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WO1999046260A1 - Nouveaux composes - Google Patents

Nouveaux composes Download PDF

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Publication number
WO1999046260A1
WO1999046260A1 PCT/SE1999/000276 SE9900276W WO9946260A1 WO 1999046260 A1 WO1999046260 A1 WO 1999046260A1 SE 9900276 W SE9900276 W SE 9900276W WO 9946260 A1 WO9946260 A1 WO 9946260A1
Authority
WO
WIPO (PCT)
Prior art keywords
indol
acid salt
amino
quinoxalin
trifluoroacetic acid
Prior art date
Application number
PCT/SE1999/000276
Other languages
English (en)
Inventor
Kostas Karabelas
Hans LÖNN
Peter Sjö
Original Assignee
Astrazeneca Ab
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 Astrazeneca Ab filed Critical Astrazeneca Ab
Priority to AU28638/99A priority Critical patent/AU2863899A/en
Publication of WO1999046260A1 publication Critical patent/WO1999046260A1/fr

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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
    • C07D401/14—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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems

Definitions

  • the present invention relates to novel quinoxalinones which are inhibitors of protein lcinase C.
  • the invention further relates to formulations comprising said inhibitors of protein kinase C, use thereof in medical therapy and in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
  • PLC Protein kinase C
  • PKC inhibitors e.g. isoquinoline sulphonamides, sphingosine and related sphingolipids, indolocarbazoles and bisindolyl- maleimides.
  • the present invention provides novel quinoxalinones which are PKC inhibitors.
  • the present invention further provides novel quinoxalinones for use in medical therapy, and more particularly in the treatment of inflammatory, immunological, broncho- pulmonary, cardiovascular, oncological or CNS-degenerative disorders.
  • the present invention also provides use of the compounds of the present invention in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
  • compositions comprising a compound according to the present invention, as active ingredient, together with a pharmaceutically acceptable adjuvant, diluent or carrier.
  • the present invention provides optionally substituted and/or annulated compounds of formula (I):
  • Rl is H, 2-amino-l -methyl-ethyl, 2-methylamino-ethyl, 2-amino-4-methyl-pentyl, piperidin-3-ylmethyl, piperidin-4-yl, 3-aminopropyl, 2-(2-amino-ethoxy)-ethyl or 5-amino- pentyl
  • R2 is H, halogen, or carboxyC 1-6 alkyl
  • R3 is C ⁇ -6 alkyl, N,N-diethylacetamid-2-yl, 4-cyanobenzyl, tetrahydro-furan-2-ylmethyl, 3-amino-propyl or 3-amino-butyl
  • R4 and R5 are each independently H, halogen, benzyloxy or carboxyQ. 6 alkyl
  • Preferred compounds are optionally substituted and/or annulated compounds comprising i) 3-[l-(3-Amino-propyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one or ii) 3-[ 1 -(4-Amino-butyl)- 1 H-indol-3-yl]-7 -phenyl- 1 H-quinoxalin-2-one
  • the present invention provides the compounds described in the Examples 1 to 155 hereto and salts thereof.
  • the most preferred compounds of the present invention are as follows:
  • Salts of the compounds according to the invention are preferably pharmaceutically acceptable salts.
  • Other, non-pharmaceutically acceptable salts may be useful as intermediates e.g. in the preparation of pharmaceutically acceptable salts or other compound of the present invention.
  • compounds of the present invention and pharmaceutical acceptable salts thereof can also reduce the generation of inflammatory mediators.
  • the compounds can inhibit oxygen radical generation and generation of pro- inflammatory cytokines in monocytes.
  • the compounds are especially useful as inhibitors of one or more cytokines selected from LL-l ⁇ , TNF- ⁇ , GM-CSF or IL-8.
  • the compounds of the invention are indicated for use in medical therapy. More particularly, the compounds of the invention are indicated for use in the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS- degenerative disorders.
  • inflammatory and/or immunological disorders such as the oral or topical treatment of airway diseases involving inflammatory conditions, e.g. asthma, bronchitis or atopic diseases, e.g. rhinitis or atopic dermatitis; inflammatory bowel diseases, e.g. Crohn's disease or colitis; autoimmune diseases e.g.
  • multiple sclerosis diabetes, atherosclerosis, psoriasis, systemic lupus erythematosus or rheumatoid arthritis; malignant diseases, e.g. skin or lung cancer; HIV infections or AIDS; or for inhibiting rejection of organs/transplants.
  • the compounds of the invention are also indicated for use in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
  • the present invention is also directed to a method for the treatment of an inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorder, wherein a therapeutically effective amount of a compound of the invention is administered to a mammal in the need of such treatment.
  • the dose of the compound to be administered will depend upon the relevant indication, the age, weight and sex of the patient and may be determined by a physician.
  • the dosage will preferably be in the range of from 0.1 mg/kg to 100 mg/kg.
  • the compounds may be administered topically, e.g. to the lung and/or the airways, in the form of solutions, suspensions, aerosols or dry powder formulations, e.g. formulations in
  • the inhaler device known as the Turbuhaler (trademark of Astra AB of Sweden), or systemically, e.g. by oral administration in the form of tablets, pills, capsules, syrups, powders or granules, or by parenteral administration, e.g. in the form of sterile parenteral solutions or suspensions, or by rectal administration, e.g. in the form of suppositories.
  • Compounds of the invention may be administered on their own or as a pharmaceutical composition comprising a compound of the invention in combination with a pharmaceutically acceptable diluent, adjuvant or carrier.
  • Particularly preferred are compositions not containing material capable of causing an adverse, e.g. an allergic, reaction.
  • Dry powder formulations and pressurized HFA aerosols of the compounds of the invention may be administered by oral or nasal inhalation.
  • the compound is desirably finely divided.
  • the finely divided compound preferably has a mass median diameter of less than 10 ⁇ m, and may be suspended in a propellant mixture with the assistance of a disper- sant, such as a C 8 -C20 fatty acid or salt thereof, (e.g. oleic acid), a bile salt, aphospholipid, an alkyl saccharide, a perfluorinated or polyethoxylated surfactant, or other pharmaceutically acceptable dispersant.
  • a disper- sant such as a C 8 -C20 fatty acid or salt thereof, (e.g. oleic acid), a bile salt, aphospholipid, an alkyl saccharide, a perfluorinated or polyethoxylated surfactant, or other pharmaceutically acceptable dispersant.
  • Compounds of the invention may also be administered by means of a dry powder inhaler.
  • the inhaler may be a single or a multi dose inhaler, and may be a breath actuated dry powder inhaler.
  • a carrier substance e.g. a mono-, di- or polysaccharide, a sugar alcohol, or an other polyol.
  • Suitable carriers are sugars, e.g. lactose, glucose, raffinose, melezitose, lactitol, maltitol, trehalose, sucrose, mannitol; and starch.
  • the finely divided compound may be coated by another substance.
  • the powder mixture may also be dispensed into hard gelatine capsules, each containing the desired dose of the active compound.
  • Another possibility is to process the finely divided powder into spheres which break up during the inhalation procedure.
  • This spheronized powder may be filled into the drug
  • a ® reservoir of a multidose inhaler e.g. that known as the Turbuhaler in which a dosing unit meters the desired dose which is then inhaled by the patient.
  • the active compound with or without a carrier substance, is delivered to the patient.
  • the active compound may be admixed with an adjuvant or a carrier, e.g. lactose, saccharose, sorbitol, mannitol; a starch, e.g. potato starch, corn starch or amylopectin; a cellulose derivative; a binder, e.g. gelatine orpolyvinylpyrrolidone, and/or a lubricant, e.g. magnesium stearate, calcium stearate, polyethylene glycol, a wax, paraffin, and the like, and then compressed into tablets.
  • the cores, prepared as described above may be coated with a concentrated sugar solution which may contain e.g. gum arabic, gelatine, talcum, titanium dioxide, and the like.
  • the tablet may be coated with a suitable polymer dissolved in a readily volatile organic solvent.
  • the compound may be admixed with e.g. a vegetable oil or polyethylene glycol.
  • Hard gelatine capsules may contain granules of the compound using either the above mentioned excipients for tablets. Also liquid or semisolid formulations of the drug may be filled into hard gelatine capsules.
  • Liquid preparations for oral application may be in the form of syrups or suspensions, for solutions containing the compound, the balance being sugar and a mixture of ethanol, water, glycerol and propylene glycol.
  • Such liquid preparations may contain colouring agents, flavouring agents, saccharine and/or carboxymethylcellulose as a thickening agent or other excipients known to those skilled in art.
  • the compounds of the invention may also be administered in conjunction with other compounds used for the treatment of the above conditions.
  • 'medical therapy' as used herein is intended to include prophylactic, diagnostic and therapeutic regimens carried out in vivo or ex vivo on humans or other mammals.
  • Polymeric imidazolide carbamate (3g, 3.0 mmol, prepared as described by Hauske, J. R.; Dorff, P. Tetrahedron Lett. 1995, 36, 1589-1592, from a Wang resin purchased from Rapp Polymere GmbH, Tubingen, Germany, 1.1 mmol/g,) was heated in DMF ( 25 ml) containing 3-piperidine methanol (1.38g, 12 mmol) at 90 °C for 13h. The resin was filtered and washed (3 times, 30ml) DMF, CH 2 C1 2 , MeOH, and dried in vacuum. Gel-phase 13 C- nmr (CDC1 3 ) showed formation of carbamate linked 3-piperidine methanol.
  • Oxalylchloride (25.9 ml, 0.3 mol) in CH 2 C1 2 (133ml) was added droppwise to DMSO in CH 2 C1 2 (133ml) during 30 min, at -78°C. After additional 15 min s-collidine (79ml, 0.6 mmol) in CH C1 2 (133ml) was added during 20 min, and 15 min later a part of the cool activated DMSO-solution (50 ml, approx. 30 mmol) was added to the dried carbamate linked 3-piperidine methanol resin (approx. 3 mmol), and the mixture was shaken over night at room temperature.
  • N-alkyl-l,2-diaminobenzene resin 75mg, 0.058 mmol
  • l-ethylindole-3-glyoxylic acid 79 mg, 0.36 mmol
  • DMSO DMSO
  • step b) The product of step b) (0.142 g, 0.253 mmol) was suspended in tetrahydrofuran (1 ml) and aqueous methylamine (40%, 1 ml) was added. After stirring overnight the solvent was removed in vacuo. The residue was washed with water and treated with glacial acetic acid to obtain the title compound after freeze drying as a yellow solid (0.111 g, 99%).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne de nouvelles quinoxalinones inhibitrices de la protéine kinase C. L'invention concerne également des formulations renfermant ces inhibiteurs de la protéine kinase C, leur utilisation dans des thérapies médicales et pour la production d'un médicament destiné au traitement de troubles inflammatoires, immunologiques, broncho-pulmonaires, cardio-vasculaires ou oncologiques, ou de maladies dégénératives du SNC.
PCT/SE1999/000276 1998-03-13 1999-02-26 Nouveaux composes WO1999046260A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU28638/99A AU2863899A (en) 1998-03-13 1999-02-26 New compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9800836-0 1998-03-13
SE9800836A SE9800836D0 (sv) 1998-03-13 1998-03-13 New Compounds

Publications (1)

Publication Number Publication Date
WO1999046260A1 true WO1999046260A1 (fr) 1999-09-16

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ID=20410540

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1999/000276 WO1999046260A1 (fr) 1998-03-13 1999-02-26 Nouveaux composes

Country Status (3)

Country Link
AU (1) AU2863899A (fr)
SE (1) SE9800836D0 (fr)
WO (1) WO1999046260A1 (fr)

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004052854A2 (fr) * 2002-12-10 2004-06-24 Wyeth Derives d'acide 1h-indol-3-yl glyoxylique a substitution aryle, aryloxy et alkyloxy en tant qu'inhibiteurs de l'inhibiteur de l'activateur du plasminogene-1 (pai-1)
WO2005051957A1 (fr) * 2003-11-21 2005-06-09 Bayer Pharmaceuticals Corporation Derives d'indolyl-thieno`3,4-b!pyrazin-3-one utilises pour traiter les maladies et les troubles hyper-proliferatifs associes a l'angiogenese
WO2005067932A1 (fr) * 2004-01-06 2005-07-28 Janssen Pharmaceutica, N.V. Derives de (3-oxo-3, 4-dihydro-quinoxalin-2-yl-amino)-benzamide et composes afferents comme inhibiteurs de la glycogene phosphorylase dans le traitement du diabete et de l'obesite
US7056943B2 (en) 2002-12-10 2006-06-06 Wyeth Substituted indole oxo-acetyl amino acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7074817B2 (en) 2001-06-20 2006-07-11 Wyeth Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7078429B2 (en) 2002-12-10 2006-07-18 Wyeth Substituted 3-carbonyl-1H-indol-1-yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7101903B2 (en) 2002-12-10 2006-09-05 Wyeth Substituted dihydropyrano indole-3,4-dione derivatives as inhibitiors of plasminogen activator inhibitor-1 (PAI-1)
US7141592B2 (en) 2003-09-25 2006-11-28 Wyeth Substituted oxadiazolidinediones
US7163954B2 (en) 2003-09-25 2007-01-16 Wyeth Substituted naphthyl benzothiophene acids
US7186749B2 (en) 2004-08-23 2007-03-06 Wyeth Pyrrolo-naphthyl acids and methods for using them
US7265148B2 (en) 2003-09-25 2007-09-04 Wyeth Substituted pyrrole-indoles
US7268159B2 (en) 2003-09-25 2007-09-11 Wyeth Substituted indoles
US7332521B2 (en) 2003-09-25 2008-02-19 Wyeth Substituted indoles
US7342039B2 (en) 2003-09-25 2008-03-11 Wyeth Substituted indole oximes
US7348351B2 (en) 2002-12-10 2008-03-25 Wyeth Substituted 3-alkyl and 3-arylalkyl 1H-indol-1yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7351726B2 (en) 2003-09-25 2008-04-01 Wyeth Substituted oxadiazolidinediones
US7351730B2 (en) 2001-06-20 2008-04-01 Wyeth Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
US7411083B2 (en) 2003-09-25 2008-08-12 Wyeth Substituted acetic acid derivatives
US7420083B2 (en) 2003-09-25 2008-09-02 Wyeth Substituted aryloximes
US7442805B2 (en) 2003-09-25 2008-10-28 Wyeth Substituted sulfonamide-indoles
US7446201B2 (en) 2003-09-25 2008-11-04 Wyeth Substituted heteroaryl benzofuran acids
WO2008148867A2 (fr) 2007-06-08 2008-12-11 Novartis Ag Dérivés de la quinoxaline en tant qu'inhibiteurs de l'activité tyrosine kinase de kinases janus
US7534894B2 (en) 2003-09-25 2009-05-19 Wyeth Biphenyloxy-acids
US7582773B2 (en) 2003-09-25 2009-09-01 Wyeth Substituted phenyl indoles
WO2009109341A1 (fr) 2008-03-05 2009-09-11 Merck Patent Gmbh Dérivés de pyridopyrazinone comme stimulateurs de la sécrétion d’insuline, leurs procédés d’obtention et leur utilisation pour le traitement du diabète
US7605172B2 (en) 2004-08-23 2009-10-20 Wyeth Thiazolo-naphthyl acids
US7683091B2 (en) 2005-08-17 2010-03-23 Wyeth Substituted indoles and methods of their use
WO2010053757A1 (fr) * 2008-10-29 2010-05-14 Gilead Palo Alto, Inc. Inhibiteurs, à base de 2-oxoquinoxaline, des canaux sodiques tardifs
US7754747B2 (en) 2004-08-23 2010-07-13 Wyeth Llc Oxazolo-naphthyl acids
US20100216726A1 (en) * 2007-08-31 2010-08-26 Purdue Pharma L.P. Substituted-Quinoxaline-Type Piperidine Compounds and the Uses Thereof
WO2012085648A1 (fr) 2010-12-22 2012-06-28 Purdue Pharma L.P. Composés de pipéridine de type quinoxaline substitués par du phosphore et leurs utilisations
EP2537844A1 (fr) 2008-07-21 2012-12-26 Purdue Pharma L.P. Composés pipéridine à liaison et substitués par une quinoxaline, et leurs utilisations
WO2013080036A1 (fr) 2011-12-01 2013-06-06 Purdue Pharma L.P. Composés de pipéridine de type quinoxaline substituée par une azétidine et leurs utilisations
WO2014020405A1 (fr) 2012-07-30 2014-02-06 Purdue Pharma L.P. Composés de pipéridine cycliques de type quinoxaline substitués par un groupe dérivé d'urée ou un groupe dérivé de lactame et leurs utilisations
US8664379B2 (en) 2008-10-30 2014-03-04 Gilead Sciences, Inc. Fused heterocyclic compounds as ion channel modulators
WO2014102594A2 (fr) 2012-12-27 2014-07-03 Purdue Pharma L.P. Composés de pipéridine de type benzimidazole substitué et leurs utilisations
WO2014102589A1 (fr) 2012-12-27 2014-07-03 Purdue Pharma L.P. Composés de pipéridine du type quinazolin-4(3h)-one et utilisations de ceux-ci
WO2014102588A2 (fr) 2012-12-27 2014-07-03 Purdue Pharma L.P. Composés de pipéridine de type indole et indoline et leurs utilisations
WO2014102592A2 (fr) 2012-12-27 2014-07-03 Purdue Pharma L.P. Composés de pipéridine de type quinoxaline substituée par oxime et leurs utilisations

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CN114524805B (zh) * 2022-03-10 2023-01-24 浙江树人学院（浙江树人大学） 固体酸催化多组分反应在含氟药物制备中的应用

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WO1998013368A1 (fr) * 1996-09-25 1998-04-02 Astra Aktiebolag (Publ) Nouveaux composes pharmaceutiquement actifs

Patent Citations (1)

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WO1998013368A1 (fr) * 1996-09-25 1998-04-02 Astra Aktiebolag (Publ) Nouveaux composes pharmaceutiquement actifs

Cited By (80)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7074817B2 (en) 2001-06-20 2006-07-11 Wyeth Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7351730B2 (en) 2001-06-20 2008-04-01 Wyeth Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
US7368471B2 (en) 2001-06-20 2008-05-06 Wyeth Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7629377B2 (en) 2001-06-20 2009-12-08 Wyeth Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
US7101903B2 (en) 2002-12-10 2006-09-05 Wyeth Substituted dihydropyrano indole-3,4-dione derivatives as inhibitiors of plasminogen activator inhibitor-1 (PAI-1)
US7056943B2 (en) 2002-12-10 2006-06-06 Wyeth Substituted indole oxo-acetyl amino acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
JP2006510673A (ja) * 2002-12-10 2006-03-30 ワイス プラスミノゲンアクティベータインヒビター１（ｐａｉ−１）のインヒビターとしての、アリール、アリールオキシ、および、アルキルオキシ置換１ｈ−インドール−３−イルグリオキシル酸誘導体
US7078429B2 (en) 2002-12-10 2006-07-18 Wyeth Substituted 3-carbonyl-1H-indol-1-yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7348351B2 (en) 2002-12-10 2008-03-25 Wyeth Substituted 3-alkyl and 3-arylalkyl 1H-indol-1yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7566791B2 (en) 2002-12-10 2009-07-28 Wyeth Substituted 3-carbonyl-1h-indol-1yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7160918B2 (en) 2002-12-10 2007-01-09 Hassan Mahmoud Elokdah Substituted indole oxo-acetyl amino acetic acid derivatives as inhibitors of plasminogen activator inhibitor (PAI-1)
WO2004052854A2 (fr) * 2002-12-10 2004-06-24 Wyeth Derives d'acide 1h-indol-3-yl glyoxylique a substitution aryle, aryloxy et alkyloxy en tant qu'inhibiteurs de l'inhibiteur de l'activateur du plasminogene-1 (pai-1)
US7459478B2 (en) 2002-12-10 2008-12-02 Wyeth Substituted dihydropyrano indole-3,4-dione derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7674818B2 (en) 2002-12-10 2010-03-09 Wyeth Llc Aryl, aryloxy, alkyloxy substituted 1H-indol-3-yl glyoxylic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7259182B2 (en) 2002-12-10 2007-08-21 Wyeth Aryl, aryloxy, and aklyloxy substituted 1H-indol-3-yl glyoxylic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
WO2004052854A3 (fr) * 2002-12-10 2004-08-05 Wyeth Corp Derives d'acide 1h-indol-3-yl glyoxylique a substitution aryle, aryloxy et alkyloxy en tant qu'inhibiteurs de l'inhibiteur de l'activateur du plasminogene-1 (pai-1)
US7141592B2 (en) 2003-09-25 2006-11-28 Wyeth Substituted oxadiazolidinediones
US7411083B2 (en) 2003-09-25 2008-08-12 Wyeth Substituted acetic acid derivatives
US7342039B2 (en) 2003-09-25 2008-03-11 Wyeth Substituted indole oximes
US7268159B2 (en) 2003-09-25 2007-09-11 Wyeth Substituted indoles
US7351726B2 (en) 2003-09-25 2008-04-01 Wyeth Substituted oxadiazolidinediones
US7265148B2 (en) 2003-09-25 2007-09-04 Wyeth Substituted pyrrole-indoles
US7332521B2 (en) 2003-09-25 2008-02-19 Wyeth Substituted indoles
US7534894B2 (en) 2003-09-25 2009-05-19 Wyeth Biphenyloxy-acids
US7420083B2 (en) 2003-09-25 2008-09-02 Wyeth Substituted aryloximes
US7442805B2 (en) 2003-09-25 2008-10-28 Wyeth Substituted sulfonamide-indoles
US7446201B2 (en) 2003-09-25 2008-11-04 Wyeth Substituted heteroaryl benzofuran acids
US7582773B2 (en) 2003-09-25 2009-09-01 Wyeth Substituted phenyl indoles
US7803835B2 (en) 2003-09-25 2010-09-28 Wyeth Llc Substituted acetic acid derivatives
US7163954B2 (en) 2003-09-25 2007-01-16 Wyeth Substituted naphthyl benzothiophene acids
JP2007512331A (ja) * 2003-11-21 2007-05-17 バイエル・フアーマシユーチカルズ・コーポレーシヨン 過剰増殖性疾患および血管新生に関連した病気の治療に有用なインドリル−チエノ’３，４−ｂ！ピラジン−３−オン誘導体
WO2005051957A1 (fr) * 2003-11-21 2005-06-09 Bayer Pharmaceuticals Corporation Derives d'indolyl-thieno`3,4-b!pyrazin-3-one utilises pour traiter les maladies et les troubles hyper-proliferatifs associes a l'angiogenese
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