OA11076A - Vitronectin receptor antagonists - Google Patents

Vitronectin receptor antagonists Download PDF

Info

Publication number: OA11076A
Authority: OA; OAPI
Prior art keywords: compound; dibenzo; dihydro; cycloheptene; cells
Prior art date: 1997-01-08

Application number

OA9900155A

Other languages

English (en)

Inventor

William H Miller

William E Bondinell

Thomas Wen Fu Ku

Original Assignee

Smithline Beecham Corp

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.)

1997-01-08

Filing date

1999-07-08

Publication date

2003-03-13

1999-07-08 Application filed by Smithline Beecham Corp filed Critical Smithline Beecham Corp

2003-03-13 Publication of OA11076A publication Critical patent/OA11076A/en

Links

102100022337 Integrin alpha-V Human genes 0.000 title description 17
108010048673 Vitronectin Receptors Proteins 0.000 title description 17
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239000013641 positive control Substances 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
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239000000047 product Substances 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000007634 remodeling Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
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238000013391 scatchard analysis Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
230000015590 smooth muscle cell migration Effects 0.000 description 1
239000003998 snake venom Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
229960001790 sodium citrate Drugs 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 1
239000001433 sodium tartrate Substances 0.000 description 1
229960002167 sodium tartrate Drugs 0.000 description 1
235000011004 sodium tartrates Nutrition 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
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239000008117 stearic acid Substances 0.000 description 1
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239000011550 stock solution Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 1
BXVLZVTWCPCGHV-UHFFFAOYSA-N tert-butyl 6-oxo-5,11-dihydrodibenzo[3,2-e:2',1'-f][7]annulene-3-carboxylate Chemical compound O=C1CC2=CC(C(=O)OC(C)(C)C)=CC=C2CC2=CC=CC=C21 BXVLZVTWCPCGHV-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229940034208 thyroxine Drugs 0.000 description 1
XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
229950003937 tolonium Drugs 0.000 description 1
HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
238000001890 transfection Methods 0.000 description 1
108091007466 transmembrane glycoproteins Proteins 0.000 description 1
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YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
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238000010626 work up procedure Methods 0.000 description 1
230000029663 wound healing Effects 0.000 description 1

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
- 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
- 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
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (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)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Rheumatology (AREA)
Physical Education & Sports Medicine (AREA)
Engineering & Computer Science (AREA)
Orthopedic Medicine & Surgery (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

OA9900155A 1997-01-08 1999-07-08 Vitronectin receptor antagonists OA11076A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US3402697P	1997-01-08	1997-01-08

Publications (1)

Publication Number	Publication Date
OA11076A true OA11076A (en)	2003-03-13

Family

ID=21873846

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9900155A OA11076A (en)	1997-01-08	1999-07-08	Vitronectin receptor antagonists

Country Status (30)

Country	Link
US (2)	US6069158A (de)
EP (1)	EP0977735B1 (de)
JP (1)	JP2001508067A (de)
KR (1)	KR20000069941A (de)
CN (1)	CN1249745A (de)
AP (1)	AP9901597A0 (de)
AR (1)	AR010873A1 (de)
AT (1)	ATE235467T1 (de)
AU (1)	AU729641B2 (de)
BG (1)	BG103548A (de)
BR (1)	BR9806852A (de)
CA (1)	CA2276738A1 (de)
CO (1)	CO4920232A1 (de)
DE (1)	DE69812602T2 (de)
DZ (1)	DZ2395A1 (de)
EA (1)	EA199900630A1 (de)
ES (1)	ES2196534T3 (de)
HU (1)	HUP0001945A3 (de)
ID (1)	ID23168A (de)
IL (1)	IL130760A0 (de)
MA (1)	MA26462A1 (de)
NO (1)	NO993350L (de)
NZ (1)	NZ336560A (de)
OA (1)	OA11076A (de)
PE (1)	PE44799A1 (de)
PL (1)	PL334499A1 (de)
SK (1)	SK92799A3 (de)
TR (1)	TR199901575T2 (de)
WO (1)	WO1998030542A1 (de)
ZA (1)	ZA9896B (de)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2001514253A (ja) *	1997-09-04	2001-09-11	スミスクライン・ビーチャム・コーポレイション	インテグリンレセプターアンタゴニスト
AR015446A1 (es) *	1997-09-19	2001-05-02	Smithkline Beecham Corp	Antagonistas de receptores de vitronectina, composicion farmaceutica que los contiene, procedimiento para su preparacion, su uso para la elaboracion de unmedicamento y compuestos intermediarios
US6576643B2 (en)	1997-09-19	2003-06-10	Smithkline Beecham Corporation	Vitronectin receptor antagonists
CN1140511C (zh)	1998-04-09	2004-03-03	明治制果株式会社	作为整合素αvβ3拮抗剂的氨基哌啶衍生物
JP4240424B2 (ja) *	1998-10-23	2009-03-18	エルジーディスプレイカンパニーリミテッド	エッチング剤及びこれを用いた電子機器用基板の製造方法
US6339083B1 (en)	1998-12-14	2002-01-15	Bayer Aktiengesellschaft	Multiheterocyclic pharmAceuticals
AU747503B2 (en)	1999-02-03	2002-05-16	Merck & Co., Inc.	Benzazepine derivatives as alpha-V integrin receptor antagonists
DE19916837A1 (de) *	1999-04-14	2000-10-19	Merck Patent Gmbh	Dibenzoazulenderivate
WO2001010844A1 (fr)	1999-08-05	2001-02-15	Meiji Seika Kaisha, Ltd.	DERIVES D'ACIDE φ-AMINO-α-HYDROXYCARBOXYLIQUE POSSEDANT UN ANTAGONISME αvβ3 D'INTEGRINE
DE19936780A1 (de)	1999-08-09	2001-02-15	Basf Ag	Neue Antagonisten von Integrinrezeptoren
FR2806082B1 (fr) *	2000-03-07	2002-05-17	Adir	Nouveaux composes bicycliques antagonistes des recepteurs de la vitronectine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
DE60118025T2 (de)	2000-10-24	2006-11-23	Merck & Co., Inc.	Dibenzoxazepin-alpha-v-integrin-rezeptorantagonist
JP4660067B2 (ja)	2001-04-24	2011-03-30	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	抗血管新生剤とＴＮＦαとを用いる組合せ療法
EP1443963B1 (de)	2001-10-22	2014-05-21	The Scripps Research Institute	Antikörper-targeting-verbindungen
GB0215867D0 (en) *	2002-07-09	2002-08-14	Glaxosmithkline Spa	Novel method and compounds
AU2012216372B2 (en) *	2004-04-02	2015-01-22	The Regents Of The University Of California	Methods and compositions for treating and preventing disease associated with alphaVbeta5 integrin
AU2005229015C1 (en) *	2004-04-02	2013-01-17	The Regents Of The University Of California	Methods and compositions for treating and preventing disease associated with alphaVbeta5 integrin
UA87854C2 (en)	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
US8282943B2 (en)	2005-05-31	2012-10-09	Ralf Jochem	Therapeutic composition for use in the prevention and treatment of bone metastases
US20070122408A1 (en) *	2005-10-20	2007-05-31	The Scripps Research Institute	Fc Labeling for Immunostaining and Immunotargeting
BRPI0706540A2 (pt)	2006-01-18	2011-03-29	Merck Patent Gmbh	terapia especìfica usando ligantes de integrina para tratar cáncer
EP2441464B1 (de)	2007-01-18	2014-04-09	Merck Patent GmbH	Integrin-liganden zur verwendung in der behandlung von darmkrebs
EP2222636B1 (de)	2007-12-21	2013-04-10	Ligand Pharmaceuticals Inc.	Selektive androgenrezeptormodulatoren (sarms) und ihre verwendung
JP2012517447A (ja)	2009-02-10	2012-08-02	ザスクリプスリサーチインスティチュート	化学的にプログラムされたワクチン接種法
CN102448497A (zh)	2009-05-25	2012-05-09	默克专利有限公司	在癌症治疗中的西仑吉肽的持续给药
EP2456460A4 (de)	2009-07-24	2013-02-20	Univ California	Verfahren und zusammensetzungen zur behandlung und prävention von mit avb5-integrin assoziierten krankheiten
ES2864079T3 (es)	2014-05-30	2021-10-13	Pfizer	Derivados de carbonitrilo como moduladores selectivos del receptor de andrógenos
WO2020214834A1 (en)	2019-04-19	2020-10-22	Ligand Pharmaceuticals Inc.	Crystalline forms and methods of producing crystalline forms of a compound
WO2023275715A1 (en)	2021-06-30	2023-01-05	Pfizer Inc.	Metabolites of selective androgen receptor modulators

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE794424A (fr) *	1972-01-24	1973-07-23	Science Union & Cie	Nouveaux dibenzocycloheptenes, leur procede d'obtention et leur application comme medicament
US3906032A (en) *	1972-11-10	1975-09-16	Squibb & Sons Inc	Dihydroxy-tetrahydronaphthyoxyisobutyric acids and alkyl esters and salts thereof
IT1222986B (it) *	1987-10-23	1990-09-12	Texcontor Ets	Derivati dell'efedrina esterificata aventi attivita' antiulcera prolungata nel tempo
AU612437B2 (en) *	1987-12-14	1991-07-11	Kyowa Hakko Kogyo Co. Ltd.	Tricyclic compounds
WO1997001540A1 (en) *	1995-06-29	1997-01-16	Smithkline Beecham Corporation	Integrin receptor antagonists
CZ203898A3 (cs) *	1995-12-29	1999-03-17	Smithkline Beecham Corporation	Antagonista vitronektinového receptoru, farmaceutický přípravek s jeho obsahem, způsob a použití
EP1000031A4 (de) *	1997-07-25	2001-08-16	Smithkline Beecham Corp	Vitronectinrezeptor-antagonist
AR015446A1 (es) *	1997-09-19	2001-05-02	Smithkline Beecham Corp	Antagonistas de receptores de vitronectina, composicion farmaceutica que los contiene, procedimiento para su preparacion, su uso para la elaboracion de unmedicamento y compuestos intermediarios

1997
- 1997-12-30 CO CO97075531A patent/CO4920232A1/es unknown
1998
- 1998-01-02 MA MA24917A patent/MA26462A1/fr unknown
- 1998-01-05 AR ARP980100031A patent/AR010873A1/es not_active Application Discontinuation
- 1998-01-07 ZA ZA9896A patent/ZA9896B/xx unknown
- 1998-01-07 PE PE1998000013A patent/PE44799A1/es not_active Application Discontinuation
- 1998-01-08 JP JP53117598A patent/JP2001508067A/ja active Pending
- 1998-01-08 TR TR1999/01575T patent/TR199901575T2/xx unknown
- 1998-01-08 EP EP98902477A patent/EP0977735B1/de not_active Expired - Lifetime
- 1998-01-08 PL PL98334499A patent/PL334499A1/xx unknown
- 1998-01-08 SK SK927-99A patent/SK92799A3/sk unknown
- 1998-01-08 AP APAP/P/1999/001597A patent/AP9901597A0/en unknown
- 1998-01-08 HU HU0001945A patent/HUP0001945A3/hu unknown
- 1998-01-08 AU AU59127/98A patent/AU729641B2/en not_active Ceased
- 1998-01-08 EA EA199900630A patent/EA199900630A1/ru unknown
- 1998-01-08 BR BR9806852-0A patent/BR9806852A/pt not_active Application Discontinuation
- 1998-01-08 ES ES98902477T patent/ES2196534T3/es not_active Expired - Lifetime
- 1998-01-08 KR KR1019997006154A patent/KR20000069941A/ko not_active Ceased
- 1998-01-08 CA CA002276738A patent/CA2276738A1/en not_active Abandoned
- 1998-01-08 CN CN98802983A patent/CN1249745A/zh active Pending
- 1998-01-08 IL IL13076098A patent/IL130760A0/xx unknown
- 1998-01-08 AT AT98902477T patent/ATE235467T1/de not_active IP Right Cessation
- 1998-01-08 US US09/331,914 patent/US6069158A/en not_active Expired - Lifetime
- 1998-01-08 WO PCT/US1998/000490 patent/WO1998030542A1/en not_active Ceased
- 1998-01-08 DE DE69812602T patent/DE69812602T2/de not_active Expired - Lifetime
- 1998-01-08 NZ NZ336560A patent/NZ336560A/xx unknown
- 1998-01-08 ID IDW990650D patent/ID23168A/id unknown
- 1998-06-07 DZ DZ980005A patent/DZ2395A1/xx active
1999
- 1999-07-01 BG BG103548A patent/BG103548A/xx unknown
- 1999-07-07 NO NO993350A patent/NO993350L/no not_active Application Discontinuation
- 1999-07-08 OA OA9900155A patent/OA11076A/en unknown
2000
- 2000-04-18 US US09/551,743 patent/US6191304B1/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
BG103548A (en)	2000-11-30
AR010873A1 (es)	2000-07-12
BR9806852A (pt)	2001-08-07
DZ2395A1 (fr)	2003-06-04
CN1249745A (zh)	2000-04-05
AU5912798A (en)	1998-08-03
CA2276738A1 (en)	1998-07-16
TR199901575T2 (xx)	1999-11-22
DE69812602D1 (de)	2003-04-30
HUP0001945A2 (hu)	2000-10-28
IL130760A0 (en)	2001-01-28
KR20000069941A (ko)	2000-11-25
NZ336560A (en)	2000-11-24
NO993350L (no)	1999-09-06
WO1998030542A1 (en)	1998-07-16
EP0977735B1 (de)	2003-03-26
PL334499A1 (en)	2000-02-28
AU729641B2 (en)	2001-02-08
AP9901597A0 (en)	1999-09-30
ZA9896B (en)	1998-10-14
PE44799A1 (es)	1999-06-10
ID23168A (id)	2000-03-23
CO4920232A1 (es)	2000-05-29
DE69812602T2 (de)	2004-02-19
MA26462A1 (fr)	2004-12-20
HUP0001945A3 (en)	2001-12-28
ATE235467T1 (de)	2003-04-15
ES2196534T3 (es)	2003-12-16
US6191304B1 (en)	2001-02-20
EP0977735A4 (de)	2000-04-05
JP2001508067A (ja)	2001-06-19
EP0977735A1 (de)	2000-02-09
SK92799A3 (en)	1999-12-10
NO993350D0 (no)	1999-07-07
US6069158A (en)	2000-05-30
EA199900630A1 (ru)	2000-02-28

Publication	Publication Date	Title
OA11076A (en)	2003-03-13	Vitronectin receptor antagonists
AU733417B2 (en)	2001-05-17	Vitronectin receptor antagonists
JP2000502708A (ja)	2000-03-07	ビトロネクチン受容体拮抗物質
HU226056B1 (en)	2008-04-28	Acetic acid derivatives with dibenzo[a,d]cycloheptene and dibenz[b,e]azepine skeleton, process for their preparation and pharmaceutical compositions containing them
WO1999005107A1 (en)	1999-02-04	Vitronectin receptor antagonist
AU738433B2 (en)	2001-09-20	Vitronectin receptor antagonists
CA2304000A1 (en)	1999-04-01	Vitronectin receptor antagonist
EP1146874B1 (de)	2004-09-22	Vitronectin rezeptor antagonist
US20020019387A1 (en)	2002-02-14	Vitronectin receptor antagonist
CZ241599A3 (cs)	2000-01-12	Antagonista vitronektinového receptorů
US6576643B2 (en)	2003-06-10	Vitronectin receptor antagonists
CZ2000979A3 (cs)	2000-11-15	Antagonista vitronektinového receptoru
MXPA01005547A (en)	2001-12-04	Vitronectin receptor antagonist