WO1997018207A3 - Novel macrocyclic compounds as metalloprotease inhibitors - Google Patents

Novel macrocyclic compounds as metalloprotease inhibitors Download PDF

Info

Publication number
WO1997018207A3
WO1997018207A3 PCT/US1996/018382 US9618382W WO9718207A3 WO 1997018207 A3 WO1997018207 A3 WO 1997018207A3 US 9618382 W US9618382 W US 9618382W WO 9718207 A3 WO9718207 A3 WO 9718207A3
Authority
WO
WIPO (PCT)
Prior art keywords
compounds
macrocyclic compounds
metalloprotease inhibitors
inhibitors
novel macrocyclic
Prior art date
Application number
PCT/US1996/018382
Other languages
French (fr)
Other versions
WO1997018207A2 (en
Inventor
Chu-Biao Xue
Robert Joseph Cherney
Carl Peter Decicco
William Frank Degrado
Xiaohua He
Carl Nicolas Hodge
Irina Cipora Jacobson
Ronald Louis Magolda
Elizabeth Catherine Arner
Jingwu Duan
David J Nelson
Original Assignee
Du Pont Merck Pharma
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 to JP9519119A priority Critical patent/JP2000502050A/en
Priority to IL12436696A priority patent/IL124366A0/en
Priority to EE9800115A priority patent/EE9800115A/en
Priority to EA199800372A priority patent/EA199800372A1/en
Priority to SI9620120A priority patent/SI9620120A/en
Priority to KR1019980703618A priority patent/KR19990067592A/en
Priority to EP96943497A priority patent/EP0863885A2/en
Priority to SK634-98A priority patent/SK63498A3/en
Application filed by Du Pont Merck Pharma filed Critical Du Pont Merck Pharma
Priority to BR9611563A priority patent/BR9611563A/en
Priority to AU12726/97A priority patent/AU1272697A/en
Publication of WO1997018207A2 publication Critical patent/WO1997018207A2/en
Publication of WO1997018207A3 publication Critical patent/WO1997018207A3/en
Priority to NO982185A priority patent/NO982185L/en
Priority to LVP-98-104A priority patent/LV12167B/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic 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
    • C07D231/12—Heterocyclic 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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic 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
    • C07D233/56—Heterocyclic 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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D245/00—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms
    • C07D245/02—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D255/00—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00
    • C07D255/02—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00 not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D291/00—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms
    • C07D291/02—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms not condensed with other rings
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
    • C07D419/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D419/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/0606—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Rheumatology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

This invention relates to macrocyclic molecules which inhibit metalloproteinases, including aggrecanase, and the production of tumor necrosis factor (TNF). In particular, the compounds are inhibitors of metalloproteinases involved in tissue degradation and inhibitors of the release of tumor necrosis factor. The present invention also relates to pharmaceutical compositions comprising such compounds and to methods of using these compounds for the treatment of inflammatory diseases.
PCT/US1996/018382 1995-11-14 1996-11-13 Novel macrocyclic compounds as metalloprotease inhibitors WO1997018207A2 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
EP96943497A EP0863885A2 (en) 1995-11-14 1996-11-13 Novel macrocyclic compounds as metalloprotease inhibitors
EE9800115A EE9800115A (en) 1995-11-14 1996-11-13 Novel macrocyclic compounds as metalloprotease inhibitors
EA199800372A EA199800372A1 (en) 1995-11-14 1996-11-13 NEW MICROCYCLIC COMPOUNDS INHIBITORS
SI9620120A SI9620120A (en) 1995-11-14 1996-11-13 Novel macrocyclic compounds as metalloprotease inhibitors
KR1019980703618A KR19990067592A (en) 1995-11-14 1996-11-13 Novel Macrocyclic Compound as Metalloprotease Inhibitor
JP9519119A JP2000502050A (en) 1995-11-14 1996-11-13 New macrocyclic compounds as metalloprotease inhibitors
SK634-98A SK63498A3 (en) 1995-11-14 1996-11-13 Novel macrocyclic compounds as metalloprotease inhibitors
IL12436696A IL124366A0 (en) 1995-11-14 1996-11-13 Novel macrocyclic compounds as metalloprotease inhibitors
BR9611563A BR9611563A (en) 1995-11-14 1996-11-13 Compound pharmaceutical composition method of treating an inflammatory disease and assay to detect agrecanase inhibitors
AU12726/97A AU1272697A (en) 1995-11-14 1996-11-13 Novel macrocyclic compounds as metalloprotease inhibitors
NO982185A NO982185L (en) 1995-11-14 1998-05-13 Novel macrocyclic compounds as metalloproteinase inhibitors
LVP-98-104A LV12167B (en) 1995-11-14 1998-07-07 Novel macrocyclic compounds as metalloprotease inhibitors

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US668495P 1995-11-14 1995-11-14
US60/006,684 1995-11-14
US64690296A 1996-05-08 1996-05-08
US60/646,902 1996-05-08
US74343996A 1996-11-01 1996-11-01
US08/743,439 1996-11-01

Publications (2)

Publication Number Publication Date
WO1997018207A2 WO1997018207A2 (en) 1997-05-22
WO1997018207A3 true WO1997018207A3 (en) 1997-07-24

Family

ID=27358171

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/018382 WO1997018207A2 (en) 1995-11-14 1996-11-13 Novel macrocyclic compounds as metalloprotease inhibitors

Country Status (17)

Country Link
EP (1) EP0863885A2 (en)
JP (1) JP2000502050A (en)
CN (1) CN1202161A (en)
BR (1) BR9611563A (en)
CA (1) CA2237524A1 (en)
CZ (1) CZ144798A3 (en)
EE (1) EE9800115A (en)
HR (1) HRP960533A2 (en)
HU (1) HUP0201479A2 (en)
IL (1) IL124366A0 (en)
LV (1) LV12167B (en)
MX (1) MX9803851A (en)
NO (1) NO982185L (en)
PL (1) PL326714A1 (en)
SI (1) SI9620120A (en)
SK (1) SK63498A3 (en)
WO (1) WO1997018207A2 (en)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6281352B1 (en) 1995-11-14 2001-08-28 Dupont Pharmaceuticals Company Macrocyclic compounds as metalloprotease inhibitors
US5985911A (en) * 1997-01-07 1999-11-16 Abbott Laboratories C-terminal ketone inhibitors of matrix metalloproteinases and TNFα secretion
US5952320A (en) * 1997-01-07 1999-09-14 Abbott Laboratories Macrocyclic inhibitors of matrix metalloproteinases and TNFα secretion
ZA9820B (en) * 1997-01-07 1998-07-02 Abbott Lab Macrocyclic inhibitors of matrix metalloproteinases and tnf x secretion
US6548663B1 (en) 1998-03-31 2003-04-15 Bristol-Myers Squibb Pharma Company Benzodiazepine vitronectin receptor antagonist pharmaceuticals
JP4487019B2 (en) 1998-03-31 2010-06-23 ランサス メディカル イメージング インコーポレイテッド Drugs for imaging angiogenic diseases
US6524553B2 (en) 1998-03-31 2003-02-25 Bristol-Myers Squibb Pharma Company Quinolone vitronectin receptor antagonist pharmaceuticals
US6537520B1 (en) 1998-03-31 2003-03-25 Bristol-Myers Squibb Pharma Company Pharmaceuticals for the imaging of angiogenic disorders
WO1999064406A1 (en) 1998-06-11 1999-12-16 Du Pont Pharmaceuticals Company A process for the preparation of macrocyclic metalloprotease inhibitors
NZ525513A (en) 1998-08-07 2004-09-24 Pont Pharmaceuticals Du Succinoylamino lactams as inhibitors of Abeta protein production
HRP990246A2 (en) 1998-08-07 2000-06-30 Du Pont Pharm Co Succinoylamino benzodiazepines as inhibitors of a beta protein production
US6288261B1 (en) 1998-12-18 2001-09-11 Abbott Laboratories Inhibitors of matrix metalloproteinases
AU766822B2 (en) 1998-12-18 2003-10-23 Du Pont Pharmaceuticals Company Vitronectin receptor antagonist pharmaceuticals
US6511649B1 (en) 1998-12-18 2003-01-28 Thomas D. Harris Vitronectin receptor antagonist pharmaceuticals
WO2000035887A2 (en) 1998-12-18 2000-06-22 Du Pont Pharm Co Vitronectin receptor antagonist pharmaceuticals
US6794518B1 (en) 1998-12-18 2004-09-21 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6569402B1 (en) 1998-12-18 2003-05-27 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6649377B1 (en) 1999-05-10 2003-11-18 Syntex (U.S.A.) Llc Human aggrecanase and nucleic acid compositions encoding the same
US6808902B1 (en) 1999-11-12 2004-10-26 Amgen Inc. Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules
US6989139B2 (en) * 2000-02-15 2006-01-24 Bristol-Myers Squibb Pharma Company Matrix metalloproteinase inhibitors
WO2001092235A1 (en) 2000-06-01 2001-12-06 Bristol-Myers Squibb Pharma Company LACTAMS SUBSTITUTED BY CYCLIC SUCCINATES AS INHIBITORS OF Aβ PROTEIN PRODUCTION
PT2087908T (en) 2001-06-26 2018-07-16 Amgen Inc Antibodies to opgl
PE20030701A1 (en) 2001-12-20 2003-08-21 Schering Corp COMPOUNDS FOR THE TREATMENT OF INFLAMMATORY DISORDERS
US7491794B2 (en) 2003-10-14 2009-02-17 Intermune, Inc. Macrocyclic compounds as inhibitors of viral replication
JPWO2005044780A1 (en) * 2003-11-10 2007-05-17 杏林製薬株式会社 Aminocarboxylic acid derivatives and their addition salts and S1P receptor modulators
CA2708281A1 (en) 2007-12-11 2009-08-27 Viamet Pharmaceuticals, Inc. Metalloenzyme inhibitors using metal binding moieties in combination with targeting moieties
US8476305B2 (en) 2008-02-07 2013-07-02 Kyorin Pharmaceutical Co., Ltd. Therapeutic agent or prophylactic agent for inflammatory bowel disease comprising amino alcohol derivative as active ingredient
WO2010132494A1 (en) * 2009-05-11 2010-11-18 Ghosh Arun K Compounds and methods for treating aids and hiv infections
WO2012156756A2 (en) 2011-05-19 2012-11-22 Centro Nacional De Investigaciones Oncológicas (Cnio) New compounds
CN102276546B (en) * 2011-05-31 2014-06-25 中国科学院广州生物医药与健康研究院 Compound used as aggrecanase modifier and application thereof
CN108727293B (en) * 2016-09-18 2021-05-11 广西师范大学 1,2, 8-oxo diazacyclononane-9-one derivative and synthetic method thereof
AU2019352741A1 (en) 2018-10-04 2021-05-06 Assistance Publique-Hôpitaux De Paris (Aphp) EGFR inhibitors for treating keratodermas

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992013831A1 (en) * 1991-02-07 1992-08-20 British Bio-Technology Limited Hydroxamic acid derivatives, process for their preparation and use thereof
US5427954A (en) * 1992-04-29 1995-06-27 Shriner's Hospitals For Crippled Children Compositions and methods for detection and treatment of human osteoarthritis

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992013831A1 (en) * 1991-02-07 1992-08-20 British Bio-Technology Limited Hydroxamic acid derivatives, process for their preparation and use thereof
US5427954A (en) * 1992-04-29 1995-06-27 Shriner's Hospitals For Crippled Children Compositions and methods for detection and treatment of human osteoarthritis

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
FOSANG, AMANDA J. ET AL: "Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan", BIOCHEM. J. (1994), 304(2), 347-51 CODEN: BIJOAK;ISSN: 0264-6021, 1994, XP002037746 *
HUGHES, CLARE E. ET AL: "Monoclonal antibodies that specifically recognize neoepitope sequences generated by 'aggrecanase' and matrix metalloproteinase cleavage of aggrecan: application in situ and in vitro", BIOCHEM. J. (1995), 305(3), 799-804 CODEN: BIJOAK;ISSN: 0264-6021, 1995, XP002037744 *
LARK, MICHAEL W. ET AL: "Cell-mediated catabolism of aggrecan. Evidence that cleavage at the "aggrecanase" site (Glu373-Ala374) is a primary event in proteolysis of the interglobular domain", J. BIOL. CHEM. (1995), 270(6), 2550-6 CODEN: JBCHA3;ISSN: 0021-9258, 1995, XP002037745 *
LOHMANDER, L.S. ET AL.: "The structure of aagrecan fragments in human synovial fluid", ARTHRITIS & RHEUMATISM, vol. 36, 1993, pages 1214 - 1222, XP002038145 *
MURPHY G ET AL: "THE N-TERMINAL DOMAIN OF TISSUE INHIBITOR OF METALLOPROTEINASES RETAINS METALLOPROTEINASE INHIBITORY ACTIVITY", BIOCHEMISTRY, vol. 30, no. 33, 20 August 1991 (1991-08-20), pages 8097 - 8102, XP000218096 *

Also Published As

Publication number Publication date
EE9800115A (en) 1998-10-15
CA2237524A1 (en) 1997-05-22
NO982185L (en) 1998-07-13
JP2000502050A (en) 2000-02-22
LV12167A (en) 1998-11-20
PL326714A1 (en) 1998-10-26
CN1202161A (en) 1998-12-16
LV12167B (en) 1999-03-20
HUP0201479A2 (en) 2002-08-28
EP0863885A2 (en) 1998-09-16
MX9803851A (en) 1998-09-30
SI9620120A (en) 1999-06-30
IL124366A0 (en) 1998-12-06
SK63498A3 (en) 1999-01-11
BR9611563A (en) 1999-03-02
WO1997018207A2 (en) 1997-05-22
CZ144798A3 (en) 1998-10-14
HRP960533A2 (en) 1998-04-30
NO982185D0 (en) 1998-05-13

Similar Documents

Publication Publication Date Title
WO1997018207A3 (en) Novel macrocyclic compounds as metalloprotease inhibitors
WO1999009000A3 (en) Novel inhibitors of aggrecanase and matrix metalloproteinases for the treatment of arthritis
UA48939C2 (en) Disubstituted furanons, methods for synthesis, pharmaceutical composition, method for treating inflammatory disease, intermediate substances
WO2000055139A3 (en) Heterocyclic urea and related compounds useful as anti-inflammatory agents
WO2001042231A3 (en) Polyhydroxystilbenes and stilbene oxides as antisoriatic agents and protein kinase inhibitors
PT1465626E (en) Pharmaceutical compositions (kit) comprising dihydropyridinone compounds and an immunoregulatory (or an antiinflammatory) agent and their uses
WO2003053368A3 (en) Chalcone derivatives and their use to treat diseases
WO2003044021A3 (en) Substituted indolizine-like compounds and methods of use
LU91145I9 (en)
WO2002012242A3 (en) Bicyclo-pyrazoles active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
MXPA02010618A (en) Inhibitors of human phosphatidyl-inositol 3-kinase delta.
WO2004062625A3 (en) Macrocyclic beta-secretase inhibitors for treatment of alzheimer's disease
WO2002096361A3 (en) 5-aralkylsulfonyl-3- (pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors
WO2005065195A3 (en) Phenylamide and pyridylamide beta-secretase inhibitors for the treatment of alzheimer's disease
WO2002040702A3 (en) Methods for the treatment of cancer and other diseases and methods of developing the same
WO2005018545A3 (en) Macrocyclic beta-secretase inhibitors for the treatment of alzheimer's disease
CA2234642A1 (en) 3,4-diaryl-2-hydroxy-2,5-dihydrofurans as prodrugs to cox-2 inhibitors
AU7385398A (en) Novel macrocyclic compounds as metalloprotease inhibitors
WO2002007669A3 (en) Phospholipid derivatives of valproic acid and mixtures thereof
DE60008540D1 (en) AROMATIC ESTERS OF CAMPTOTHECINES AND METHOD FOR TREATING CANCER DISEASES
EP1812007A4 (en) Pyridazine compounds and methods
CA2266759A1 (en) 3-mercaptoacetylamino-1,5-substituted-2-oxo-azepan derivatives useful as inhibitors of matrix metalloproteinase
PL328225A1 (en) Diphenylstilbenes as pro-medications used to produce cox-2-inhibitors
DE69715173D1 (en) Bisarylcyclobutenderivate als cyclooxygenasehemmer
WO2001083450A3 (en) (2-oxindol-3-ylidenyl)acetic acid derivatives and their use as protein kinase inhibitors

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 96198327.2

Country of ref document: CN

AK Designated states

Kind code of ref document: A2

Designated state(s): AM AU AZ BR BY CA CN CZ EE HU IL JP KG KR KZ LT LV MD MX NO NZ PL RO RU SG SI SK TJ TM UA VN AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
CFP Corrected version of a pamphlet front page
CR1 Correction of entry in section i

Free format text: PAT.BUL.22/97 UNDER INID (30) "PRIORITY DATA", REPLACE "NOT FURNISHED" BY "08/743439"

121 Ep: the epo has been informed by wipo that ep was designated in this application
WR Later publication of a revised version of an international search report
WWE Wipo information: entry into national phase

Ref document number: 1996943497

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 98-00941

Country of ref document: RO

WWE Wipo information: entry into national phase

Ref document number: 324933

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: PV1998-1447

Country of ref document: CZ

ENP Entry into the national phase

Ref document number: 2237524

Country of ref document: CA

Ref document number: 2237524

Country of ref document: CA

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 1997 519119

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 63498

Country of ref document: SK

Ref document number: 199800372

Country of ref document: EA

WWE Wipo information: entry into national phase

Ref document number: 98-068

Country of ref document: LT

Ref document number: 1019980703618

Country of ref document: KR

Ref document number: PA/a/1998/003851

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 1199800505

Country of ref document: VN

ENP Entry into the national phase

Ref document number: 1998 980104

Country of ref document: LV

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1998980104

Country of ref document: LV

WWP Wipo information: published in national office

Ref document number: 1996943497

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: PV1998-1447

Country of ref document: CZ

WWP Wipo information: published in national office

Ref document number: 98-068

Country of ref document: LT

WWR Wipo information: refused in national office

Ref document number: 98-068

Country of ref document: LT

WWP Wipo information: published in national office

Ref document number: 1019980703618

Country of ref document: KR

WWR Wipo information: refused in national office

Ref document number: PV1998-1447

Country of ref document: CZ

WWW Wipo information: withdrawn in national office

Ref document number: 1019980703618

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1996943497

Country of ref document: EP