CN1671695A - 用作pde4抑制剂的吡咯烷二酮取代的哌啶－2,3－二氮杂萘酮化合物 - Google Patents
用作pde4抑制剂的吡咯烷二酮取代的哌啶－2,3－二氮杂萘酮化合物 Download PDFInfo
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- CN1671695A CN1671695A CNA038185202A CN03818520A CN1671695A CN 1671695 A CN1671695 A CN 1671695A CN A038185202 A CNA038185202 A CN A038185202A CN 03818520 A CN03818520 A CN 03818520A CN 1671695 A CN1671695 A CN 1671695A
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- tetramethyleneimine
- diketone
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110330465A (zh) * | 2019-06-28 | 2019-10-15 | 深圳市三启药物开发有限公司 | 腙酰胺类衍生物及其在制备防治脱发药物中的应用 |
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| MY140561A (en) | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
| RS52908B (sr) | 2003-03-10 | 2014-02-28 | Takeda Gmbh | Novi postupak za dobijanje roflumilasta |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| AU2005210042B2 (en) * | 2004-02-04 | 2011-04-21 | Takeda Gmbh | 2-(piperidin-4-yl) -4, 5-dihydro-2H-pyridazin-3-one derivatives as PDE4 inhibitors |
| EP1716123A1 (en) * | 2004-02-04 | 2006-11-02 | Altana Pharma AG | Pyridazinone derivatives and their use as pde4 inhibitors |
| EP1755595A1 (en) * | 2004-05-10 | 2007-02-28 | Altana Pharma AG | Use of roflumilast for the prophylaxis or treatment of emphysema |
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| CA2601250C (en) | 2005-03-16 | 2014-10-28 | Nycomed Gmbh | Taste masked dosage form containing roflumilast |
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| JP5006330B2 (ja) | 2005-10-21 | 2012-08-22 | ノバルティス アーゲー | Ｉｌ１３に対するヒト抗体および治療的使用 |
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| DK2104535T3 (da) | 2007-01-10 | 2011-04-04 | Irm Llc | Forbindelser og sammensætninger som kanalaktiverende proteaseinhibitorer |
| WO2008127898A1 (en) * | 2007-04-11 | 2008-10-23 | Martinez Rodolfo A | Single carbon precursor synthons |
| CN101687851B (zh) | 2007-05-07 | 2013-02-27 | 诺瓦提斯公司 | 有机化合物 |
| CN103463086B (zh) * | 2007-05-16 | 2015-10-21 | 塔科达有限责任公司 | 作为pde4抑制剂的吡唑啉酮衍生物 |
| EA017919B1 (ru) | 2007-12-10 | 2013-04-30 | Новартис Аг | Производные пиразин-2-карбоксамида для лечения заболеваний, которые поддаются лечению путем блокирования эпителиальных натриевых каналов |
| CN101910153B (zh) | 2008-01-11 | 2014-01-22 | 诺华股份有限公司 | 作为激酶抑制剂的嘧啶类 |
| EA201001848A1 (ru) | 2008-06-10 | 2011-08-30 | Новартис Аг | Производные пиразина в качестве блокаторов эпителиальных натриевых каналов |
| AR074318A1 (es) | 2008-11-14 | 2011-01-05 | Nycomed Gmbh | Derivados heterociclicos de pirazolona, composiciones farmaceuticas que los contienen y uso de los mismos para el tratamiento de enfermedades de las vias respiratorias. |
| JP2012516345A (ja) | 2009-01-29 | 2012-07-19 | ノバルティス アーゲー | 星細胞腫治療用置換ベンゾイミダゾール |
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| EA201200260A1 (ru) | 2009-08-12 | 2012-09-28 | Новартис Аг | Гетероциклические гидразоны и их применение для лечения рака и воспаления |
| UA111579C2 (uk) | 2009-08-17 | 2016-05-25 | Інтеллікіне Ллк | ГЕТЕРОЦИКЛІЧНІ ПОХІДНІ 2-АМІНОБЕНЗО[d]ОКСАЗОЛУ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ НА ЇХ ОСНОВІ ТА ЇХ ЗАСТОСУВАННЯ ДЛЯ ЛІКУВАННЯ ЗАХВОРЮВАННЯ, ПОВ'АНОГО З РІ3-КІНАЗОЮ |
| KR20120089463A (ko) | 2009-08-20 | 2012-08-10 | 노파르티스 아게 | 헤테로시클릭 옥심 화합물 |
| JP2013508414A (ja) | 2009-10-22 | 2013-03-07 | バーテックス ファーマシューティカルズ インコーポレイテッド | 嚢胞性線維症および他の慢性疾患の治療のための組成物 |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| EP2678016B1 (en) | 2011-02-23 | 2016-08-10 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
| SG192795A1 (en) | 2011-02-25 | 2013-09-30 | Irm Llc | Compounds and compositions as trk inhibitors |
| MX2013014888A (es) * | 2011-06-17 | 2014-02-27 | Takeda Gmbh | Novedosos derivados de ftalazinona-pirrolopirimidinacarboxamida. |
| UY34305A (es) | 2011-09-01 | 2013-04-30 | Novartis Ag | Derivados de heterociclos bicíclicos para el tratamiento de la hipertensión arterial pulmonar |
| AU2012310168B2 (en) | 2011-09-15 | 2015-07-16 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| CN103946221B (zh) | 2011-09-16 | 2016-08-03 | 诺华股份有限公司 | 用于治疗囊性纤维化的杂环化合物 |
| US9056867B2 (en) | 2011-09-16 | 2015-06-16 | Novartis Ag | N-substituted heterocyclyl carboxamides |
| US9174994B2 (en) | 2011-11-23 | 2015-11-03 | Intellikine, Llc | Enhanced treatment regimens using mTor inhibitors |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| KR102115047B1 (ko) | 2012-04-03 | 2020-05-26 | 노파르티스 아게 | 티로신 키나제 억제제들을 갖는 조합 제품 및 그의 용도 |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| CN105246482A (zh) | 2013-03-15 | 2016-01-13 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| KR20160145780A (ko) | 2014-04-24 | 2016-12-20 | 노파르티스 아게 | 포스파티딜이노시톨 3-키나제 억제제로서의 아미노 피리딘 유도체 |
| WO2015162461A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| BR112016024533A8 (pt) | 2014-04-24 | 2021-03-30 | Novartis Ag | derivados de amino pirazina como inibidores de fosfatidilinositol 3-cinase ou sal, seu uso, e composição e combinação farmacêuticas |
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| WO2016016822A1 (en) | 2014-07-31 | 2016-02-04 | Novartis Ag | Combination therapy |
| BR112021024668A2 (pt) | 2019-06-10 | 2022-05-31 | Novartis Ag | Derivado de piridina e pirazina para o tratamento de fc, dpoc e bronquiectasia |
| KR20220052934A (ko) | 2019-08-28 | 2022-04-28 | 노파르티스 아게 | 치환 1,3-페닐 헤테로아릴 유도체 및 질환 치료에서의 이의 용도 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE168101T1 (de) | 1990-10-16 | 1998-07-15 | Byk Gulden Lomberg Chem Fab | Arylpyridazinone |
| US5716954A (en) | 1991-10-09 | 1998-02-10 | Syntex U.S.A. Inc. | Benzopyridazinone and pyridopyridazinone compounds |
| IL103388A (en) | 1991-10-09 | 1997-09-30 | Syntex Inc | PYRIDO £2,3-d| PYRIDAZINONES AND PYRIDAZINETHIONES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| CZ141795A3 (en) | 1992-12-02 | 1995-11-15 | Pfizer | 4-substituted catechol diethers as such and for treating diseases and pharmaceutical preparations based thereon |
| DE19533975A1 (de) | 1995-09-14 | 1997-03-20 | Merck Patent Gmbh | Arylalkyl-diazinone |
| US5658940A (en) * | 1995-10-06 | 1997-08-19 | Celgene Corporation | Succinimide and maleimide cytokine inhibitors |
| BR9806752A (pt) * | 1997-01-15 | 2000-03-14 | Byk Gulden Lomberg Chem Fab | Ftalazinonas. |
| ES2216349T3 (es) | 1997-12-15 | 2004-10-16 | Altana Pharma Ag | Dihidrobenzofuranos. |
| AU1760399A (en) | 1997-12-15 | 1999-07-05 | Byk Gulden Lomberg Chemische Fabrik Gmbh | New phthalazinones |
| SI1070056T1 (en) | 1998-03-14 | 2004-12-31 | Altana Pharma Ag | Phthalazinone pde iii/iv inhibitors |
| AU7654200A (en) | 1999-09-14 | 2001-04-17 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phthalazinone derivatives as pd3/4 inhibitors |
| EP1228046B1 (en) | 1999-10-25 | 2007-09-26 | Nycomed GmbH | Phthalazinone derivatives as pde 4 inhibitors |
| WO2001030777A1 (en) | 1999-10-25 | 2001-05-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Tetrahydrothiopy ranphthalazinone derivatives as pde4 inhibitors |
| KR20030031907A (ko) | 2000-06-05 | 2003-04-23 | 알타나 파마 아게 | β-2-아드레날린 수용체 작동물질로서 뿐만 아니라ＰＤＥ4-억제제로서 효과적인 화합물 |
| WO2002064584A1 (en) * | 2001-02-15 | 2002-08-22 | Altana Pharma Ag | Phthalayinone-piperidino-derivatives as pde4 inhibitors |
| DE10112864A1 (de) * | 2001-03-16 | 2002-09-19 | Alstom Switzerland Ltd | Verfahren zum Zünden einer thermischen Turbomaschine |
| HUP0303469A3 (en) | 2001-04-25 | 2004-04-28 | Altana Pharma Ag | Phtalazinon-derivatives, their use and pharmaceutical compositions containing them |
| EE200300514A (et) | 2001-04-25 | 2004-02-16 | Altana Pharma Ag | Ftalasinoonid, nende kasutamine hingamisteede haigusnähte leevendavate ravimite valmistamiseks ningneid sisaldavad ravimid |
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2003
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- 2003-08-06 AU AU2003260376A patent/AU2003260376A1/en not_active Abandoned
- 2003-08-06 US US10/523,412 patent/US7220746B2/en not_active Expired - Fee Related
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- 2003-08-06 PL PL373645A patent/PL214701B1/pl unknown
- 2003-08-06 EP EP03792267A patent/EP1556049A1/en not_active Withdrawn
- 2003-08-06 US US10/523,111 patent/US20060094710A1/en not_active Abandoned
- 2003-08-06 JP JP2004530086A patent/JP4555684B2/ja not_active Expired - Fee Related
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110330465A (zh) * | 2019-06-28 | 2019-10-15 | 深圳市三启药物开发有限公司 | 腙酰胺类衍生物及其在制备防治脱发药物中的应用 |
| WO2020258972A1 (zh) * | 2019-06-28 | 2020-12-30 | 深圳市三启药物开发有限公司 | 腙酰胺类衍生物及其在制备防治脱发药物中的应用 |
| CN110330465B (zh) * | 2019-06-28 | 2021-05-11 | 深圳市三启药物开发有限公司 | 腙酰胺类衍生物及其在制备防治脱发药物中的应用 |
| CN113105411A (zh) * | 2019-06-28 | 2021-07-13 | 深圳市三启药物开发有限公司 | 腙酰胺类衍生物及药物组合物 |
| US12479809B2 (en) | 2019-06-28 | 2025-11-25 | Shenzhen Cell Inspire Pharmaceutical Development Co., Ltd. | Hydrazone amide derivative and application thereof in preparation of medicaments for preventing and treating alopecia |
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