solution of (4-((2-(benzyl(isopentyl)amino)ethyl)(methyl)amino)-2,2- dimethyltetrahydro-2H-pyran-4-yl)(pyridin-2-yl)methanone (Ex 1 , 30 mg, 0.07 mmol,) in DCE (1 mL), dichloroethyl formate (15 μί, 0.13 mmol) was added and the reaction mixture heated to reflux for 2 h. After cooling down to rt, all volatiles were removed under reduced pressure. MeOH (1 mL) was then added and the reaction mixture heated again to reflux for 2 h. After cooling back to rt, the solvent was removed and the brown solid thus obtained was washed several times with Et20 and dried in vacuum to give the title compound as oil (45 mg, yield 70%).
HPLC-MS (Method A): Ret, 1.93 min; ESI+-MS m/z, 362.3 (M+1 ). This method was used for the preparation of Ex 5 and 6 using Ex 2 and 3, respectively, as starting materials.
Figure imgf000143_0002
Example 7. (4-((2-(lsopentyl(methyl)amino)ethyl)(methyl)amino)-2,2- dimethyltetrahydro-2H-pyran-4-yl)(pyridin-2-yl)methanone.
Figure imgf000143_0001
(4-((2-(lsopentylamino)ethyl)(methyl)ami
yl)(pyridin-2-yl)methanone (Ex 4, 35 mg, 0.097 mmol) was dissolved in formic acid (0.36 ml_, 9.7 mmol) and formaldehyde (37% aqueous solution, 0.72 mL, 9.7 mmol) and the reaction mixture was stirred at 90 °C overnight. The mixture was then diluted with AcOEt and washed with aq NaHC03 sat solution. The organic layer was dried over Na2SC>4, filtered and concentrated. The crude residue was purified by flash chromatography on silica gel (eluents DCM:MeOH from 5% to 30% B) to give the title compound as an oil (10 mg, yield 28%).
HPLC-MS (Method A): Ret, 1.90 min; ESI+-MS m/z, 376.3 (M+1).
This method was used for the preparation of Ex 8 and 9 using Ex 5 and 6, respectively, as starting materials:
Figure imgf000144_0001
yl)(pyridin-2- yl)methanone.
BIOLOGICAL ACTIVITY
Pharmacological study
Human σι receptor radioligand assay
To investigate binding properties of test compounds to human σι receptor, transfected HEK-293 membranes and [3H](+)-pentazocine (Perkin Elmer, NET-1056), as the radioligand, were used. The assay was carried out with 7 pg of membrane suspension, 5 nM of [3H](+)-pentazocine in either absence or presence of either buffer or 10 μΜ Haloperidol for total and non-specific binding, respectively. Binding buffer contained Tris-HCI 50 mM at pH 8. Plates were incubated at 37 °C for 120 minutes. After the incubation period, the reaction mix was then transferred to Multiscreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris-HCL (pH7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail. Preferably, transfected HEK-293 membranes (7 μg) were incubated with 5 nM of [3H](+)-pentazocine in assay buffer containing Tris-HCI 50 mM at pH 8. NBS (nonspecific binding) was measured by adding 10 μΜ Haloperidol. The binding of the test compound was measured at five different concentrations. Plates were incubated at 37 °C for 120 minutes. After the incubation period, the reaction mix was then transferred to MultiScreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris-HCL (pH7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail. Human u-opioid receptor radioligand assay
To investigate binding properties of test compounds to human μ-opioid receptor, transfected CHO-K1 cell membranes and [3H]-DAMGO (Perkin Elmer, ES-542-C), as the radioligand, were used. The assay was carried out with 20 pg of membrane suspension, 1 nM of [3H]-DAMGO in either absence or presence of either buffer or 10 μΜ Naloxone for total and non-specific binding, respectively. Binding buffer contained Tris-HCI 50 mM, MgCI2 5 mM at pH 7.4. Plates were incubated at 27°C for 60 minutes. After the incubation period, the reaction mix was then transferred to Multiscreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris- HCL (pH 7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail. Preferably, transfected CHO-K1 cell membranes (20 pg) were incubated with 1 nM of [3H]-DAMGO in assay buffer containing Tris-HCI 50 mM, MgCI2 5 mM at pH 7.4. NBS (non-specific binding) was measured by adding 10 μΜ Naloxone. The binding of the test compound was measured at five different concentrations. Plates were incubated at 27°C for 60 minutes. After the incubation period, the reaction mix was then transferred to Multiscreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris-HCL (pH 7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail.
Results:
As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the σι receptor and the μ-opioid receptor it is a very preferred embodiment in which the compounds are selected which act as dual ligands of the σι receptor and the μ-opioid receptor and especially compounds which have a binding expressed as K, which is preferably < 1000 nM for both receptors, more preferably < 500 nM, even more preferably < 100 nM.
The following scale has been adopted for representing the binding to the σι receptor and the μ-opioid receptor expressed as K,:
+ Both Ki-μ and Κι-σι >= 1000 nM ++ One Ki <1000 nM while the other Ki is >=1000 nM
+++ Both Ki-μ and Κ,-σι < 1000 nM
++++ Both Ki-μ and Κι-σι < 500 nM
All compounds prepared in the present application exhibit binding to the σι receptor and the μ-opioid receptor, in particular the following binding results are shown:
Figure imgf000147_0001

Claims

CLAIMS:
1. Compound of general Formula (I):
Figure imgf000148_0001
(I) wherein m is 0, 1 or 2; r is 0, 1 or 2; n is 0, 1 , 2 or 3; p is 1 , 2 or 3; q is 1 , 2 or 3;
X is a bond or -O-; Y is selected from -O- and -S-;
W is -C(RwRw)- or -N(RW)-; wherein Rw is selected from hydrogen, substituted or unsubstituted Ci-e alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C^e alkynyl, Rw' is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
Ri is selected from substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-e alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyi, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;
R4 and R4' are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R4 and R4' may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; R4" and R4- are independently selected from hydrogen, substituted or unsubstituted Ci- 6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R - and R4- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
2. Compound according to claim 1 wherein the compound of Formula (I) is a compound of Formula (Γ), (la), (I2'), (I3'), (I4'), (I5'), (l5a'), (l5t"),
Figure imgf000150_0001
(I"). a compound of Formula (la)
Figure imgf000150_0002
a compound of Formula (I2')
Figure imgf000151_0001
a compound of Formula (I4')
Figure imgf000152_0001
Figure imgf000152_0002
151
Figure imgf000153_0001
compound of Formula (l5 ')
Figure imgf000153_0002
wherein R5 and R5' are independently selected from halogen, -Rn, -ORn, -NO2, -NR11R11', -NRnC(0)Rir, -NRnS(0)2Rir, -S(0)2NRnRir, -NR C(0)NRn Rir,
-SR11 , -S(0)Rii, -S(0)2Rii, -CN, haloalkyl, haloalkoxy, -C(0)ORn, - C(0)NRiiRir, -OCH2CH2ORn, -NRnS(0)2NRirRii" and -C(CH3)2ORn; and R11 , Ru and Rn- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2.e alkenyl and unsubstituted C2-6 alkynyl.
3. Compound according to any one of claims 1 or 2 wherein R2 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; preferably selected from substituted or unsubstituted Ci-6 alkyl and substituted or unsubstituted aryl; more preferably selected from substituted or unsubstituted isopropyl, substituted or unsubstituted isobutyl and substituted or unsubstituted phenyl.
4. Compound according to any one of claims 1 to 3 wherein R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyi, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; preferably R3 is selected from hydrogen, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted isopentyl and substituted or unsubstituted benzyl.
5. Compound according to any one of claims 1 to 4 wherein n is 0 or 1.
6. Compound according to any one of claims 1 to 5 wherein p is 1 or 2.
7. Compound according to any one claims 1 to 6 wherein q is 1 or 2.
8. Compound according to any one claims 1 to 7 wherein m is 1 and r is 1
Compound according to any one of claims 1 to 8 wherein the compound selected from
Figure imgf000154_0001
3 (4-(3-(benzyl(2-isopropoxyethyl)amino)propyl)-2,2-dimethyltetrahydro-2/-/-pyran- 4-vD(Pvridin-2-vl)methanone
4 (4-((2-(lsopentylamino)ethyl)(methyl)ami
vl)(Pvridin-2-vl)methanone
5 (4-(3-(isopentylamino)propyl)-2,2-dimethyltetrahydro-2/-/-pyran-4-yl)(pyridin-2- vDmethanone
6 (4-(3-((2-isopropoxyethyl)amino)propyl)-2,2-dimethyltetrahydro-2/-/-pyran-4- vl)(Dvridin-2-vl)methanone
7 (4-((2-(isopentyl(methyl)amino)ethyl)(methyl)amino)-2,2-dimethyltetrahy
pvran-4-vl)(pvridin-2-vl)methanone
8 (4-(3-(isopentyl(methyl)amino)propyl)-2,2-dimethyltetrahydro-2/-/-pyran-4- vl)(Pvridin-2-vl)methanone
9 (4-(3-((2-isopropoxyethyl)(methyl)amino)propyl)-2,2-dimethyltetrahydro-2H-pyran- 4-vl)(Pvridin-2-vl)methanone
10. Process for the preparation of compounds of Formula (I) as defined in any one of claims 1 to 9, wherein compounds of general formula IV
Figure imgf000155_0001
IV are treated with a lithium salt in situ generated from compounds of general formula VII
Z-R 1
VII with nBuLi, in a suitable solvent, preferably in tetrahydrofuran, at a suitable temperature, preferably at room temperature, and subsequently hydrolized to ketone compounds of formula I in the presence of an aqueous inorganic acid such as HCI, wherein Ri, R2, R3, R , R4', R4", R4-, m, n, p, q, r, W and X have the meanings defined in the preceeding claims and Z is chlorine or bromine. Use of the compounds of Formula II, III, IV, V, VI or VII,
Figure imgf000156_0001
Figure imgf000156_0002
, wherein Ri ,
R2, R3, R4, R4', R4 ", R4 ", m, n, p, q, r, W and X have the meanings defined in the description and Z is chlorine or bromine, for the preparation of compounds of Formula (I) as defined in any one of claims 1 to 9.
12. A pharmaceutical composition which comprises a compound of Formula (I) as defined in any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.
13. A compound of Formula (I) as defined in any one of claims 1 to 9 for use as a medicament.
14. A compound of Formula (I) as defined in any one of claims 1 to 9 for use as a medicament; preferably for use as a medicament for the treatment of pain, especially medium to severe pain, visceral pain, chronic pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia.
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