CN1205191C - 作为骨吸收抑制剂和玻连蛋白受体拮抗剂的新酰基胍衍生物 - Google Patents

作为骨吸收抑制剂和玻连蛋白受体拮抗剂的新酰基胍衍生物 Download PDF

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Publication number
CN1205191C
CN1205191C CNB988136112A CN98813611A CN1205191C CN 1205191 C CN1205191 C CN 1205191C CN B988136112 A CNB988136112 A CN B988136112A CN 98813611 A CN98813611 A CN 98813611A CN 1205191 C CN1205191 C CN 1205191C
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CN
China
Prior art keywords
alkyl
formula
group
substituted
aryl
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Fee Related
Application number
CNB988136112A
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English (en)
Chinese (zh)
Other versions
CN1284950A (zh
Inventor
A·佩曼
J·克诺勒
G·布雷波尔
K－H·舍伊尼曼
D·卡尼尔托
J－F·古尔弗斯特
T·加德克
R·麦多维尔
S·C·波达赖
R·A·库斯波特森
N·菲尔拉拉
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Aventis Deutschland GmbH
Genentech Inc
Original Assignee
Aventis Pharma Deutschland GmbH
Genentech Inc
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 Aventis Pharma Deutschland GmbH, Genentech Inc filed Critical Aventis Pharma Deutschland GmbH
Publication of CN1284950A publication Critical patent/CN1284950A/zh
Application granted granted Critical
Publication of CN1205191C publication Critical patent/CN1205191C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • 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
    • 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
    • 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
    • C07D239/16—Nitrogen atoms not forming part of a nitro radical acylated on said nitrogen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Indole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CNB988136112A 1997-12-19 1998-12-10 作为骨吸收抑制剂和玻连蛋白受体拮抗剂的新酰基胍衍生物 Expired - Fee Related CN1205191C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP97122520.6 1997-12-19
EP97122520A EP0933367A1 (en) 1997-12-19 1997-12-19 Novel acylguanidine derivates as inhibitors of bone resorption and as vitronectin receptor antagonists

Publications (2)

Publication Number Publication Date
CN1284950A CN1284950A (zh) 2001-02-21
CN1205191C true CN1205191C (zh) 2005-06-08

Family

ID=8227841

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB988136112A Expired - Fee Related CN1205191C (zh) 1997-12-19 1998-12-10 作为骨吸收抑制剂和玻连蛋白受体拮抗剂的新酰基胍衍生物

Country Status (33)

Country Link
US (1) US6492356B1 (https=)
EP (2) EP0933367A1 (https=)
JP (1) JP2001526271A (https=)
KR (1) KR20010033281A (https=)
CN (1) CN1205191C (https=)
AP (1) AP2000001842A0 (https=)
AR (1) AR016437A1 (https=)
AT (1) ATE228112T1 (https=)
AU (1) AU753109B2 (https=)
BG (1) BG64754B1 (https=)
BR (1) BR9814308A (https=)
CA (1) CA2312712A1 (https=)
CU (1) CU23032A3 (https=)
DE (1) DE69809594T2 (https=)
DK (1) DK1042301T3 (https=)
EA (1) EA002921B1 (https=)
ES (1) ES2186251T3 (https=)
HR (1) HRP20000412A2 (https=)
HU (1) HUP0104912A3 (https=)
ID (1) ID26248A (https=)
IL (1) IL136858A0 (https=)
MY (1) MY122269A (https=)
NO (1) NO317420B1 (https=)
NZ (1) NZ504954A (https=)
PL (1) PL341216A1 (https=)
PT (1) PT1042301E (https=)
SI (1) SI1042301T1 (https=)
SK (1) SK9032000A3 (https=)
TR (1) TR200001964T2 (https=)
TW (1) TW446705B (https=)
WO (1) WO1999032457A1 (https=)
YU (1) YU39000A (https=)
ZA (1) ZA9811571B (https=)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6313119B1 (en) 1998-01-23 2001-11-06 Adventis Pharma Deutschland Gmbh Sulfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion
GB9805655D0 (en) 1998-03-16 1998-05-13 Celltech Therapeutics Ltd Chemical compounds
US6521626B1 (en) 1998-03-24 2003-02-18 Celltech R&D Limited Thiocarboxamide derivatives
GB9814414D0 (en) 1998-07-03 1998-09-02 Celltech Therapeutics Ltd Chemical compounds
AU747784B2 (en) * 1998-07-29 2002-05-23 Merck & Co., Inc. Integrin receptor antagonists
GB9821061D0 (en) 1998-09-28 1998-11-18 Celltech Therapeutics Ltd Chemical compounds
GB9826174D0 (en) 1998-11-30 1999-01-20 Celltech Therapeutics Ltd Chemical compounds
EP1028114A1 (en) 1999-02-13 2000-08-16 Aventis Pharma Deutschland GmbH Novel guanidine derivatives as inhibitors of cell adhesion
US6518283B1 (en) 1999-05-28 2003-02-11 Celltech R&D Limited Squaric acid derivatives
EP1065207A1 (en) * 1999-07-02 2001-01-03 Aventis Pharma Deutschland GmbH Naphthyridine derivatives, processes for their preparation, their use, and pharmaceutical compositions comprising them
EP1070707A1 (en) * 1999-07-21 2001-01-24 Aventis Pharma Deutschland GmbH 1,4,5,6-tetrahydropyrimidine derivative as a vitronectin inhibitor
US6534513B1 (en) 1999-09-29 2003-03-18 Celltech R&D Limited Phenylalkanoic acid derivatives
US6849639B2 (en) 1999-12-14 2005-02-01 Amgen Inc. Integrin inhibitors and their methods of use
US6455539B2 (en) 1999-12-23 2002-09-24 Celltech R&D Limited Squaric acid derivates
AU2001248553A1 (en) 2000-04-17 2001-10-30 Celltech R And D Limited Enamine derivatives as cell adhesion molecules
FR2808798A1 (fr) * 2000-05-09 2001-11-16 Hoechst Marion Roussel Inc Nouveaux derives antagonistes du recepteur de la vitronectine
US6403608B1 (en) 2000-05-30 2002-06-11 Celltech R&D, Ltd. 3-Substituted isoquinolin-1-yl derivatives
US6545013B2 (en) 2000-05-30 2003-04-08 Celltech R&D Limited 2,7-naphthyridine derivatives
WO2002004426A1 (en) 2000-07-07 2002-01-17 Celltech R & D Limited Squaric acid derivatives containing a bicyclic heteroaromatic ring as integrin antagonists
EP1176145A1 (en) 2000-07-28 2002-01-30 Aventis Pharma Deutschland GmbH Novel guanidino derivatives as inhibitors of cell adhesion
EP1305291A1 (en) 2000-08-02 2003-05-02 Celltech R&D Limited 3-substituted isoquinolin-1-yl derivatives
EP1197488A1 (en) * 2000-10-10 2002-04-17 Aventis Pharma Deutschland GmbH (2S)-2-(Adamantan-1-ylmethoxycarbonylamino)-3-(4-(2-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)ethyl)benzoylamino)propionic acid isopropyl ester, its preparation and its use
FR2847254B1 (fr) * 2002-11-19 2005-01-28 Aventis Pharma Sa Nouveaux derives antagonistes du recepteur de la vitronectine, leur procede de preparation, leur application comme medicaments et les compositions pharmaceutiques les refermant
FR2870541B1 (fr) 2004-05-18 2006-07-14 Proskelia Sas Derives de pyrimidines antigonistes du recepteur de la vitronectine
UA87854C2 (en) 2004-06-07 2009-08-25 Мерк Энд Ко., Инк. N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
FR2873585B1 (fr) * 2004-07-27 2006-11-17 Aventis Pharma Sa Nouvelles formulations galeniques de principes actifs
US20060039949A1 (en) * 2004-08-20 2006-02-23 Nycz Jeffrey H Acetabular cup with controlled release of an osteoinductive formulation
US20060057184A1 (en) * 2004-09-16 2006-03-16 Nycz Jeffrey H Process to treat avascular necrosis (AVN) with osteoinductive materials
US8414907B2 (en) 2005-04-28 2013-04-09 Warsaw Orthopedic, Inc. Coatings on medical implants to guide soft tissue healing
US9119901B2 (en) * 2005-04-28 2015-09-01 Warsaw Orthopedic, Inc. Surface treatments for promoting selective tissue attachment to medical impants
US20070077267A1 (en) * 2005-10-03 2007-04-05 Sdgi Holdings, Inc. Bioactive composite implants
US20070280986A1 (en) * 2006-06-01 2007-12-06 Carlos Gil Intra-operative coating of implants
US8133553B2 (en) 2007-06-18 2012-03-13 Zimmer, Inc. Process for forming a ceramic layer
US8309521B2 (en) 2007-06-19 2012-11-13 Zimmer, Inc. Spacer with a coating thereon for use with an implant device
US8608049B2 (en) 2007-10-10 2013-12-17 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US20090192609A1 (en) * 2008-01-29 2009-07-30 Zimmer, Inc. Implant device for use in an implant system
SG11201609050UA (en) 2014-05-30 2016-12-29 Pfizer Carbonitrile derivatives as selective androgen receptor modulators
US11020160B2 (en) 2016-03-21 2021-06-01 Warsaw Orthopedic, Inc. Surgical injection system and method
US10709814B2 (en) 2016-04-22 2020-07-14 Warsaw Orthopedic, Inc. Osteoimplant comprising an insoluble fibrous polymer
WO2023275715A1 (en) 2021-06-30 2023-01-05 Pfizer Inc. Metabolites of selective androgen receptor modulators

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US5204350A (en) * 1991-08-09 1993-04-20 Merck & Co., Inc. Method of inhibiting osteoclast-mediated bone resorption by administration of n-heterocyclicalkyl-substituted phenyl derivatives
US5217994A (en) * 1991-08-09 1993-06-08 Merck & Co., Inc. Method of inhibiting osteoclast-mediated bone resorption by administration of aminoalkyl-substituted phenyl derivatives
AU674553B2 (en) * 1992-10-14 1997-01-02 Merck & Co., Inc. Fibrinogen receptor antagonists
JPH08504194A (ja) * 1992-12-01 1996-05-07 メルク エンド カンパニー インコーポレーテッド フィブリノーゲンレセプターアンタゴニスト
JP3895792B2 (ja) * 1995-12-08 2007-03-22 プロスケリア・エス・ア・エス 骨形成促進剤

Also Published As

Publication number Publication date
TR200001964T2 (tr) 2000-11-21
ZA9811571B (en) 1999-06-21
DE69809594D1 (de) 2003-01-02
AU2270099A (en) 1999-07-12
TW446705B (en) 2001-07-21
HUP0104912A3 (en) 2002-09-30
CN1284950A (zh) 2001-02-21
JP2001526271A (ja) 2001-12-18
HRP20000412A2 (en) 2000-10-31
PT1042301E (pt) 2003-04-30
KR20010033281A (ko) 2001-04-25
PL341216A1 (en) 2001-03-26
BG104544A (en) 2001-03-30
EA200000682A1 (ru) 2000-12-25
HK1034974A1 (en) 2001-11-09
DK1042301T3 (da) 2003-03-17
ID26248A (id) 2000-12-07
ES2186251T3 (es) 2003-05-01
NO20003118L (no) 2000-08-21
SK9032000A3 (en) 2001-04-09
AP2000001842A0 (en) 2000-06-30
EA002921B1 (ru) 2002-10-31
AU753109B2 (en) 2002-10-10
CU23032A3 (es) 2005-03-22
EP1042301B1 (en) 2002-11-20
EP1042301A1 (en) 2000-10-11
ATE228112T1 (de) 2002-12-15
NO20003118D0 (no) 2000-06-16
US6492356B1 (en) 2002-12-10
HUP0104912A1 (hu) 2002-07-29
MY122269A (en) 2006-03-31
NZ504954A (en) 2002-05-31
BG64754B1 (bg) 2006-02-28
IL136858A0 (en) 2001-06-14
BR9814308A (pt) 2000-10-10
WO1999032457A1 (en) 1999-07-01
AR016437A1 (es) 2001-07-04
SI1042301T1 (en) 2003-04-30
NO317420B1 (no) 2004-10-25
EP0933367A1 (en) 1999-08-04
CA2312712A1 (en) 1999-07-01
DE69809594T2 (de) 2003-04-24
YU39000A (sh) 2002-11-15

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