BG104314A - Vitronectin receptor antagonists - Google Patents

Vitronectin receptor antagonists

Info

Publication number
BG104314A
BG104314A BG104314A BG10431400A BG104314A BG 104314 A BG104314 A BG 104314A BG 104314 A BG104314 A BG 104314A BG 10431400 A BG10431400 A BG 10431400A BG 104314 A BG104314 A BG 104314A
Authority
BG
Bulgaria
Prior art keywords
receptor antagonists
vitronectin receptor
6alkyl
halo
alkyl
Prior art date
Application number
BG104314A
Other languages
Bulgarian (bg)
Inventor
William E. Bondinell
William H. Miller
Dirk Heerding
James M. Samanen
Original Assignee
Smithkline Beecham Corporation
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 Corporation filed Critical Smithkline Beecham Corporation
Publication of BG104314A publication Critical patent/BG104314A/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
    • C07D213/73—Unsubstituted amino or imino radicals
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P35/00—Antineoplastic agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • 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
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings 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
    • C07D233/44—Nitrogen atoms not forming part of a nitro radical
    • C07D233/48—Nitrogen atoms not forming part of a nitro radical with acyclic hydrocarbon or substituted acyclic hydrocarbon radicals, attached to said nitrogen atoms
    • 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
    • C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
    • C07D239/12—Nitrogen atoms not forming part of a nitro radical
    • C07D239/14—Nitrogen atoms not forming part of a nitro radical with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to said nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles 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 in position 2
    • 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
    • C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
    • C07D313/02—Seven-membered rings
    • C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
    • C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
    • C07D313/14—[b,f]-condensed
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Compounds of formula are disclosed which are vitronectin receptor antagonists and are useful in the treatment of osteoporosis wherein: A is CH2 or O; R1 is H, halo or C1-6alkyl; R2 is H, C1-6alkyl or CH2NR"R"; X is O or CH2; Y is G is NR", S or O, R' is H, C1-6 alkyl, OC1-6 alkyl, SC1-6alkyl, NR"R" or halo; each R" independently is H or C1-6alkyl; and s is O, 1 or 2; or a pharmaceutical acceptable salt thereof. 38 claims
BG104314A 1997-09-19 2000-04-07 Vitronectin receptor antagonists BG104314A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US5934297P 1997-09-19 1997-09-19
US6343897P 1997-10-29 1997-10-29
PCT/US1998/019466 WO1999015508A1 (en) 1997-09-19 1998-09-18 Vitronectin receptor antagonists

Publications (1)

Publication Number Publication Date
BG104314A true BG104314A (en) 2001-01-31

Family

ID=26738652

Family Applications (1)

Application Number Title Priority Date Filing Date
BG104314A BG104314A (en) 1997-09-19 2000-04-07 Vitronectin receptor antagonists

Country Status (26)

Country Link
EP (1) EP1025090A4 (en)
JP (1) JP2001517658A (en)
KR (1) KR20010024141A (en)
CN (1) CN1278250A (en)
AP (1) AP2000001766A0 (en)
AR (1) AR015446A1 (en)
AU (1) AU738433B2 (en)
BG (1) BG104314A (en)
BR (1) BR9812340A (en)
CA (1) CA2303487A1 (en)
CO (1) CO5011087A1 (en)
DZ (1) DZ2609A1 (en)
EA (1) EA200000336A1 (en)
HU (1) HUP0003641A3 (en)
ID (1) ID24162A (en)
IL (1) IL135028A0 (en)
MA (1) MA26547A1 (en)
NO (1) NO20001407D0 (en)
NZ (1) NZ503389A (en)
OA (1) OA11341A (en)
PE (1) PE122699A1 (en)
PL (1) PL339381A1 (en)
SK (1) SK4082000A3 (en)
TR (1) TR200000721T2 (en)
TW (1) TW513303B (en)
WO (1) WO1999015508A1 (en)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CO4920232A1 (en) * 1997-01-08 2000-05-29 Smithkline Beecham Corp DIBENZO [A, D] CYCLLOHEPTANE ACETIC ACIDS WITH VITRONECTIN RECEPTOR ANTAGONIST ACTIVITY
AU747503B2 (en) 1999-02-03 2002-05-16 Merck & Co., Inc. Benzazepine derivatives as alpha-V integrin receptor antagonists
DE19936780A1 (en) 1999-08-09 2001-02-15 Basf Ag New integrin receptor antagonists
EG24179A (en) * 1999-09-07 2008-09-28 Smithkline Beecham Corp Vitronectin receptor antagonists
US6881736B1 (en) 1999-09-07 2005-04-19 Smithkline Beecham Corporation Vitronectin receptor antagonists
US6514964B1 (en) 1999-09-27 2003-02-04 Amgen Inc. Fused cycloheptane and fused azacycloheptane compounds and their methods of use
FR2806082B1 (en) * 2000-03-07 2002-05-17 Adir NOVEL BICYCLIC ANTAGONIST VITRONECTIN RECEPTOR COMPOUNDS, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
WO2001096310A1 (en) * 2000-06-15 2001-12-20 Pharmacia Corporation Dihydrostilbene alkanoic acid derivatives useful as vitronectin antagonists
DE60118025T2 (en) * 2000-10-24 2006-11-23 Merck & Co., Inc. Dibenzoxazepine ALPHA-V integrin receptor ANTAGONIST
AU2002316855B2 (en) 2001-04-24 2008-03-13 Merck Patent Gmbh Combination therapy using anti-angiogenic agents and TNFalpha
GB0215867D0 (en) * 2002-07-09 2002-08-14 Glaxosmithkline Spa Novel method and compounds
US20040224986A1 (en) 2002-08-16 2004-11-11 Bart De Corte Piperidinyl targeting compounds that selectively bind integrins
UA87854C2 (en) 2004-06-07 2009-08-25 Мерк Энд Ко., Инк. N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
ES2425396T3 (en) 2006-01-18 2013-10-15 Merck Patent Gmbh Specific therapy using integrin ligands for cancer treatment
DK2101805T3 (en) 2007-01-18 2013-01-21 Merck Patent Gmbh INTEGRIC LANDS FOR USE IN CANCER TREATMENT
JP2012528079A (en) 2009-05-25 2012-11-12 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング Continuous administration of integrin ligand to treat cancer
US10328082B2 (en) 2014-05-30 2019-06-25 Pfizer Inc. Methods of use and combinations
WO2023275715A1 (en) 2021-06-30 2023-01-05 Pfizer Inc. Metabolites of selective androgen receptor modulators

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH450398A (en) * 1964-02-18 1968-01-31 Hoffmann La Roche Process for the preparation of dibenzocycloheptatriene compounds
US3335148A (en) * 1966-02-17 1967-08-08 Lilly Co Eli 9(3-pyridyl)derivative of fluorene, 9-fluorenol, xanthene, 9-xanthenol and the corresponding nonphytotoxic acid addition salts thereof
US5698551A (en) * 1995-04-07 1997-12-16 Novo Nordisk A/S Heterocyclic compounds
DE69627899T2 (en) * 1995-06-29 2004-05-19 Smithkline Beecham Corp. Integrin receptor Antagonist
US5659033A (en) * 1995-09-13 1997-08-19 Neurogen Corporation N-aminoalkylfluorenecarboxamides; a new class of dopamine receptor subtype specific ligands
JP2001501951A (en) * 1996-10-07 2001-02-13 スミスクライン・ビーチャム・コーポレイション How to stimulate bone formation
CO4920232A1 (en) * 1997-01-08 2000-05-29 Smithkline Beecham Corp DIBENZO [A, D] CYCLLOHEPTANE ACETIC ACIDS WITH VITRONECTIN RECEPTOR ANTAGONIST ACTIVITY

Also Published As

Publication number Publication date
EA200000336A1 (en) 2000-10-30
NO20001407L (en) 2000-03-17
TW513303B (en) 2002-12-11
CO5011087A1 (en) 2001-02-28
PE122699A1 (en) 2000-02-12
CN1278250A (en) 2000-12-27
WO1999015508A1 (en) 1999-04-01
KR20010024141A (en) 2001-03-26
NO20001407D0 (en) 2000-03-17
OA11341A (en) 2003-12-10
CA2303487A1 (en) 1999-04-01
ID24162A (en) 2000-07-13
PL339381A1 (en) 2000-12-18
IL135028A0 (en) 2001-05-20
DZ2609A1 (en) 2003-03-01
AR015446A1 (en) 2001-05-02
AU738433B2 (en) 2001-09-20
AP2000001766A0 (en) 1998-09-18
AU9397298A (en) 1999-04-12
MA26547A1 (en) 2004-12-20
HUP0003641A2 (en) 2001-03-28
EP1025090A1 (en) 2000-08-09
NZ503389A (en) 2002-03-28
HUP0003641A3 (en) 2002-10-28
TR200000721T2 (en) 2000-11-21
BR9812340A (en) 2001-12-18
EP1025090A4 (en) 2000-11-08
SK4082000A3 (en) 2000-09-12
JP2001517658A (en) 2001-10-09

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