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WO2000049007A8 - Derives acetamido acetonitriles en tant qu'inhibiteurs de la cathepsine l et/ou s - Google Patents

Derives acetamido acetonitriles en tant qu'inhibiteurs de la cathepsine l et/ou s

Info

Publication number
WO2000049007A8
WO2000049007A8 PCT/GB2000/000532 GB0000532W WO0049007A8 WO 2000049007 A8 WO2000049007 A8 WO 2000049007A8 GB 0000532 W GB0000532 W GB 0000532W WO 0049007 A8 WO0049007 A8 WO 0049007A8
Authority
WO
WIPO (PCT)
Prior art keywords
cathepsin
compound
formula
medicament
acetamido
Prior art date
Application number
PCT/GB2000/000532
Other languages
English (en)
Other versions
WO2000049007A1 (fr
Inventor
Howard Tucker
Michael Stewart Large
John Oldfield
Craig Johnstone
Philip Neil Edwards
Original Assignee
Astrazeneca Ab
Howard Tucker
Michael Stewart Large
John Oldfield
Craig Johnstone
Philip Neil Edwards
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
Priority claimed from GBGB9903857.2A external-priority patent/GB9903857D0/en
Priority claimed from GBGB9916098.8A external-priority patent/GB9916098D0/en
Application filed by Astrazeneca Ab, Howard Tucker, Michael Stewart Large, John Oldfield, Craig Johnstone, Philip Neil Edwards filed Critical Astrazeneca Ab
Priority to JP2000599747A priority Critical patent/JP2002537293A/ja
Priority to EP00903848A priority patent/EP1155010A1/fr
Priority to AU25603/00A priority patent/AU2560300A/en
Publication of WO2000049007A1 publication Critical patent/WO2000049007A1/fr
Publication of WO2000049007A8 publication Critical patent/WO2000049007A8/fr

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/12Drugs for disorders of the metabolism for electrolyte homeostasis
    • A61P3/14Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
    • 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
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00Carboxylic acid nitriles
    • C07C255/01Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
    • C07C255/29Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups and acylated amino groups bound to the carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57Nitriles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D231/18One oxygen or sulfur atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
    • C07D233/84Sulfur atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/54Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D333/00Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04Ortho-condensed systems

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Furan Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pyrrole Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)

Abstract

L'invention concerne un composé correspondant à la formule (I) dans laquelle Ar, R?1, R2, R3, R4 et R5¿ possèdent les notations données dans la description. Elle concerne également une composition comprenant un composé correspondant à la formule (I) ainsi qu'un excipient ou diluant; elle concerne encore l'emploi d'un composé correspondant à la formule (I) à dans la fabrication d'un médicament utile pour inhiber une cystéine protéase chez un animal de sang chaud, l'emploi d'un tel composé dans la fabrication d'un médicament utile dans le traitement du syndrome respiratoire obstructif chronique, chez un animal de sang chaud, ainsi qu'un procédé de traitement d'une pathologie induite par la cathepsine L ou S, consistant à administrer à un mammifère nécessitant un tel traitement une dose efficace d'un composé correspondant à la formule (I).
PCT/GB2000/000532 1999-02-20 2000-02-16 Derives acetamido acetonitriles en tant qu'inhibiteurs de la cathepsine l et/ou s WO2000049007A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2000599747A JP2002537293A (ja) 1999-02-20 2000-02-16 カテプシンlおよび/またはカテプシンsの阻害剤としてのアセタミドアセトニトリル誘導体
EP00903848A EP1155010A1 (fr) 1999-02-20 2000-02-16 Derives acetamido acetonitriles en tant qu'inhibiteurs de la cathepsine l et/ou s
AU25603/00A AU2560300A (en) 1999-02-20 2000-02-16 Acetamido acetonitrile derivatives as inhibitors of cathepsin l and/or cathepsins

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9903857.2A GB9903857D0 (en) 1999-02-20 1999-02-20 Chemical compounds
GB9916098.8 1999-07-10
GB9903857.2 1999-07-10
GBGB9916098.8A GB9916098D0 (en) 1999-07-10 1999-07-10 Chemical compounds

Publications (2)

Publication Number Publication Date
WO2000049007A1 WO2000049007A1 (fr) 2000-08-24
WO2000049007A8 true WO2000049007A8 (fr) 2001-03-15

Family

ID=26315158

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2000/000532 WO2000049007A1 (fr) 1999-02-20 2000-02-16 Derives acetamido acetonitriles en tant qu'inhibiteurs de la cathepsine l et/ou s

Country Status (4)

Country Link
EP (1) EP1155010A1 (fr)
JP (1) JP2002537293A (fr)
AU (1) AU2560300A (fr)
WO (1) WO2000049007A1 (fr)

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US6395897B1 (en) * 1999-03-02 2002-05-28 Boehringer Ingelheim Pharmaceuticals, Inc. Nitrile compounds useful as reversible inhibitors of #9 cathepsin 5
NZ514234A (en) 1999-03-15 2004-02-27 Axys Pharm Inc N-cyanomethylamides as protease inhibitors
SI1178958T1 (en) * 1999-03-15 2004-08-31 Axys Pharmaceuticals, Inc. N-cyanomethyl amides as protease inhibitors
US6525036B2 (en) * 2000-01-06 2003-02-25 Merck & Co., Inc. Compounds and compositions as protease inhibitors
GB0003111D0 (en) 2000-02-10 2000-03-29 Novartis Ag Organic compounds
US6812237B2 (en) 2000-05-15 2004-11-02 Novartis Ag N-substituted peptidyl nitriles as cysteine cathepsin inhibitors
ES2249482T3 (es) * 2000-05-15 2006-04-01 Novartis Ag Peptidilnitrilos n-sustituidos como inhibidores de cisteina catepsinas.
WO2002050052A1 (fr) * 2000-12-20 2002-06-27 Syngenta Participations Ag N-acyl aminoacetonitriles aux proprietes pesticides
US7030116B2 (en) 2000-12-22 2006-04-18 Aventis Pharmaceuticals Inc. Compounds and compositions as cathepsin inhibitors
CA2433520A1 (fr) 2000-12-22 2002-07-04 Axys Pharmaceuticals, Inc. Composes et compositions en tant qu'inhibiteurs de cathepsine
JP4365094B2 (ja) 2001-03-02 2009-11-18 メルク フロスト カナダ リミテツド カテプシンシステインプロテアーゼ阻害薬
US6982263B2 (en) * 2001-06-08 2006-01-03 Boehringer Ingelheim Pharmaceuticals, Inc. Nitriles useful as reversible inhibitors of cysteine proteases
CN1324008C (zh) 2001-09-14 2007-07-04 安万特药物公司 作为组织蛋白酶抑制剂的新化合物和组合物
WO2003042197A1 (fr) 2001-11-14 2003-05-22 Aventis Pharmaceuticals Inc. Nouveaux composes et compositions jouant le role d'inhibiteurs de cathepsine s
DK1482924T3 (da) 2002-03-05 2008-09-29 Merck Frosst Canada Ltd Cathepsin-cystein-protease-inhibotorer
US6878706B1 (en) 2002-04-05 2005-04-12 Boehringer Ingelheim Pharmaceuticals Inc. Cyanamides useful as reversible inhibitors of cysteine proteases
JP2005522489A (ja) * 2002-04-05 2005-07-28 ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド システインプロテアーゼの可逆性インヒビターとして有用なシアナミド
KR100962972B1 (ko) 2002-07-26 2010-06-09 주식회사유한양행 1-페닐피페리딘-3-온 유도체 및 그의 제조방법
EP1537074B1 (fr) * 2002-09-04 2019-02-27 Merck Canada Inc. Inhibiteurs de proteases a cysteine de type cathepsine
PL408347A1 (pl) 2002-09-24 2014-08-18 Novartis Ag Kombinacja, zastosowanie kombinacji oraz zastosowanie agonisty receptora S1P
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CA2610014A1 (fr) * 2005-06-02 2006-12-07 Merck Frosst Canada Ltd. Derives de fluoroalkylamine utilises comme inhibiteurs de la cathepsine
US20080227863A1 (en) * 2005-07-25 2008-09-18 Novartis Ag Organic Compounds
EP2240491B1 (fr) 2008-01-09 2015-07-15 Amura Therapeutics Limited DÉRIVÉS DE TÉTRAHYDROFURO(2,3-b)PYRROL-3-ONE COMME INHIBITEURS DE CYSTÉINE PROTÉINASES
CA2728514C (fr) 2008-06-20 2020-08-11 Novartis Ag Compositions pediatriques pour le traitement de la sclerose en plaques
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Also Published As

Publication number Publication date
WO2000049007A1 (fr) 2000-08-24
JP2002537293A (ja) 2002-11-05
EP1155010A1 (fr) 2001-11-21
AU2560300A (en) 2000-09-04

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