SK15712003A3 - Ligandy receptora 5-HT a ich použitie - Google Patents
Ligandy receptora 5-HT a ich použitie Download PDFInfo
- Publication number
- SK15712003A3 SK15712003A3 SK1571-2003A SK15712003A SK15712003A3 SK 15712003 A3 SK15712003 A3 SK 15712003A3 SK 15712003 A SK15712003 A SK 15712003A SK 15712003 A3 SK15712003 A3 SK 15712003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- carbon atoms
- piperazin
- pyrimidine
- compound
- Prior art date
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Landscapes
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| US29995301P | 2001-06-21 | 2001-06-21 | |
| PCT/IB2002/002261 WO2003000663A1 (en) | 2001-06-21 | 2002-06-17 | 5-ht receptor ligands and uses thereof |
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| SK15712003A3 true SK15712003A3 (sk) | 2004-06-08 |
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| US7456184B2 (en) * | 2003-05-01 | 2008-11-25 | Palatin Technologies Inc. | Melanocortin receptor-specific compounds |
| US7718802B2 (en) | 2001-08-10 | 2010-05-18 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| US7732451B2 (en) * | 2001-08-10 | 2010-06-08 | Palatin Technologies, Inc. | Naphthalene-containing melanocortin receptor-specific small molecule |
| US7354923B2 (en) * | 2001-08-10 | 2008-04-08 | Palatin Technologies, Inc. | Piperazine melanocortin-specific compounds |
| US7655658B2 (en) * | 2001-08-10 | 2010-02-02 | Palatin Technologies, Inc. | Thieno [2,3-D]pyrimidine-2,4-dione melanocortin-specific compounds |
| JP2005504043A (ja) * | 2001-08-10 | 2005-02-10 | パラチン テクノロジーズ インク. | 生物学的に活性な金属ペプチド類のペプチド模倣体類 |
| US6953787B2 (en) | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
| US7226925B2 (en) | 2002-06-19 | 2007-06-05 | Biovitrum Ab | Compounds, their use and preparation |
| NZ536664A (en) | 2002-06-19 | 2007-07-27 | Biovitrum Ab | Piperazinylpyrazine derivative compounds, their use and preparation |
| ES2295816T3 (es) | 2003-01-14 | 2008-04-16 | Arena Pharmaceuticals, Inc. | Derivados arilo y heteroarilo 1,2,3-trisustituidos como moduladores del metabolismo, y profilaxis y tratamiento de transtornos relacionados con los mismos, tales como la diabetes y la hiperglucemia. |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| DK1603893T3 (da) * | 2003-01-29 | 2008-09-08 | Asterand Uk Ltd | EP4 -Receptorantagonister |
| CN103265477B (zh) | 2003-02-26 | 2017-01-11 | 苏根公司 | 作为蛋白激酶抑制剂的氨基杂芳基化合物 |
| US20040235856A1 (en) * | 2003-04-25 | 2004-11-25 | Pfizer Inc | Treatment of incontinence |
| CL2004000826A1 (es) * | 2003-04-25 | 2005-03-04 | Pfizer | Uso de un agonista para el receptor 5-ht2c para preparar un medicamento util en el tratamiento de la incontinencia urinaria provocada por estres, con la condicion de que el agonista no sea 1-[6-cloro-5-(trifluorometil)-2-piridinil]piperazina (org-129 |
| US20080146583A1 (en) * | 2003-05-15 | 2008-06-19 | Pfizer Inc | Treatment of Incontinence |
| US7968548B2 (en) | 2003-05-01 | 2011-06-28 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine compounds with diamine groups |
| US7727991B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific single acyl piperazine compounds |
| US7727990B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine and keto-piperazine compounds |
| JP4782003B2 (ja) | 2003-06-17 | 2011-09-28 | アリーナ ファーマシューティカルズ, インコーポレイテッド | 5ht2cレセプター関連疾患の処置に有用なベンズアゼピン誘導体 |
| EP2332921B1 (en) | 2003-06-17 | 2016-03-02 | Arena Pharmaceuticals, Inc. | 8-Chloro-1 -methyl-2,3,4,5-tetrahydro-1 H-3benzazapine Hydrochloride |
| CN1809545A (zh) * | 2003-06-20 | 2006-07-26 | 艾尼纳制药公司 | N-苯基-哌嗪衍生物和预防或者治疗5HT2c受体相关疾病的方法 |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| US7132426B2 (en) | 2003-07-14 | 2006-11-07 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| CA2540640A1 (en) * | 2003-09-30 | 2005-04-14 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| WO2005053688A1 (en) | 2003-11-26 | 2005-06-16 | Alcon, Inc. | Substituted furo[2,3-g] indazoles for the treatment of glaucoma |
| US7338972B1 (en) | 2003-12-15 | 2008-03-04 | Alcon, Inc. | Substituted 1-alkylamino-1H-indazoles for the treatment of glaucoma |
| EP1694670A1 (en) * | 2003-12-16 | 2006-08-30 | GPC Biotech AG | Pyrazine derivatives as effective compounds against infectious diseases |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| US7709484B1 (en) | 2004-04-19 | 2010-05-04 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| ATE415397T1 (de) * | 2004-06-04 | 2008-12-15 | Arena Pharm Inc | Substituierte aryl- und heteroarylderivate als modulatoren des stoffwechsels und für die prophylaxe und behandlung von damit in zusammenhang stehenden erkrankungen |
| JP5173190B2 (ja) | 2004-08-25 | 2013-03-27 | 武田薬品工業株式会社 | 腹圧性尿失禁の予防・治療剤及びそのスクリーニング方法 |
| US8114502B2 (en) * | 2004-09-02 | 2012-02-14 | 3M Innovative Properties Company | Substrates with multiple images |
| AU2005305036B2 (en) * | 2004-11-01 | 2011-03-10 | Amylin Pharmaceuticals, Llc | Treatment of obesity and related disorders |
| EP2286837A3 (en) * | 2004-11-01 | 2013-09-04 | Amylin Pharmaceuticals, LLC | Treatment of obesity and obesity related diseases |
| US8394765B2 (en) | 2004-11-01 | 2013-03-12 | Amylin Pharmaceuticals Llc | Methods of treating obesity with two different anti-obesity agents |
| AR051946A1 (es) * | 2004-11-05 | 2007-02-21 | Wyeth Corp | Formulaciones de derivados de [1,4] diazepina [6,7,1-ij] quinolina |
| RU2007122485A (ru) | 2004-11-17 | 2008-12-27 | Мийкана Терапьютикс | Ингибиторы киназы |
| EP1844792A4 (en) * | 2004-12-14 | 2008-05-21 | Shionogi & Co | THERAPEUTIC AGENT AGAINST OBSTIPATION |
| NZ555981A (en) | 2004-12-21 | 2011-01-28 | Arena Pharm Inc | Crystalline forms of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride |
| EP2111859A1 (en) | 2004-12-23 | 2009-10-28 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulator compositions and methods of use |
| RU2440996C2 (ru) * | 2005-01-25 | 2012-01-27 | Галенеа Корп. | Замещенные ариламины и их применение в качестве модуляторов 5-ht6-рецептора |
| WO2006103511A1 (en) * | 2005-03-31 | 2006-10-05 | Pfizer Products Inc. | Cyclopentapyridine and tetrahydroquinoline derivatives |
| US7594976B2 (en) * | 2005-05-13 | 2009-09-29 | 3M Innovative Properties Company | Methods of manufacturing substrates |
| AU2006275702A1 (en) | 2005-07-29 | 2007-02-08 | Concert Pharmaceuticals Inc. | Novel pharmaceutical compounds |
| AU2006297120B2 (en) * | 2005-09-30 | 2011-05-19 | Miikana Therapeutics, Inc. | Substituted pyrazole compounds |
| EP1963302B1 (en) * | 2005-12-05 | 2013-02-27 | Pfizer Products Inc. | Polymorphs of a c-met/hgfr inhibitor |
| KR101026676B1 (ko) * | 2005-12-05 | 2011-04-04 | 화이자 프로덕츠 인코포레이티드 | 비정상 세포 성장의 치료 방법 |
| KR20080081321A (ko) * | 2005-12-21 | 2008-09-09 | 쉐링 코포레이션 | H3 길항제/역 작용제 및 식욕 억제제의 조합물 |
| US8168782B2 (en) | 2006-04-03 | 2012-05-01 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and intermediates related thereto |
| WO2007132841A1 (ja) | 2006-05-16 | 2007-11-22 | Takeda Pharmaceutical Company Limited | 縮合複素環化合物およびその用途 |
| CN101448820A (zh) * | 2006-05-30 | 2009-06-03 | 霍夫曼-拉罗奇有限公司 | 哌啶基嘧啶衍生物 |
| DE602007012254D1 (de) * | 2006-07-14 | 2011-03-10 | Pfizer Prod Inc | Tartratsalz von (7s)-7-ä(5-fluor-2-methylbenzyl)oxyü-2-ä(2r)-2-methylpiperazin-1-ylü-6,7-dihydro-5h-cyclopentaäbüpyridin |
| US7834017B2 (en) | 2006-08-11 | 2010-11-16 | Palatin Technologies, Inc. | Diamine-containing, tetra-substituted piperazine compounds having identical 1- and 4-substituents |
| CN101583593A (zh) | 2006-11-13 | 2009-11-18 | 辉瑞产品公司 | 二芳基、二吡啶基和芳基-吡啶基衍生物及其用途 |
| PL2848610T3 (pl) * | 2006-11-15 | 2018-01-31 | Ym Biosciences Australia Pty | Inhibitory aktywności kinazy |
| JP5404414B2 (ja) | 2006-12-05 | 2014-01-29 | アリーナ ファーマシューティカルズ, インコーポレイテッド | (r)−8−クロロ−1−メチル−2,3,4,5−テトラヒドロ−1h−3−ベンゾアゼピンおよびその中間体を調製するための方法 |
| TWI629058B (zh) | 2007-01-16 | 2018-07-11 | 陳建宏 | 醫藥組成物及其用途 |
| US20080220104A1 (en) * | 2007-03-08 | 2008-09-11 | Cappello John V | Compositions for producing satiety |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| WO2008151257A2 (en) | 2007-06-04 | 2008-12-11 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP2166849A4 (en) * | 2007-06-11 | 2010-09-15 | Miikana Therapeutics Inc | SUBSTITUTED PYRAZOL COMPOUNDS |
| WO2009063992A1 (ja) | 2007-11-15 | 2009-05-22 | Takeda Pharmaceutical Company Limited | 縮合ピリジン誘導体およびその用途 |
| CN102015591B (zh) * | 2008-03-04 | 2014-01-29 | 艾尼纳制药公司 | 制备与5-ht2c激动剂(r)-8-氯-1-甲基-2,3,4,5-四氢-1h-3-苯并氮杂卓相关的中间体的方法 |
| WO2009149279A2 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EA018198B1 (ru) | 2008-06-12 | 2013-06-28 | Янссен Фармацевтика Нв | Диаминопиридиновые, пиримидиновые и пиридазиновые модуляторы гистаминового рецептора h |
| EP2303275A4 (en) * | 2008-06-17 | 2012-05-09 | Univ Duke | STANDARD RECEPTOR MODULATORS |
| CA2730603C (en) | 2008-07-16 | 2019-09-24 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| CA2741125A1 (en) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| WO2010051206A1 (en) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| AU2009314200B2 (en) | 2008-11-17 | 2011-11-17 | Merck Sharp & Dohme Corp. | Substituted bicyclic amines for the treatment of diabetes |
| CN102648170A (zh) | 2009-06-18 | 2012-08-22 | 艾尼纳制药公司 | 制备5-ht2c受体激动剂的方法 |
| SG176645A1 (en) * | 2009-06-26 | 2012-01-30 | Sanofi Sa | Novel fumarate salts of a histamine h3 receptor antagonist |
| WO2011011508A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
| WO2011011506A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Spirocyclic oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
| JPWO2011071136A1 (ja) | 2009-12-11 | 2013-04-22 | アステラス製薬株式会社 | 線維筋痛症治療剤 |
| US8895596B2 (en) | 2010-02-25 | 2014-11-25 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| WO2011137024A1 (en) | 2010-04-26 | 2011-11-03 | Merck Sharp & Dohme Corp. | Novel spiropiperidine prolylcarboxypeptidase inhibitors |
| US9365539B2 (en) | 2010-05-11 | 2016-06-14 | Merck Sharp & Dohme Corp. | Prolylcarboxypeptidase inhibitors |
| KR20130112848A (ko) | 2010-06-02 | 2013-10-14 | 아레나 파마슈티칼스, 인크. | 5-ht2c 수용체 아고니스트의 제조 방법 |
| US9006268B2 (en) | 2010-06-11 | 2015-04-14 | Merck Sharp & Dohme Corp. | Prolylcarboxypeptidase inhibitors |
| EP2585216B1 (en) * | 2010-06-23 | 2019-11-20 | Johnson Matthey PLC | Pi-allylpalladium and pi-allylnickel complexes for use as catalysts in carbon-carbon and carbon-nitrogen coupling reactions |
| JP2013536859A (ja) | 2010-09-01 | 2013-09-26 | アリーナ ファーマシューティカルズ, インコーポレイテッド | 5−ht2cアゴニストの非吸湿性塩 |
| US20130315994A1 (en) | 2010-09-01 | 2013-11-28 | Zezhi Jesse Shao | Modified-release dosage forms of 5-ht2c agonists useful for weight management |
| CA2808909A1 (en) | 2010-09-01 | 2012-03-08 | Arena Pharmaceuticals, Inc. | Salts of lorcaserin with optically active acids |
| SG10201506896RA (en) | 2010-09-01 | 2015-10-29 | Arena Pharm Inc | Administration of lorcaserin to individuals with renal impairment |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| EP2619198A1 (en) | 2010-09-22 | 2013-07-31 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| ES2587304T3 (es) * | 2011-02-25 | 2016-10-21 | Yuhan Corporation | Derivados de diaminopirimidina y procedimientos para la preparación de los mismos |
| BR112013021236B1 (pt) | 2011-02-25 | 2021-05-25 | Merck Sharp & Dohme Corp | composto derivado de benzimidazol, e, composição |
| KR20150023318A (ko) * | 2012-05-30 | 2015-03-05 | 에프. 호프만-라 로슈 아게 | 피롤리디노 헤테로사이클 |
| US9527875B2 (en) | 2012-08-02 | 2016-12-27 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| MY181736A (en) | 2012-10-09 | 2021-01-05 | Arena Pharm Inc | Method of weight management |
| AU2014205483B2 (en) | 2013-01-10 | 2017-11-30 | Gilead Sciences, Inc. | Non-selective kinase inhibitors |
| MX2015010935A (es) | 2013-02-22 | 2015-10-29 | Merck Sharp & Dohme | Compuestos biciclicos antidiabeticos. |
| US9650375B2 (en) | 2013-03-14 | 2017-05-16 | Merck Sharp & Dohme Corp. | Indole derivatives useful as anti-diabetic agents |
| EP2970384A1 (en) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| WO2014151200A2 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| AU2014274812B2 (en) | 2013-06-05 | 2018-09-27 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase C, method of making and using same |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| JP6483714B2 (ja) | 2013-10-11 | 2019-03-13 | ローレンス エス. ジスマン, | 噴霧乾燥製剤 |
| WO2015066344A1 (en) | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists and compositions and methods of use |
| PL3242666T3 (pl) | 2015-01-06 | 2025-02-17 | Arena Pharmaceuticals, Inc. | Związek do zastosowania w leczeniu dolegliwości związanych z receptorem s1p1 |
| JP6838744B2 (ja) | 2015-06-22 | 2021-03-03 | アリーナ ファーマシューティカルズ, インコーポレイテッド | S1P1レセプター関連障害における使用のための(R)−2−(7−(4−シクロペンチル−3−(トリフルオロメチル)ベンジルオキシ)−1,2,3,4−テトラヒドロシクロペンタ[b]インドール−3−イル)酢酸(化合物1)の結晶性L−アルギニン塩 |
| WO2018081567A1 (en) | 2016-10-27 | 2018-05-03 | Pulmokine, Inc. | Combination therapy for treating pulmonary hypertension |
| EP3551176A4 (en) | 2016-12-06 | 2020-06-24 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| WO2018118670A1 (en) | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
| AU2018220521A1 (en) | 2017-02-16 | 2019-09-05 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| JPWO2019131902A1 (ja) | 2017-12-27 | 2020-12-10 | 武田薬品工業株式会社 | 腹圧性尿失禁および便失禁の治療薬 |
| KR102859841B1 (ko) | 2018-06-06 | 2025-09-12 | 아레나 파마슈티칼스, 인크. | S1p1 수용체와 관련된 병태의 치료 방법 |
| EP3934633A4 (en) * | 2019-03-07 | 2023-03-29 | Arbormentis LLC | COMPOSITIONS AND METHODS OF USE WITH SUBSTANCES WITH NEURAL PLASTIC EFFECTS ADMINISTRATED IN NON-PSYCHEDELIC/PSYCHOTOMIMETIC DOSES AND FORMULATIONS |
| CN111704582B (zh) * | 2020-06-23 | 2021-06-11 | 杭州煌森生物科技有限公司 | 一种法匹拉韦及其衍生物的制备方法 |
| CN115618396B (zh) * | 2022-11-28 | 2023-04-07 | 云账户技术(天津)有限公司 | 一种数据的加密方法及装置 |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL127996C (et) * | 1963-11-19 | |||
| US3980781A (en) * | 1966-03-31 | 1976-09-14 | Imperial Chemical Industries Limited | Fungicidal composition and method containing 2-amino-pyrimidines |
| GB1165283A (en) * | 1967-01-17 | 1969-09-24 | Science Union & Cie | New Purine Derivatives and processes for prepararing them |
| US4166852A (en) * | 1974-08-09 | 1979-09-04 | Produits Chimiques Ugine Kuhlmann | Piperazino-pyrimidines and their use as spasmolytic agents |
| FR2281117A2 (fr) | 1974-08-09 | 1976-03-05 | Ugine Kuhlmann | Nouvelles piperazino-pyrimidines utilisables comme medicaments |
| US4081542A (en) * | 1975-04-21 | 1978-03-28 | Merck & Co., Inc. | Piperazinylpyrazines |
| SE421695B (sv) * | 1975-04-21 | 1982-01-25 | Merck & Co Inc | Sett att framstella piperazinylpyraziner |
| FR2311776A1 (fr) * | 1975-05-23 | 1976-12-17 | Sogeras | Diamino-2,4 bromo-5 chloro-6 pyrimidines et procede pour leur preparation |
| FI70411C (fi) * | 1980-12-29 | 1986-09-19 | Pfizer | Foerfarande foer framstaellning av nya antihypertensiva 4-amino-6,7-dimetoxi-2-piperazinokinazolin derivat |
| HU206337B (en) * | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
| DE3905364A1 (de) * | 1989-02-22 | 1990-08-23 | Hoechst Ag | Substituierte pyrimidin-derivate, verfahren zu ihrer herstellung und ihre verwendung als tool |
| GB9012592D0 (en) | 1990-06-06 | 1990-07-25 | Smithkline Beecham Intercredit | Compounds |
| JPH0665203A (ja) * | 1992-06-25 | 1994-03-08 | Elf Sanofi | ピペラジンのヘテロ環誘導体 |
| WO1994007867A1 (en) | 1992-09-28 | 1994-04-14 | Pfizer Inc. | Substituted pyrimidines for control of diabetic complications |
| CN1142817A (zh) * | 1993-10-12 | 1997-02-12 | 杜邦麦克制药有限公司 | 1n-烷基-n-芳基嘧啶胺及其衍生物 |
| EP0723533A1 (en) * | 1993-10-12 | 1996-07-31 | The Du Pont Merck Pharmaceutical Company | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
| US5419301A (en) * | 1994-04-14 | 1995-05-30 | Ford Motor Company | Adaptive control of camless valvetrain |
| EP0826674A4 (en) | 1995-04-03 | 1998-07-08 | Sumitomo Pharma | EFFECTIVE PYRIMIDINE DERIVATIVES AS PSYCHOTROPE, AND METHOD FOR THE PRODUCTION THEREOF |
| US5795905A (en) | 1995-06-06 | 1998-08-18 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods relating thereto |
| ES2174176T3 (es) * | 1996-02-29 | 2002-11-01 | Pfizer | Procedimiento para reducir el daño en tejido asociado con la isquemia. |
| US6326368B1 (en) * | 1996-03-27 | 2001-12-04 | Dupont Pharmaceuticals Company | Aryloxy- and arylthiosubstituted pyrimidines and triazines and derivatives thereof |
| TW440563B (en) * | 1996-05-23 | 2001-06-16 | Hoffmann La Roche | Aryl pyrimidine derivatives and a pharmaceutical composition thereof |
| KR100239800B1 (ko) * | 1996-11-28 | 2000-03-02 | 손경식 | 4,5-디아미노 피리미딘 유도체 및 이의 제조방법 |
| DE19710435A1 (de) * | 1997-03-13 | 1998-09-17 | Hoechst Ag | Verwendung von Pyrimidinderivaten zur Prävention von Krebs allein oder in Kombination mit anderen therapeutischen Maßnahmen |
| US6440965B1 (en) * | 1997-10-15 | 2002-08-27 | Krenitsky Pharmaceuticals, Inc. | Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system |
| AU1738900A (en) | 1998-11-19 | 2000-06-05 | Nortran Pharmaceuticals Inc. | Serotonin ligands as pro-erectile compounds |
| GB9902047D0 (en) | 1999-01-29 | 1999-03-17 | Cerebrus Ltd | Chemical compounds XI |
| ATE313535T1 (de) | 1999-05-21 | 2006-01-15 | Pyrazinyl-piperazin-verbindungen, ihre anwendung und herstellung | |
| SE0002754D0 (sv) | 2000-07-21 | 2000-07-21 | Pharmacia & Upjohn Ab | New pharmaceutical combination formulation and method of treatment with the combination |
| CN1267424C (zh) | 2000-11-20 | 2006-08-02 | 比奥维特罗姆股份公司 | 作为5-羟色胺5ht-2受体的激动剂或拮抗剂的哌嗪基吡嗪化合物 |
| SE0004245D0 (sv) * | 2000-11-20 | 2000-11-20 | Pharmacia Ab | Novel compounds and their use |
| KR100831909B1 (ko) | 2000-11-20 | 2008-05-26 | 바이오비트럼 에이비(피유비엘) | 세로토닌 5-ht2 수용체의 안타고니스트로서의피페라지닐피라진 화합물 |
-
2002
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- 2002-06-05 DO DO2002000412A patent/DOP2002000412A/es unknown
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- 2002-06-14 GT GT200200120A patent/GT200200120A/es unknown
- 2002-06-17 PL PL02367777A patent/PL367777A1/xx not_active Application Discontinuation
- 2002-06-17 OA OA1200300319A patent/OA12621A/en unknown
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- 2002-06-17 SK SK1571-2003A patent/SK15712003A3/sk not_active Application Discontinuation
- 2002-06-17 AU AU2002309173A patent/AU2002309173B2/en not_active Ceased
- 2002-06-17 WO PCT/IB2002/002261 patent/WO2003000663A1/en not_active Ceased
- 2002-06-17 JP JP2003507071A patent/JP2005501821A/ja not_active Abandoned
- 2002-06-17 SK SK1567-2003A patent/SK15672003A3/sk unknown
- 2002-06-17 TN TNPCT/IB2002/002261A patent/TNSN03143A1/fr unknown
- 2002-06-17 BR BR0210503-9A patent/BR0210503A/pt not_active IP Right Cessation
- 2002-06-17 NZ NZ529542A patent/NZ529542A/en unknown
- 2002-06-17 HR HR20031042A patent/HRP20031042A2/hr not_active Application Discontinuation
- 2002-06-17 WO PCT/IB2002/002293 patent/WO2003000666A1/en not_active Ceased
- 2002-06-17 EA EA200301213A patent/EA200301213A1/ru unknown
- 2002-06-17 EE EEP200400026A patent/EE200400026A/et unknown
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- 2002-06-17 OA OA1200300330A patent/OA12629A/en unknown
- 2002-06-17 PL PL02367746A patent/PL367746A1/xx not_active Application Discontinuation
- 2002-06-17 JP JP2003507068A patent/JP2004534823A/ja not_active Withdrawn
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