ES2309400T3 - Compuestos de pirrolidina y azetidina como antagonistas de ccr5. - Google Patents
Compuestos de pirrolidina y azetidina como antagonistas de ccr5. Download PDFInfo
- Publication number
- ES2309400T3 ES2309400T3 ES03813415T ES03813415T ES2309400T3 ES 2309400 T3 ES2309400 T3 ES 2309400T3 ES 03813415 T ES03813415 T ES 03813415T ES 03813415 T ES03813415 T ES 03813415T ES 2309400 T3 ES2309400 T3 ES 2309400T3
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- Prior art keywords
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- bis
- hydroxy
- inhibitors
- dichlorophenyl
- 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 - Lifetime
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- 239000005557 antagonist Substances 0.000 title claims description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title description 17
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical class C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 title 1
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Landscapes
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Applications Claiming Priority (2)
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| US43337202P | 2002-12-13 | 2002-12-13 | |
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| ES03813415T Expired - Lifetime ES2309400T3 (es) | 2002-12-13 | 2003-12-12 | Compuestos de pirrolidina y azetidina como antagonistas de ccr5. |
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| WO2004054581A2 (en) * | 2002-12-13 | 2004-07-01 | Smithkline Beecham Corporation | Cyclohexyl compounds as ccr5 antagonists |
| GB0417801D0 (en) * | 2004-08-10 | 2004-09-15 | Novartis Ag | Organic compounds |
| US7745427B2 (en) | 2004-10-22 | 2010-06-29 | Merck Sharp & Dohme Corp. | CGRP receptor antagonists |
| CA2615656A1 (en) * | 2005-07-18 | 2007-01-25 | Merck & Co., Inc. | Spiropiperidine beta-secretase inhibitors for the treatment of alzheimer's disease |
| WO2008030853A2 (en) * | 2006-09-06 | 2008-03-13 | Incyte Corporation | Combination therapy for human immunodeficiency virus infection |
| ES2345130T3 (es) * | 2006-09-18 | 2010-09-15 | F. Hoffmann-La Roche Ag | Derivados de octahidropirrolo(3,4-c)pirrol y su uso como antiviricos. |
| DK2114925T3 (da) * | 2006-12-22 | 2012-05-29 | Ind Res Ltd | Azetidin-analoger af nucleosidase- og phosphorylase-inhibitorer |
| BRPI0913291A2 (pt) | 2008-05-30 | 2019-01-15 | Takeda Pharmaceuticals Co | composto, pró-droga, medicamento, métodos para diminuir a proteína 4 ou tratamento de diabete em um mamífero, e, uso do composto |
| UA103195C2 (uk) | 2008-08-11 | 2013-09-25 | Глаксосмитклайн Ллк | Похідні пурину для застосування у лікуванні алергій, запальних та інфекційних захворювань |
| BRPI0917458A2 (pt) | 2008-08-11 | 2015-12-01 | Glaxosmithkline Llc | composto, método de tratamento de doenças e condições, composição farmacêutica, método para tratar ou prevenir doença, e, uso de um composto |
| CN102176911B (zh) | 2008-08-11 | 2014-12-10 | 葛兰素史密丝克莱恩有限责任公司 | 新的腺嘌呤衍生物 |
| US8575340B2 (en) | 2010-02-10 | 2013-11-05 | Glaxosmithkline Llc | Purine derivatives and their pharmaceutical uses |
| RS53745B1 (sr) | 2010-02-10 | 2015-06-30 | Glaxosmithkline Llc | 6-amino-2-{[(1s)-1-metilbutil]oksi}-9-[5-(1-piperidinil)pentil]-7,9-dihidro-8h-purin-8-on-maleat |
| JO3387B1 (ar) | 2011-12-16 | 2019-03-13 | Glaxosmithkline Llc | مشتقات بيتولين |
| KR20160124157A (ko) | 2014-02-20 | 2016-10-26 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 인간 인터페론의 유도인자로서의 피롤로[3,2]피리미딘 유도체 |
| ES2917887T3 (es) | 2014-11-13 | 2022-07-12 | Glaxosmithkline Biologicals Sa | Derivados de adenina que son útiles en el tratamiento de enfermedades alérgicas u otras afecciones inflamatorias |
| TW201712012A (zh) * | 2015-06-16 | 2017-04-01 | 美國禮來大藥廠 | ２－側氧基－１，３，８－三氮雜螺［４．５］癸－３－基羧酸衍生物 |
| JP6411676B2 (ja) | 2015-12-03 | 2018-10-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | Ｓｔｉｎｇの調節因子としての環状プリンジヌクレオチド |
| SG10201900628RA (en) | 2016-04-07 | 2019-02-27 | Glaxosmithkline Ip Dev Ltd | Heterocyclic amides useful as protein modulators |
| WO2017175156A1 (en) | 2016-04-07 | 2017-10-12 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides useful as protein modulators |
| US11377440B2 (en) | 2017-10-05 | 2022-07-05 | Glaxosmithkline Intellectual Property Development Limited | Modulators of stimulator of interferon genes (STING) |
| AU2018344902B2 (en) | 2017-10-05 | 2021-06-03 | Glaxosmithkline Intellectual Property Development Limited | Modulators of stimulator of interferon genes (STING) useful in treating HIV |
| GB201807924D0 (en) | 2018-05-16 | 2018-06-27 | Ctxt Pty Ltd | Compounds |
| AU2019387370A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| JP2022533390A (ja) | 2019-05-16 | 2022-07-22 | スティングセラ インコーポレイテッド | オキソアクリジニル酢酸誘導体および使用方法 |
| US20220251079A1 (en) | 2019-05-16 | 2022-08-11 | Stingthera, Inc. | Benzo[b][1,8]naphthyridine acetic acid derivatives and methods of use |
| GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| WO2021119753A1 (en) | 2019-12-18 | 2021-06-24 | Ctxt Pty Limited | Compounds |
| US11116737B1 (en) | 2020-04-10 | 2021-09-14 | University Of Georgia Research Foundation, Inc. | Methods of using probenecid for treatment of coronavirus infections |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994026735A1 (en) * | 1993-05-06 | 1994-11-24 | Merrell Dow Pharmaceuticals Inc. | Substituted pyrrolidin-3-yl-alkyl-piperidines useful as tachykinin antagonists |
| US5635510A (en) | 1993-05-06 | 1997-06-03 | Merrell Pharmaceuticals Inc. | Substituted pyrrolidin-3-yl-alkyl-piperidines |
| WO1995028389A1 (en) * | 1994-04-15 | 1995-10-26 | Yamanouchi Pharmaceutical Co., Ltd. | Spiro compound and medicinal composition thereof |
| US5861417A (en) | 1996-12-19 | 1999-01-19 | Hoechst Marion Roussel, Inc. | Heterocyclic substituted pyrrolidine amide derivatives |
| US7053090B2 (en) * | 2001-03-19 | 2006-05-30 | Ono Pharmaceutical Co., Ltd. | Triazaspiro[5.5]undecane derivatives and drugs containing the same as the active ingredient |
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- 2003-12-12 WO PCT/US2003/039618 patent/WO2004055016A1/en not_active Ceased
- 2003-12-12 ES ES03813415T patent/ES2309400T3/es not_active Expired - Lifetime
- 2003-12-12 JP JP2004560830A patent/JP2006511552A/ja active Pending
- 2003-12-12 US US10/538,134 patent/US7271172B2/en not_active Expired - Fee Related
- 2003-12-12 EP EP03813415A patent/EP1569933B1/en not_active Expired - Lifetime
- 2003-12-12 AT AT03813415T patent/ATE402176T1/de not_active IP Right Cessation
- 2003-12-12 AU AU2003296992A patent/AU2003296992A1/en not_active Abandoned
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| DE60322423D1 (de) | 2008-09-04 |
| EP1569933B1 (en) | 2008-07-23 |
| JP2006511552A (ja) | 2006-04-06 |
| US7271172B2 (en) | 2007-09-18 |
| EP1569933A1 (en) | 2005-09-07 |
| US20060058284A1 (en) | 2006-03-16 |
| WO2004055016A1 (en) | 2004-07-01 |
| ATE402176T1 (de) | 2008-08-15 |
| AU2003296992A1 (en) | 2004-07-09 |
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