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WO2000073299A1 - Composes sulfonamide a activite pharmaceutique - Google Patents

Composes sulfonamide a activite pharmaceutique Download PDF

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Publication number
WO2000073299A1
WO2000073299A1 PCT/EP2000/004893 EP0004893W WO0073299A1 WO 2000073299 A1 WO2000073299 A1 WO 2000073299A1 EP 0004893 W EP0004893 W EP 0004893W WO 0073299 A1 WO0073299 A1 WO 0073299A1
Authority
WO
WIPO (PCT)
Prior art keywords
toluene
sulfonyl
piperidin
ylmethyl
pyrrolidin
Prior art date
Application number
PCT/EP2000/004893
Other languages
English (en)
Inventor
Peter John Lovell
Original Assignee
Smithkline Beecham P.L.C.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Smithkline Beecham P.L.C. filed Critical Smithkline Beecham P.L.C.
Priority to AU50734/00A priority Critical patent/AU5073400A/en
Priority to JP2000621365A priority patent/JP2003500488A/ja
Priority to EP00935141A priority patent/EP1181287A1/fr
Publication of WO2000073299A1 publication Critical patent/WO2000073299A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/24—Antidepressants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/48—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention relates to compounds having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS and other disorders.
  • WO 97/29097, WO 97/48681 and WO 97/49695 all disclose a series of sulphonamide derivatives that are 5-HT ⁇ receptor antagonists and are said to be useful in the treatment of various CNS diseases.
  • a structurally novel class of compounds have now been found that also possess 5-HT7 receptor activity.
  • the present invention therefore provides, in a first aspect, a compound of formula (I) or a pharmaceutically acceptable salt thereof:
  • R.1, R2 and R ⁇ are independently hydrogen, halogen, hydroxy, C galkyl or C ⁇ . galkoxy; m is 1 or 2,
  • X is nitrogen, carbon or CH, is a single bond when X is nitrogen or a CH; or is a double bond when X is carbon;
  • P is phenyl, naphthyl, a 5 or 6 membered heteroaryl ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur, or a benzofused heteroaryl ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur;
  • R 4 is C ⁇ _6alkyl optionally substituted by NR 5 R 6 , aryl, arylC ⁇ .g alkyl, Cj.galkoxy, C ⁇ 6alkylthio, cyano, hydroxy, nitro, halogen, CF3, C2F5, NR 5 R 6 , CONR 5 R 6 ,
  • Ci .galkyl groups whether alone or as part of another group may be straight chain or branched.
  • the term 'halogen' is used herein to describe, unless otherwise stated, a group selected from fluorine, chlorine, bromine or iodine.
  • the term 'aryl' is used herein to describe, unless otherwise stated, a group such as phenyl or naphthyl. Such aryl groups may be optionally substituted by one or more C ⁇ _ galkyl or halogen.
  • the groups R , R ⁇ and R ⁇ are independently hydrogen, halogen such as fluorine, chlorine or bromine or C ⁇ _ galkyl such as methyl.
  • D is a single bond.
  • P is naphthyl this is intended to denote both naphthalen-1-yl and naphthalen-2-yl groups.
  • P is a 5 or 6 membered heteroaryl ring
  • suitable examples include thienyl, furyl, pyrrolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimidyl, pyrrolidinyl and pyrazinyl.
  • P is a benzofused heteroaryl ring suitable examples include indolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinolinyl and isoquinolinyl.
  • P is phenyl, naphthyl, benzimidazol-2-yl, 2-oxo-2,3 -dihydrobenzimidazol-1-yl, indol-3-yl, benzoxazol-2-yl and benzothiazol-2- yi-
  • R 4 groups include halogen such as fluorine or chlorine, Ci .galkyl optionally substituted by NR ⁇ R6 such as methyl, hydroxy, CF3, C ⁇ _ galkoxy such as methoxy or groups COR 7 or CO2R 7 in which R 7 is methyl.
  • n 2 or more the groups R 4 can be the same or different.
  • n is 0 or 1.
  • Particularly preferred compounds of the invention include: (R)-2-( 1 -( 1 -(Toluene-3-sulfony l)-pyrrolidin-2-ylmethyl)-piperidin-4-yl)- 1 H- benzimidazole, (S)-2-( 1 -( 1 -(Toluene-3 -sulfonyl)-pyrrolidin-2-ylmethyl)-piperidin-4-y 1)- 1 H- benzimidazole,
  • the compounds of the formula (I) can form acid addition salts with acids, such as conventional pharmaceutically acceptable acids, for example maleic, hydrochloric, hydrobromic, phosphoric, acetic, fumaric, salicylic, citric, lactic, mandelic, tartaric and methanesulphonic.
  • acids such as conventional pharmaceutically acceptable acids, for example maleic, hydrochloric, hydrobromic, phosphoric, acetic, fumaric, salicylic, citric, lactic, mandelic, tartaric and methanesulphonic.
  • Certain compounds of formula (I) are capable of existing in stereoisomeric forms including diastereomers and enantiomers and the invention extends to each of these stereoisomeric forms and to mixtures thereof including racemates.
  • the different stereoisomeric forms may be separated one from the other by the usual methods, or any given isomer may be obtained by stereospecific or asymmetric synthesis.
  • the invention also extends to any tautomeric forms and mixtures thereof.
  • the present invention also provides, in a further aspect, a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, which process comprises coupling a compound of formula (II):
  • Suitable leaving groups Y include halogen (particularly chloro) and OSO2Nr groups such as tosylate.
  • the reaction of a compounds of formulae (II) and (III) is preferably carried out in a solvent such as dichloromethane or acetonitrile optionally in the presence of sodium iodide and a base such as potassium carbonate.
  • Compounds of formula (I) and their pharmaceutically acceptable salts have 5-HT7 receptor antagonist activity and are believed to be of potential use for the treatment or prophylaxis of certain CNS disorders such as anxiety, depression, sleep disorders (including disturbances of Circadian rhythms), migraine, Parkinson's disease, schizophrenia, pain, appetite disorders and other indications such as inflammation, spastic colon, renal disorders, hypotension, cardiovascular shock, disorders associated with neuronal degeneration resulting from ischaemic events such as stroke, septic shock and gastrointestinal diseases such as IBS (irritable bowel syndrome).
  • CNS disorders such as anxiety, depression, sleep disorders (including disturbances of Circadian rhythms), migraine, Parkinson's disease, schizophrenia, pain, appetite disorders and other indications such as inflammation, spastic colon, renal disorders, hypotension, cardiovascular shock, disorders associated with neuronal degeneration resulting from ischaemic events such as stroke, septic shock and gastrointestinal diseases such as IBS (irritable bowel syndrome).
  • IBS irritable bowel syndrome
  • the invention also provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use as a therapeutic substance, in particular in the treatment or prophylaxis of the above disorders, particularly depression and/or sleep disorders.
  • the invention further provides a method of treatment or prophylaxis of the above disorders, in mammals including humans, which comprises administering to the sufferer a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof or a solvate thereof for use in the treatment or prophylaxis of depression and/or sleep disorders.
  • the present invention also provides a pharmaceutical composition, which comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient.
  • a pharmaceutical composition of the invention which may be prepared by admixture, suitably at ambient temperature and atmospheric pressure, is usually adapted for oral, parenteral or rectal administration and, as such, may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusable solutions or suspensions or suppositories. Orally administrable compositions are generally preferred.
  • Tablets and capsules for oral administration may be in unit dose form, and may contain conventional excipients, such as binding agents, fillers, tabletting lubricants, disintegrants and acceptable wetting agents.
  • the tablets may be coated according to methods well known in normal pharmaceutical practice.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspension, solutions, emulsions, syrups or elixirs, or may be in the form of a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), preservatives, and, if desired, conventional flavourings or colourants.
  • fluid unit dosage forms are prepared utilising a compound of the invention or pharmaceutically acceptable salt thereof and a sterile vehicle.
  • the compound depending on the vehicle and concentration used, can be either suspended or dissolved in the vehicle.
  • the compound can be dissolved for injection and filter sterilised before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, preservatives and buffering agents are dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner, except that the compound is suspended in the vehicle instead of being dissolved, and sterilization cannot be accomplished by filtration.
  • the compound can be sterilised by exposure to ethylene oxide before suspension in a sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
  • composition may contain from 0.1% to 99% by weight, preferably from 10 to 60% by weight, of the active material, depending on the method of administration.
  • suitable unit doses may be 0.05 to 1000 mg, more suitably 0.05 to 20.0 mg, for example 0.2 to 5 mg; and such unit doses may be administered more than once a day, for example two or three a day, so that the total daily dosage is in the range of about 0.5 to 100 mg; and such therapy may extend for a number of weeks or months.
  • the title compound can be prepared according to procedures described in J. Med.
  • the title compound can be prepared according to procedures described in J. Med. Chem., 1992, 35(26), 4813.
  • Examples El 3 - El 8 shown in Table 2 were prepared using the procedure described in Example 1 using D3 and a 4-substituted piperidine or piperazine. Such reagents are either commercially available or can be prepared by methods described above.
  • the affinity of the compounds of this invention for the 5-HT7 receptor binding site can be determined by methods described in WO 97/29097.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Anesthesiology (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

L'invention concerne de nouveaux composés sulfonamide présentant une activité antagoniste du récepteur 5-HT7, ainsi que des procédés de préparation associés, des compositions contenant ces composés et leur utilisation dans le traitement de troubles du système nerveux central et d'autres troubles.
PCT/EP2000/004893 1999-06-01 2000-05-25 Composes sulfonamide a activite pharmaceutique WO2000073299A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU50734/00A AU5073400A (en) 1999-06-01 2000-05-25 Sulfonamide compounds with pharmaceutical activity
JP2000621365A JP2003500488A (ja) 1999-06-01 2000-05-25 薬理活性を有するスルホンアミド化合物
EP00935141A EP1181287A1 (fr) 1999-06-01 2000-05-25 Composes sulfonamide a activite pharmaceutique

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9912701.1 1999-06-01
GBGB9912701.1A GB9912701D0 (en) 1999-06-01 1999-06-01 Novel compounds

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09979472 A-371-Of-International 2001-11-14
US10/305,450 Continuation US20030130275A1 (en) 1999-06-01 2002-11-27 Sulfonamide compounds with pharmaceutical activity

Publications (1)

Publication Number Publication Date
WO2000073299A1 true WO2000073299A1 (fr) 2000-12-07

Family

ID=10854529

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/004893 WO2000073299A1 (fr) 1999-06-01 2000-05-25 Composes sulfonamide a activite pharmaceutique

Country Status (5)

Country Link
EP (1) EP1181287A1 (fr)
JP (1) JP2003500488A (fr)
AU (1) AU5073400A (fr)
GB (1) GB9912701D0 (fr)
WO (1) WO2000073299A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002062788A1 (fr) * 2001-02-02 2002-08-15 Smithkline Beecham P.L.C. Composes de sulfonamide, preparation et utilisation
WO2004014428A1 (fr) * 2002-08-09 2004-02-19 Ajinomoto Co.,Inc. Remede contre les maladies intestinales et les douleurs viscerales
WO2004069828A1 (fr) * 2003-02-04 2004-08-19 Mitsubishi Pharma Corporation Compose a base de piperidine et ses applications medicinales
US7101892B2 (en) 2003-05-15 2006-09-05 Merck Sharp & Dohme Ltd. Sulfone derivatives as 5-HT7 receptor ligands
WO2008013556A1 (fr) 2006-07-27 2008-01-31 Janssen Pharmaceutical N.V. Multithérapie avec antagoniste du récepteur 5-ht7 et inhibiteur du recaptage de la sérotonine
US8188117B2 (en) 2005-07-26 2012-05-29 Sanofi-Aventis Piperidinyl-substituted isoquinolone derivatives
US8278294B2 (en) 2006-12-27 2012-10-02 Sanofi Substituted isoquinoline and isoquinolinone derivatives as inhibitors of Rho-kinase
US8399482B2 (en) 2008-06-24 2013-03-19 Sanofi 6-substituted isoquinolines and isoquinolinones
US8501736B2 (en) 2005-06-28 2013-08-06 Sanofi Isoquinoline derivatives
US8524737B2 (en) 2008-06-24 2013-09-03 Sanofi Bi- and polycyclic substituted isoquinoline and isoquinolinone derivatives
US8541449B2 (en) 2008-06-24 2013-09-24 Sanofi Substituted isoquinolines and isoquinolinones as Rho kinase inhibitors
US8618288B2 (en) 2003-09-17 2013-12-31 Janssen Pharmaceutica Nv Pyrimidine compounds as serotonin receptor modulators
US8710228B2 (en) 2006-12-27 2014-04-29 Sanofi Cycloalkylamine substituted isoquinoline derivatives
US8710077B2 (en) 2006-12-27 2014-04-29 Sanofi Cycloalkylamine substituted isoquinoline and isoquinolinone derivatives
US8742116B2 (en) 2006-12-27 2014-06-03 Sanofi Cycloalkylamine substituted isoquinolone derivatives
US8748614B2 (en) 2006-12-27 2014-06-10 Sanofi Substituted isoquinoline and isoquinolinone derivatives
US8772492B2 (en) 2006-12-27 2014-07-08 Sanofi Substituted isoquinoline and isoquinolinone derivatives

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5641436B2 (ja) * 2011-03-28 2014-12-17 国立大学法人 鹿児島大学 抗ｈｉｖ薬
JP7429652B2 (ja) * 2018-05-11 2024-02-08 テンプル・ユニバーシティ－オブ・ザ・コモンウェルス・システム・オブ・ハイアー・エデュケイション ５－ヒドロキシトリプタミン受容体７の調節物質としての新規官能化ラクタムおよびその使用方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997048681A1 (fr) * 1996-06-20 1997-12-24 Smithkline Beecham Plc Derives du sulfonamide et leur utilisation dans le traitement des troubles du systeme nerveux central
WO1999009984A1 (fr) * 1997-08-28 1999-03-04 Merck & Co., Inc. Modulateurs de pyrrolidine et de piperidine de l'activite du recepteur de chemokine

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000504677A (ja) * 1996-02-09 2000-04-18 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー ５ｈｔ７レセプター・アンタゴニスト用のスルホンアミド誘導体
WO1997049695A1 (fr) * 1996-06-25 1997-12-31 Smithkline Beecham P.L.C. Derives de sulfonamide utilises comme antagonistes du recepteur 5ht7

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997048681A1 (fr) * 1996-06-20 1997-12-24 Smithkline Beecham Plc Derives du sulfonamide et leur utilisation dans le traitement des troubles du systeme nerveux central
WO1999009984A1 (fr) * 1997-08-28 1999-03-04 Merck & Co., Inc. Modulateurs de pyrrolidine et de piperidine de l'activite du recepteur de chemokine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1181287A1 *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002062788A1 (fr) * 2001-02-02 2002-08-15 Smithkline Beecham P.L.C. Composes de sulfonamide, preparation et utilisation
WO2004014428A1 (fr) * 2002-08-09 2004-02-19 Ajinomoto Co.,Inc. Remede contre les maladies intestinales et les douleurs viscerales
WO2004069828A1 (fr) * 2003-02-04 2004-08-19 Mitsubishi Pharma Corporation Compose a base de piperidine et ses applications medicinales
US7101892B2 (en) 2003-05-15 2006-09-05 Merck Sharp & Dohme Ltd. Sulfone derivatives as 5-HT7 receptor ligands
US8618288B2 (en) 2003-09-17 2013-12-31 Janssen Pharmaceutica Nv Pyrimidine compounds as serotonin receptor modulators
US8501736B2 (en) 2005-06-28 2013-08-06 Sanofi Isoquinoline derivatives
US8722671B2 (en) 2005-06-28 2014-05-13 Sanofi Isoquinoline derivatives
US8188117B2 (en) 2005-07-26 2012-05-29 Sanofi-Aventis Piperidinyl-substituted isoquinolone derivatives
US7598255B2 (en) 2005-08-04 2009-10-06 Janssen Pharmaceutica Nv Pyrimidine compounds as serotonin receptor modulators
US8883808B2 (en) 2005-08-04 2014-11-11 Janssen Pharmaceutica N.V. Combination of 5-HT7 receptor antagonist and serotonin reuptake inhibitor therapy
WO2008013556A1 (fr) 2006-07-27 2008-01-31 Janssen Pharmaceutical N.V. Multithérapie avec antagoniste du récepteur 5-ht7 et inhibiteur du recaptage de la sérotonine
US8461144B2 (en) 2006-12-27 2013-06-11 Sanofi Substituted isoquinoline and isoquinolinone derivatives
US8278294B2 (en) 2006-12-27 2012-10-02 Sanofi Substituted isoquinoline and isoquinolinone derivatives as inhibitors of Rho-kinase
US8710228B2 (en) 2006-12-27 2014-04-29 Sanofi Cycloalkylamine substituted isoquinoline derivatives
US8710077B2 (en) 2006-12-27 2014-04-29 Sanofi Cycloalkylamine substituted isoquinoline and isoquinolinone derivatives
US8742116B2 (en) 2006-12-27 2014-06-03 Sanofi Cycloalkylamine substituted isoquinolone derivatives
US8748614B2 (en) 2006-12-27 2014-06-10 Sanofi Substituted isoquinoline and isoquinolinone derivatives
US8772492B2 (en) 2006-12-27 2014-07-08 Sanofi Substituted isoquinoline and isoquinolinone derivatives
US8399482B2 (en) 2008-06-24 2013-03-19 Sanofi 6-substituted isoquinolines and isoquinolinones
US8524737B2 (en) 2008-06-24 2013-09-03 Sanofi Bi- and polycyclic substituted isoquinoline and isoquinolinone derivatives
US8541449B2 (en) 2008-06-24 2013-09-24 Sanofi Substituted isoquinolines and isoquinolinones as Rho kinase inhibitors

Also Published As

Publication number Publication date
JP2003500488A (ja) 2003-01-07
AU5073400A (en) 2000-12-18
GB9912701D0 (en) 1999-08-04
EP1181287A1 (fr) 2002-02-27

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