HRP20010206A2 - NON-PEPTIDE GnRH AGENTS, METHODS AND INTERMEDIATES FOR THEIR PREPARATION - Google Patents
NON-PEPTIDE GnRH AGENTS, METHODS AND INTERMEDIATES FOR THEIR PREPARATION Download PDFInfo
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- HRP20010206A2 HRP20010206A2 HR20010206A HRP20010206A HRP20010206A2 HR P20010206 A2 HRP20010206 A2 HR P20010206A2 HR 20010206 A HR20010206 A HR 20010206A HR P20010206 A HRP20010206 A HR P20010206A HR P20010206 A2 HRP20010206 A2 HR P20010206A2
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- unsubstituted alkyl
- aryl
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Classifications
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- 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
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P5/04—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin for decreasing, blocking or antagonising the activity of the hypothalamic hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/14—Radicals substituted by 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
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
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- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having 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
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- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom 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
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- 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
- C07D405/14—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 three or more hetero rings
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- 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
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- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US9752098P | 1998-08-20 | 1998-08-20 | |
PCT/US1999/018790 WO2000020358A2 (en) | 1998-08-20 | 1999-08-20 | NON-PEPTIDE GnRH AGENTS, METHODS AND INTERMEDIATES FOR THEIR PREPARATION |
Publications (1)
Publication Number | Publication Date |
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HRP20010206A2 true HRP20010206A2 (en) | 2004-02-29 |
Family
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Family Applications (1)
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HR20010206A HRP20010206A2 (en) | 1998-08-20 | 2001-03-20 | NON-PEPTIDE GnRH AGENTS, METHODS AND INTERMEDIATES FOR THEIR PREPARATION |
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JP (1) | JP2002535244A (zh) |
KR (1) | KR20010085402A (zh) |
CN (1) | CN1379666A (zh) |
AP (1) | AP2001002053A0 (zh) |
AT (1) | ATE291423T1 (zh) |
AU (1) | AU759310B2 (zh) |
BG (1) | BG105362A (zh) |
BR (1) | BR9913374A (zh) |
CA (1) | CA2341346A1 (zh) |
CZ (1) | CZ2001523A3 (zh) |
DE (1) | DE69924387D1 (zh) |
EA (1) | EA200100255A1 (zh) |
EE (1) | EE200100102A (zh) |
ES (1) | ES2237966T3 (zh) |
GE (1) | GEP20043315B (zh) |
HR (1) | HRP20010206A2 (zh) |
HU (1) | HUP0103622A3 (zh) |
ID (1) | ID29244A (zh) |
IL (1) | IL141396A0 (zh) |
IS (1) | IS5846A (zh) |
LT (1) | LT4904B (zh) |
LV (1) | LV12732B (zh) |
NO (1) | NO20010309L (zh) |
NZ (1) | NZ509252A (zh) |
OA (1) | OA11599A (zh) |
PL (1) | PL356984A1 (zh) |
SI (1) | SI20746A (zh) |
SK (1) | SK2262001A3 (zh) |
TR (1) | TR200100631T2 (zh) |
WO (1) | WO2000020358A2 (zh) |
YU (1) | YU13701A (zh) |
ZA (1) | ZA200100831B (zh) |
Families Citing this family (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2133587C (en) * | 1992-04-22 | 2008-11-18 | Marcus F. Boehm | Compounds having selectivity for retinoid x receptors |
IL145401A0 (en) * | 1999-03-24 | 2002-06-30 | Anormed Inc | Chemokine receptor binding heterocyclic compounds |
CO5370679A1 (es) * | 1999-06-01 | 2004-02-27 | Smithkline Beecham Corp | Inhibidores fab 1 |
TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
BR0210191A (pt) * | 2001-06-06 | 2004-04-06 | Agouron Pharma | Agentes não peptìdicos da gnrh, composições farmacêuticas e métodos para o seu uso, e processos para os preparar e aos seus intermediários |
JP4544857B2 (ja) * | 2001-06-11 | 2010-09-15 | ヴァイロケム ファーマ インコーポレイテッド | Flavivirus感染の治療または予防のための化合物および方法 |
CA2458533C (en) | 2001-10-09 | 2011-01-04 | Tularik Inc. | Imidazole derivates as anti-inflammatory agents |
GB0126292D0 (en) * | 2001-11-01 | 2002-01-02 | Smithkline Beecham Plc | Compounds |
JP2005170790A (ja) * | 2002-01-09 | 2005-06-30 | Ajinomoto Co Inc | N−アルキルスルフォニル置換アミド誘導体 |
US6521395B1 (en) * | 2002-01-30 | 2003-02-18 | Eastman Kodak Company | Infrared couplers for incorporating and recovering metadata |
AU2003202115A1 (en) * | 2002-02-12 | 2003-09-04 | Pfizer Inc. | Non-peptide compounds affecting the action of gonadotropin-releasing hormone (gnrh) |
TW200304820A (en) * | 2002-03-25 | 2003-10-16 | Avanir Pharmaceuticals | Use of benzimidazole analogs in the treatment of cell proliferation |
BR0312123A (pt) | 2002-06-13 | 2005-03-29 | Pfizer | Agentes de gnrh não peptìdicos, composições farmacêuticas e métodos para o seu uso |
ATE334687T1 (de) * | 2002-11-20 | 2006-08-15 | Paradigm Therapeutics Ltd | Heterozyklische siliziumverbindungen und deren verwendung zur behandlung von krankheiten oder zuständen, die mit gonadotropin-freisetzenden hormon assoziiert sind |
CN100451004C (zh) * | 2003-03-31 | 2009-01-14 | 大正制药株式会社 | 嘧啶衍生物 |
EP1464335A3 (en) * | 2003-03-31 | 2007-05-09 | Taisho Pharmaceutical Co. Ltd. | Quinoline, tetrahydroquinoline and pyrimidine derivatives as mch antagonist |
US7427683B2 (en) * | 2003-04-25 | 2008-09-23 | Ortho-Mcneil Pharmaceutical, Inc. | c-fms kinase inhibitors |
EP1631560A2 (en) * | 2003-04-25 | 2006-03-08 | 3-Dimensional Pharmaceuticals, Inc. | C-fms kinase inhibitors |
EP1628661A2 (en) * | 2003-06-05 | 2006-03-01 | Vertex Pharmaceuticals Incorporated | Modulators of vr1 receptor |
JP2007516192A (ja) * | 2003-07-09 | 2007-06-21 | パラダイム・セラピューティクス・リミテッド | 有機ケイ素化合物およびその使用 |
RU2303595C2 (ru) | 2003-07-10 | 2007-07-27 | Пэредайм Терапьютикс Лтд. | Силиконовые соединения и их применение (варианты) |
US20050182061A1 (en) * | 2003-10-02 | 2005-08-18 | Jeremy Green | Phthalimide compounds useful as protein kinase inhibitors |
US20090291915A1 (en) * | 2004-12-17 | 2009-11-26 | Graham Andrew Showell | Silicon Compounds and Their Use |
KR20080016597A (ko) | 2005-05-13 | 2008-02-21 | 바이로켐 파마 인코포레이티드 | 플라비바이러스 감염의 예방 또는 치료용 화합물 및 그의예방 또는 치료 방법 |
US8193206B2 (en) | 2005-06-14 | 2012-06-05 | Taigen Biotechnology Co., Ltd. | Pyrimidine compounds |
EP1890703B1 (en) | 2005-06-14 | 2016-05-11 | Taigen Biotechnology | Pyrimidine compounds as chemokine receptors inhibitors |
JP2008543965A (ja) * | 2005-06-28 | 2008-12-04 | タケダ・ケンブリッジ・リミテッド | 複素環式非ペプチドgnrh拮抗薬 |
DK1910384T3 (da) * | 2005-08-04 | 2012-12-17 | Sirtris Pharmaceuticals Inc | Imidazo [2,1-b] thiazol-derivater som sirtuinmodulerende forbindelser |
EP2001480A4 (en) | 2006-03-31 | 2011-06-15 | Abbott Lab | Indazole CONNECTIONS |
US20080070987A1 (en) * | 2006-05-12 | 2008-03-20 | Francesc Yraola Font | Meta-xylylenediamine vanadate salts |
CL2008001822A1 (es) | 2007-06-20 | 2009-03-13 | Sirtris Pharmaceuticals Inc | Compuestos derivados de tiazolo[5,4-b]piridina; composicion farmaceutica que comprende a dichos compuestos; y uso del compuesto en el tratamiento de la resistencia a la insulina, sindrome metabolico, diabetes, entre otras. |
CA2701946A1 (en) * | 2007-10-11 | 2009-04-16 | Vertex Pharmaceuticals Incorporated | Heteroaryl amides useful as inhibitors of voltage-gated sodium channels |
AU2007360907A1 (en) | 2007-10-31 | 2009-05-07 | Research Foundation Itsuu Laboratory | Retinoid prodrug compound |
US8372849B2 (en) | 2008-04-21 | 2013-02-12 | Taigen Biotechnology Co., Ltd. | Heterocyclic compounds |
UY31984A (es) * | 2008-07-16 | 2010-02-26 | Boehringer Ingelheim Int | DERIVADOS DE 1-(3,4-difluorobencil)-6-oxo-1,6-dihidropirimidin-5-carboxamidas N-sustituidas y de 2-(3,4-difluorobencil)-3-oxo-2,3-dihidro-1H-pirazol-4-carboxamidas N-sustituidas. |
WO2010056847A2 (en) | 2008-11-13 | 2010-05-20 | Taigen Biotechnology Co., Ltd. | Lyophilization formulation |
RU2013109143A (ru) | 2010-08-05 | 2014-09-10 | Амджен Инк. | Бензимидазол- и азабензимидазолсодержащие соединения, которые ингибируют киназу анапластической лимфомы |
CN102050823A (zh) * | 2010-10-27 | 2011-05-11 | 华东理工大学 | 新型光稳定剂-鸟嘌呤类似物的合成及表征 |
US9199918B2 (en) * | 2011-02-15 | 2015-12-01 | Georgetown University | Small molecule inhibitors of AGBL2 |
WO2012155199A1 (en) | 2011-05-16 | 2012-11-22 | Bionomics Limited | Amine derivatives as potassium channel blockers |
CN105646362B (zh) | 2011-07-26 | 2019-07-05 | 赛诺菲 | 3-杂芳酰基氨基-丙酸衍生物及其作为药物的用途 |
US9586914B2 (en) | 2011-11-07 | 2017-03-07 | The University Of Queensland | Modulators of C3a receptors |
IN2015DN03969A (zh) | 2012-10-17 | 2015-10-02 | Univ Bristol | |
GB201300304D0 (en) * | 2013-01-08 | 2013-02-20 | Kalvista Pharmaceuticals Ltd | Benzylamine derivatives |
WO2017070235A1 (en) * | 2015-10-19 | 2017-04-27 | Attenua, Inc. | Antitussive compositions and methods |
EP3679027A1 (en) | 2017-09-04 | 2020-07-15 | C4 Therapeutics, Inc. | Dihydrobenzimidazolones |
WO2020181232A1 (en) | 2019-03-06 | 2020-09-10 | C4 Therapeutics, Inc. | Heterocyclic compounds for medical treatment |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3499002A (en) * | 1968-06-20 | 1970-03-03 | Robins Co Inc A H | 1-carbamoyl-3-aroylpyrrolidines |
NL6913261A (zh) * | 1968-09-09 | 1970-03-11 | ||
US3932444A (en) * | 1972-04-28 | 1976-01-13 | E. I. Du Pont De Nemours & Co. | 4-Imidazolylsulfonylimidazoles |
US4013647A (en) * | 1976-03-23 | 1977-03-22 | American Home Products Corporation | Morpholine containing tetrazole-5-carboxamide derivatives |
GB1491776A (en) * | 1976-09-08 | 1977-11-16 | Pfizer Ltd | Thiadiazoles |
US4076718A (en) * | 1977-01-21 | 1978-02-28 | American Home Products Corporation | 2,6-Pyridinediyl-bis-tetrazol-5-carboxamides |
US5236928A (en) * | 1991-03-19 | 1993-08-17 | Merck & Co., Inc. | Imidazole derivatives bearing acidic functional groups at the 5-position, their compositions and methods of use as angiotensin II antagonists |
CA2112566A1 (en) | 1991-07-01 | 1993-02-18 | Graham J. Moore | Non-desensitizing analogs of gnrh and other biologically active ligands |
CA2126976A1 (en) * | 1991-12-31 | 1993-07-08 | Hisashi Takasugi | Oxadiazole derivatives having acetylcholinesterase-inhibitory and muscarinic agonist activity |
ATE243204T1 (de) * | 1995-08-24 | 2003-07-15 | Basf Ag | Isoxazole- und isothiazole-5-carboxamid derivate, deren herstellung und deren verwendung als herbizide |
NZ325060A (en) * | 1995-12-14 | 2000-02-28 | Merck & Co Inc | Non peptide indole derivative and their use as antagonists of gonadotropin releasing hormone |
WO1997044339A1 (en) * | 1996-05-20 | 1997-11-27 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
US5878393A (en) * | 1996-09-09 | 1999-03-02 | Matsushita Electric Industrial Co., Ltd. | High quality concatenative reading system |
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1999
- 1999-08-20 PL PL99356984A patent/PL356984A1/xx unknown
- 1999-08-20 NZ NZ509252A patent/NZ509252A/en unknown
- 1999-08-20 ES ES99968010T patent/ES2237966T3/es not_active Expired - Lifetime
- 1999-08-20 EA EA200100255A patent/EA200100255A1/ru unknown
- 1999-08-20 KR KR1020017002021A patent/KR20010085402A/ko not_active Application Discontinuation
- 1999-08-20 TR TR2001/00631T patent/TR200100631T2/xx unknown
- 1999-08-20 HU HU0103622A patent/HUP0103622A3/hu unknown
- 1999-08-20 EP EP99968010A patent/EP1105120B1/en not_active Expired - Lifetime
- 1999-08-20 JP JP2000574479A patent/JP2002535244A/ja active Pending
- 1999-08-20 EE EEP200100102A patent/EE200100102A/xx unknown
- 1999-08-20 CZ CZ2001523A patent/CZ2001523A3/cs unknown
- 1999-08-20 CA CA002341346A patent/CA2341346A1/en not_active Abandoned
- 1999-08-20 AP APAP/P/2001/002053A patent/AP2001002053A0/en unknown
- 1999-08-20 BR BR9913374-1A patent/BR9913374A/pt not_active IP Right Cessation
- 1999-08-20 DE DE69924387T patent/DE69924387D1/de not_active Expired - Fee Related
- 1999-08-20 AU AU24709/00A patent/AU759310B2/en not_active Ceased
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- 1999-08-20 ID IDW20010406A patent/ID29244A/id unknown
- 1999-08-20 SK SK226-2001A patent/SK2262001A3/sk unknown
- 1999-08-20 WO PCT/US1999/018790 patent/WO2000020358A2/en not_active Application Discontinuation
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2001
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- 2001-01-30 ZA ZA200100831A patent/ZA200100831B/en unknown
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