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PE20000725A1 - ALCOXYPYRROLIDINONE COMPOUNDS AS PROTEASE INHIBITORS - Google Patents

ALCOXYPYRROLIDINONE COMPOUNDS AS PROTEASE INHIBITORS

Info

Publication number
PE20000725A1
PE20000725A1 PE1999000518A PE00051899A PE20000725A1 PE 20000725 A1 PE20000725 A1 PE 20000725A1 PE 1999000518 A PE1999000518 A PE 1999000518A PE 00051899 A PE00051899 A PE 00051899A PE 20000725 A1 PE20000725 A1 PE 20000725A1
Authority
PE
Peru
Prior art keywords
alkyl
compounds
het
alcoxypyrrolidinone
preferred
Prior art date
Application number
PE1999000518A
Other languages
Spanish (es)
Inventor
Andrew D Gribble
Ashley E Fenwick
Marquis
Jason Witherington
Original Assignee
Smithkline Beecham Plc
Smithkline Beecham Corp
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 Plc, Smithkline Beecham Corp filed Critical Smithkline Beecham Plc
Publication of PE20000725A1 publication Critical patent/PE20000725A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24Oxygen or sulfur atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Physical Education & Sports Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

SE REFIERE A COMPUESTOS ALCOXIPIRROLIDINONA DE FORMULA I, DONDE X ES O, S, SO, SO2; Y ES H2, O; R1 ES H, ALQUILO C1-C6, ALQUENILO C2-C6, (CH2)(0-6)CO2R", DE PREFERENCIA GRUPO a, b; R" ES H, ALQUILO C1-C6, ALQUENILO C2-C6, Ar-ALQUILO C0-C6, ENTRE OTROS; R2 ES H, ALQUILO C1-C6, HET-ALQUILO C0-C6, DE PREFERENCIA ISOBUTILO, ENTRE OTROS; R3 ES H, ALQUILO C1-C6, ALQUENILO C2-C6, ALQUINILO C2-C6, DE PREFERENCIA GRUPO c, d; Ar ES FENILO, NAFTILO, OPCIONALMENTE SUSTITUIDO CON Ph-ALQUILO C0-C6, HET-ALQUILO C0-C6, O(CH2)(1-6)NR`R', ENTRE OTROS; R' ES H, ALQUILO C1-C6, ENTRE OTROS; HET ES UN ANILLO HETEROCICLICO BICICLICO DE 7-10 MIEMBROS, ANILLO MONICICLICO DE 5-7 MIEMBROS OPCIONALMENTE SUSTITUIDO CON OR', N(R')2, SR'CF3, ENTRE OTROS. SON COMPUESTOS PREFERIDOS 3-BENCILOXI-1-(N-CARBOBENCILOXI-L-LEUCINIL)PIRROLIDIN-4-ONA, 1-[2-(BENCILOXICARBONILAMINO)-4-METILPENTIL]-3-BENCILTIO-4-HIDROXIPIRROLIDINA, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA CONVERTIR 3-BENCILOXI-4-HIDROXI-1-(N-CARBOBENCILOXI-L-LEUCINIL)PIRROLIDONA, ENTRE OTROS EN UN COMPUESTO DE FORMULA I. EL COMPUESTO I ES UN INHIBIDOR DE CISTEINA-PROTEASAS (CATEPSINA K) POR LO QUE PUEDE SER UTIL PARA EL TRATAMIENTO DE ENFERMEDADES RELACIONADAS CON UNA EXCESIVA DEGRADACION DE HUESO O CARTILAGO COMO OSTEOPOROSIS, PERIODONTITIS, ARTRITIS, ENFERMEDAD GINGIVAL O PERIODONTALREFERS TO ALCOXYPYRROLIDINONE COMPOUNDS OF FORMULA I, WHERE X IS O, S, SO, SO2; Y IS H2, O; R1 IS H, C1-C6 ALKYL, C2-C6 ALKENYL, (CH2) (0-6) CO2R ", PREFERRED GROUP a, b; R" IS H, C1-C6 ALKYL, C2-C6 ALKENYL, Ar-ALKYL C0-C6, AMONG OTHERS; R2 IS H, C1-C6 ALKYL, HET-C0-C6 ALKYL, PREFERRED ISOBUTYL, AMONG OTHERS; R3 IS H, C1-C6 ALKYL, C2-C6 ALKYL, C2-C6 ALKYNYL, PREFERRED GROUP c, d; Ar IS PHENYL, NAPHTHYL, OPTIONALLY SUBSTITUTED WITH Ph-ALKYL C0-C6, HET-ALKYL C0-C6, O (CH2) (1-6) NR`R ', AMONG OTHERS; R 'IS H, C1-C6 ALKYL, AMONG OTHERS; HET IS A 7-10 MEMBER HETERO CYCLIC BICYCLE RING, 5-7 MEMBER MONICYCLE RING OPTIONALLY SUBSTITUTED WITH OR ', N (R') 2, SR'CF3, AMONG OTHERS. PREFERRED COMPOUNDS ARE 3-BENZYLLOXY-1- (N-CARBOBENZYLOXY-L-LEUKINYL) PYRROLIDIN-4-ONA, 1- [2- (BENZYLOXYCARBONYLAMINE) -4-METHYLPENTIL] -3-BENZYLTHI-4-HYDROXYPYRROLIDINE, BETWEEN. IT ALSO REFERS TO A PROCEDURE TO CONVERT 3-BENZYLOXY-4-HYDROXY-1- (N-CARBOBENZYLOXY-L-LEUKINYL) PYRROLIDONE, AMONG OTHERS, INTO A COMPOUND OF FORMULA I. COMPOUND I IS A CYSTEIN PROTEIN-PROTEIN INHIBITOR K) SO IT MAY BE USEFUL FOR THE TREATMENT OF DISEASES RELATED TO EXCESSIVE DEGRADATION OF THE BONE OR CARTILAGE SUCH AS OSTEOPOROSIS, PERIODONTITIS, ARTHRITIS, GINGIVAL OR PERIODONTAL DISEASE

PE1999000518A 1998-06-12 1999-06-11 ALCOXYPYRROLIDINONE COMPOUNDS AS PROTEASE INHIBITORS PE20000725A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US8905698P 1998-06-12 1998-06-12

Publications (1)

Publication Number Publication Date
PE20000725A1 true PE20000725A1 (en) 2000-09-28

Family

ID=22215426

Family Applications (1)

Application Number Title Priority Date Filing Date
PE1999000518A PE20000725A1 (en) 1998-06-12 1999-06-11 ALCOXYPYRROLIDINONE COMPOUNDS AS PROTEASE INHIBITORS

Country Status (10)

Country Link
EP (1) EP1086083A4 (en)
JP (1) JP2002517485A (en)
AR (1) AR018652A1 (en)
AU (1) AU4564499A (en)
CA (1) CA2334652A1 (en)
CO (1) CO5040090A1 (en)
DZ (1) DZ2815A1 (en)
MA (1) MA24877A1 (en)
PE (1) PE20000725A1 (en)
WO (1) WO1999064399A1 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030144175A1 (en) 1998-12-23 2003-07-31 Smithkline Beecham Corporation Protease inhibitors
EP1232154A4 (en) 1999-11-10 2004-06-23 Smithkline Beecham Corp Protease inhibitors
AU1474801A (en) 1999-11-10 2001-06-06 Smithkline Beecham Corporation Protease inhibitors
AU1588901A (en) 1999-11-10 2001-06-06 Smithkline Beecham Corporation Protease inhibitors
AU4344101A (en) 2000-03-21 2001-10-03 Smithkline Beecham Corp Protease inhibitors
WO2002080920A1 (en) * 2001-04-06 2002-10-17 Axys Pharmaceuticals, Inc. Arylacetamido-ketobenzoxazole as cysteine protease inhibitors
EP1465862A1 (en) 2002-01-17 2004-10-13 SmithKline Beecham Corporation Cycloalkyl ketoamides derivatives useful as cathepsin k inhibitors
WO2009087379A2 (en) 2008-01-09 2009-07-16 Amura Therapeutics Limited Tetrahydrofuro (3, 2 -b) pyrrol- 3 -one derivatives as inhibitors of cysteine proteinases
CN117940420A (en) 2021-09-14 2024-04-26 勃林格殷格翰国际有限公司 3-Phenoxyazetidin-1-yl-heteroaryl pyrrolidine derivatives and their use as pharmaceuticals

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0739204A4 (en) * 1993-11-09 2000-03-15 Merck & Co Inc PIPERIDINES, PYRROLIDINES AND HEXAHYDRO-1H-AZEPINES PROMOTING THE RELEASE OF GROWTH HORMONE
US5770573A (en) * 1993-12-06 1998-06-23 Cytel Corporation CS-1 peptidomimetics, compositions and methods of using the same
US5618792A (en) * 1994-11-21 1997-04-08 Cortech, Inc. Substituted heterocyclic compounds useful as inhibitors of (serine proteases) human neutrophil elastase

Also Published As

Publication number Publication date
MA24877A1 (en) 1999-12-31
EP1086083A1 (en) 2001-03-28
CO5040090A1 (en) 2001-05-29
AR018652A1 (en) 2001-11-28
DZ2815A1 (en) 2003-12-01
WO1999064399A1 (en) 1999-12-16
AU4564499A (en) 1999-12-30
CA2334652A1 (en) 1999-12-16
EP1086083A4 (en) 2001-09-26
JP2002517485A (en) 2002-06-18

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