AP9901631A0 - Reverse hydroxamate derivatives as metalloprotease inhibitors. - Google Patents

Reverse hydroxamate derivatives as metalloprotease inhibitors.

Info

Publication number
AP9901631A0
AP9901631A0 APAP/P/1999/001631A AP9901631A AP9901631A0 AP 9901631 A0 AP9901631 A0 AP 9901631A0 AP 9901631 A AP9901631 A AP 9901631A AP 9901631 A0 AP9901631 A0 AP 9901631A0
Authority
AP
ARIPO
Prior art keywords
butyl
ethyl
hydrogen
tnf
sec
Prior art date
Application number
APAP/P/1999/001631A
Inventor
Marc W Andersen
Darryl Lynn Mcdougald
David Lee Musso
Michael Howard Rabinowitz
Jennifer Badiang Stanford
Robert William Wiethe
Original Assignee
Glaxo Group Ltd
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 Glaxo Group Ltd filed Critical Glaxo Group Ltd
Publication of AP9901631A0 publication Critical patent/AP9901631A0/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic 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
    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/60—Heterocyclic 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 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
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole 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
    • C07D277/38—Nitrogen atoms
    • C07D277/44—Acylated amino or imino radicals
    • C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/135—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Ophthalmology & Optometry (AREA)
  • Oncology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Detergent Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

A family of compounds having general structural formula (i)wherein w is a reverse hydroxamic acid group (a); r5 is hydrogen or lower alkyl; r6 is (b); where z1 is heteroarylen; preferably: r1 is methyl, ethyl, isopropyl, n-propyl or 3,3,3-trifluoro-n-propyl; r2 is isobutyl or sec-butyl; r3 is hydrogen; r4 is tert-butyl, sec-butyl, 1-methoxy-1-ethyl or 2-(2-pyridylcarbonylamino)-1-ethyl; r5 is hydrogen; and r6 is 2-thiazolyl or 2-pyridyl. Such compounds show potent inhibition of mmp's, cell-free tnf convertase enzyme and tnf release from cells, and in some cases inhibit tnf convertase and tnf release from cells in preference to matrix metalloprotease.
APAP/P/1999/001631A 1997-02-26 1998-02-24 Reverse hydroxamate derivatives as metalloprotease inhibitors. AP9901631A0 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3911297P 1997-02-26 1997-02-26
PCT/EP1998/001015 WO1998038179A1 (en) 1997-02-26 1998-02-24 Reverse hydroxamate derivatives as metalloprotease inhibitors

Publications (1)

Publication Number Publication Date
AP9901631A0 true AP9901631A0 (en) 1999-09-30

Family

ID=21903750

Family Applications (1)

Application Number Title Priority Date Filing Date
APAP/P/1999/001631A AP9901631A0 (en) 1997-02-26 1998-02-24 Reverse hydroxamate derivatives as metalloprotease inhibitors.

Country Status (16)

Country Link
EP (1) EP1019386A1 (en)
JP (1) JP2001513767A (en)
KR (1) KR20000075681A (en)
AP (1) AP9901631A0 (en)
AR (1) AR013070A1 (en)
AU (1) AU6822398A (en)
BR (1) BR9807763A (en)
CA (1) CA2281664A1 (en)
HR (1) HRP980096A2 (en)
IS (1) IS5159A (en)
NO (1) NO994103L (en)
PE (1) PE59199A1 (en)
PL (1) PL335378A1 (en)
TR (1) TR199902063T2 (en)
WO (1) WO1998038179A1 (en)
ZA (1) ZA981532B (en)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6294573B1 (en) 1997-08-06 2001-09-25 Abbott Laboratories Reverse hydroxamate inhibitors of matrix metalloproteinases
US6235786B1 (en) 1997-08-06 2001-05-22 Abbott Laboratories Reverse hydroxamate inhibitors of matrix metalloproteinases
PL194240B1 (en) 1998-02-07 2007-05-31 British Biotech Pharm Antibacterial agents
WO2000012083A1 (en) * 1998-08-26 2000-03-09 Glaxo Group Limited Formamides as therapeutic agents
GB9818621D0 (en) * 1998-08-26 1998-10-21 Glaxo Group Ltd Formamide compounds as therapeutic agents
WO2000012466A1 (en) * 1998-08-26 2000-03-09 Glaxo Group Limited Formamide compounds as therapeutic agents
US6288261B1 (en) 1998-12-18 2001-09-11 Abbott Laboratories Inhibitors of matrix metalloproteinases
US6329550B1 (en) 1998-12-31 2001-12-11 Aventis Pharmaceuticals Inc. Amidomalonamides useful as inhibitors of MMP of matrix metalloproteinase
GB9918869D0 (en) * 1999-08-10 1999-10-13 British Biotech Pharm Antibacterial agents
JP2003081838A (en) * 2001-09-11 2003-03-19 Rohto Pharmaceut Co Ltd Glucosamine preparation
US7011854B2 (en) 2002-02-04 2006-03-14 Alfama-Investigacao e Desenvolvimento de Produtos Farmaceuticos Lda Method for treating a mammal by administration of a compound having the ability to release CO, compounds having the ability to release CO and pharmaceutical compositions thereof
EP1622617A2 (en) * 2003-02-11 2006-02-08 Boehringer Ingelheim International Gmbh New pharmaceutical compositions based on anticholinergics and tace-inhibitors
WO2007092899A2 (en) * 2006-02-09 2007-08-16 The Burnham Institute Inhibitors of membrane type-1 matrix metalloproteinase for the treatment of insulin-dependent diabetes mellitus
EP2234608A2 (en) 2007-12-11 2010-10-06 Viamet Pharmaceuticals, Inc. Metalloenzyme inhibitors using metal binding moieties in combination with targeting moieties
EP2105164B1 (en) 2008-03-25 2011-01-12 Affectis Pharmaceuticals AG Novel P2X7R antagonists and their use
EP2243772B1 (en) 2009-04-14 2012-01-18 Affectis Pharmaceuticals AG Novel P2X7R antagonists and their use
WO2012110190A1 (en) 2011-02-17 2012-08-23 Affectis Pharmaceuticals Ag Novel p2x7r antagonists and their use
WO2012145520A2 (en) 2011-04-19 2012-10-26 Alfama, Inc. Carbon monoxide releasing molecules and uses thereof
WO2012163456A1 (en) 2011-05-27 2012-12-06 Affectis Pharmaceuticals Ag Novel p2x7r antagonists and their use
WO2012163792A1 (en) 2011-05-27 2012-12-06 Affectis Pharmaceuticals Ag Novel p2x7r antagonists and their use
WO2013013179A1 (en) 2011-07-21 2013-01-24 Alfama, Inc. Ruthenium carbon monoxide releasing molecules and uses thereof
EP3860608A1 (en) 2018-10-04 2021-08-11 INSERM (Institut National de la Santé et de la Recherche Médicale) Egfr inhibitors for treating keratodermas

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9223904D0 (en) * 1992-11-13 1993-01-06 British Bio Technology Inhibition of cytokine production
US6037472A (en) * 1993-11-04 2000-03-14 Syntex (U.S.A.) Inc. Matrix metalloprotease inhibitors
EP0822186B1 (en) * 1994-01-20 2000-03-15 British Biotech Pharmaceuticals Limited L-tert-leucine-2-pyridylamide
GB9514867D0 (en) * 1995-07-20 1995-09-20 British Biotech Pharm Metalloproteinase inhibitors
HUP9903863A3 (en) * 1995-11-23 2000-11-28 British Biotech Pharm Metalloproteinase inhibitors

Also Published As

Publication number Publication date
IS5159A (en) 1999-08-20
PE59199A1 (en) 1999-06-24
TR199902063T2 (en) 1999-12-21
WO1998038179A1 (en) 1998-09-03
AR013070A1 (en) 2000-12-13
PL335378A1 (en) 2000-04-25
EP1019386A1 (en) 2000-07-19
JP2001513767A (en) 2001-09-04
NO994103D0 (en) 1999-08-25
HRP980096A2 (en) 1998-12-31
KR20000075681A (en) 2000-12-26
BR9807763A (en) 2000-02-22
CA2281664A1 (en) 1998-09-03
ZA981532B (en) 1999-08-24
NO994103L (en) 1999-10-25
AU6822398A (en) 1998-09-18

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