JP2010520875A - Ｐ２ｘ７調節因子としてのビシクロヘテロアリール化合物およびその使用 - Google Patents
Ｐ２ｘ７調節因子としてのビシクロヘテロアリール化合物およびその使用 Download PDFInfo
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- JP2010520875A JP2010520875A JP2009552762A JP2009552762A JP2010520875A JP 2010520875 A JP2010520875 A JP 2010520875A JP 2009552762 A JP2009552762 A JP 2009552762A JP 2009552762 A JP2009552762 A JP 2009552762A JP 2010520875 A JP2010520875 A JP 2010520875A
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Classifications
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Landscapes
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Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
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| US90604907P | 2007-03-09 | 2007-03-09 | |
| US91808607P | 2007-03-15 | 2007-03-15 | |
| US91826107P | 2007-03-15 | 2007-03-15 | |
| US91812307P | 2007-03-15 | 2007-03-15 | |
| US91826007P | 2007-03-15 | 2007-03-15 | |
| US838507P | 2007-12-20 | 2007-12-20 | |
| US838607P | 2007-12-20 | 2007-12-20 | |
| US837007P | 2007-12-20 | 2007-12-20 | |
| US1067208P | 2008-01-10 | 2008-01-10 | |
| PCT/US2008/003175 WO2008112205A1 (en) | 2007-03-09 | 2008-03-07 | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
Publications (2)
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| JP2010520875A true JP2010520875A (ja) | 2010-06-17 |
| JP2010520875A5 JP2010520875A5 (enExample) | 2011-03-31 |
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| EP (1) | EP2124562B1 (enExample) |
| JP (1) | JP2010520875A (enExample) |
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| DK (1) | DK2124562T3 (enExample) |
| ES (1) | ES2576643T3 (enExample) |
| WO (1) | WO2008112205A1 (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009530304A (ja) * | 2006-03-16 | 2009-08-27 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
| JP2009542595A (ja) * | 2006-07-06 | 2009-12-03 | グラクソ グループ リミテッド | Ｐ２ｘ７受容体アンタゴニストとしての置換ｎ−フェニルメチル−５−オキソ−プロリン−２−アミドおよびそれらの使用方法 |
| JP2014520880A (ja) * | 2011-07-22 | 2014-08-25 | アクテリオン ファーマシューティカルズ リミテッド | Ｐ２ｘ７受容体アンタゴニストとしての複素環アミド誘導体 |
| JP2017520538A (ja) * | 2014-06-05 | 2017-07-27 | 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Ｍｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | 新規キノリン誘導体及び神経変性疾患におけるそれらの使用 |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2596532T3 (es) | 2006-03-16 | 2017-01-10 | Second Genome, Inc. | Compuestos de bicicloheteroarilo como moduladores de P2X7 y usos de los mismos |
| EP2001474B1 (en) | 2006-03-16 | 2016-03-09 | Second Genome, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
| US8212723B2 (en) * | 2008-08-27 | 2012-07-03 | Qualcomm Incorporated | Method and apparatus for determining at a predetermined granularity the direction and range of a transmitting mobile device |
| BR112014017735B1 (pt) | 2012-01-20 | 2022-06-28 | Idorsia Pharmaceuticals Ltd | Compostos derivados de amida heterocíclicos como antagonistas do receptor de p2x7, composição farmacêutica, e, uso de um composto |
| EP2931717B1 (en) | 2012-12-12 | 2016-12-07 | Actelion Pharmaceuticals Ltd. | Indole carboxamide derivatives as p2x7 receptor antagonists |
| CA2891499C (en) | 2012-12-18 | 2021-07-06 | Actelion Pharmaceuticals Ltd | Indole carboxamide derivatives as p2x7 receptor antagonists |
| CN104918617B (zh) | 2013-01-22 | 2017-05-10 | 埃科特莱茵药品有限公司 | 作为p2x7受体拮抗剂的杂环酰胺衍生物 |
| JP6282017B2 (ja) | 2013-01-22 | 2018-02-21 | イドーシア ファーマシューティカルズ リミテッドＩｄｏｒｓｉａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｌｔｄ | Ｐ２ｘ７受容体アンタゴニストとしての複素環アミド誘導体 |
| TWI825637B (zh) | 2021-03-31 | 2023-12-11 | 美商輝瑞股份有限公司 | 啶－１，６（２ｈ，７ｈ）－二酮 |
| WO2025057074A1 (en) * | 2023-09-13 | 2025-03-20 | Suven Life Sciences Limited | N-aryl benzamide derivatives as p2x7 receptor antagonists |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006102588A1 (en) * | 2005-03-24 | 2006-09-28 | Renovis, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
| JP2009530304A (ja) * | 2006-03-16 | 2009-08-27 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
| JP2009530302A (ja) * | 2006-03-16 | 2009-08-27 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
| JP2009541206A (ja) * | 2006-03-16 | 2009-11-26 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
Family Cites Families (101)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US588736A (en) * | 1897-08-24 | Egg-tester | ||
| FR2450E (fr) | 1903-02-09 | 1904-04-07 | Sulzer Freres Soc | Palier pour pompes et autres machines analogues |
| DE2343984A1 (de) | 1973-08-31 | 1975-03-13 | Hoechst Ag | Wasserunloesliche disazomethinfarbstoffe, verfahren zu ihrer herstellung und ihre verwendung |
| US3950343A (en) | 1973-11-06 | 1976-04-13 | Ayerst, Mckenna And Harrison Ltd. | Pyrroloisoquinoline derivatives |
| US3900477A (en) | 1973-11-06 | 1975-08-19 | Ayerst Mckenna & Harrison | 5-amino-and 5-hydrazinodihydropyrroloisoquinoline derivatives |
| SU749832A1 (ru) | 1978-03-24 | 1980-07-23 | Предприятие П/Я М-5885 | Способ получени амино- -оксифенантридонов |
| GB2044254B (en) | 1979-01-26 | 1983-01-26 | Wyeth John & Brother Ltd | Piperidine derivatives |
| EP0093488A3 (en) | 1982-03-18 | 1984-05-23 | Beecham Group Plc | Nortropyl benzopyrrolinone compounds, process for their preparation and pharmaceutical compositions containing them |
| DE3368061D1 (en) | 1982-05-11 | 1987-01-15 | Beecham Group Plc | Azabicycloalkane derivatives, their preparation and medicaments containing them |
| EP0101641A3 (en) | 1982-07-22 | 1984-03-28 | Beecham Group Plc | Sulfonylamino-aza-bicyclo-alkyl derivatives |
| JPH0731405B2 (ja) | 1986-05-02 | 1995-04-10 | キヤノン株式会社 | 電子写真感光体 |
| JP2699511B2 (ja) | 1988-01-29 | 1998-01-19 | 武田薬品工業株式会社 | 置換アミン類 |
| US4897391A (en) | 1988-06-17 | 1990-01-30 | Schering Corporation | Tricyclic anti-allergy, antiinflammatory and anti-hyperproliferative compounds |
| US5776963A (en) | 1989-05-19 | 1998-07-07 | Hoechst Marion Roussel, Inc. | 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility |
| GB8926560D0 (en) | 1989-11-24 | 1990-01-17 | Zambeletti Spa L | Pharmaceuticals |
| US5140023A (en) | 1990-04-27 | 1992-08-18 | G. D. Searle & Co. | Azatetracycle compounds |
| HU213136B (en) | 1990-08-14 | 1997-02-28 | Kyorin Seiyaku Kk | Process for producing fluoroethyl camptothecin derivatives and pharmaceutical compositions containing them |
| KR920008026A (ko) | 1990-10-24 | 1992-05-27 | 오노 화아마슈티칼 캄파니 리미팃드 | 이소퀴놀리논 유도체 또는 이의 무독성 산부가염 또는 이의 수화물, 이의 제조방법 및 이를 포함하는 약제 조성물 |
| JPH04270273A (ja) | 1991-02-25 | 1992-09-25 | Kyorin Pharmaceut Co Ltd | チアゾリジン−２，４−ジオン誘導体とその塩及びその製造法 |
| EP0502575A1 (en) | 1991-03-06 | 1992-09-09 | Merck & Co. Inc. | Substituted 1-(2H)-isoquinolinones |
| AU1532492A (en) | 1991-04-18 | 1992-11-17 | Dr. Lo Zambeletti S.P.A. | Use of heterocyclic compounds for the treatment of inflammatory pain |
| US5491148A (en) | 1991-04-26 | 1996-02-13 | Syntex (U.S.A.) Inc. | Isoquinolinone and dihydroisoquinolinone 5-HT3 receptor antagonists |
| DE69209576T4 (de) | 1991-05-10 | 1997-01-30 | Takeda Chemical Industries Ltd | Pyridinderivate, deren Herstellung und Anwendung |
| GB9122859D0 (en) | 1991-10-28 | 1991-12-11 | Smithkline Beecham Plc | Novel compounds |
| US5272158A (en) | 1991-10-29 | 1993-12-21 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| JPH06295078A (ja) | 1992-04-24 | 1994-10-21 | Canon Inc | 電子写真感光体、該電子写真感光体を備えた電子写真装置並びにファクシミリ |
| US5840903A (en) | 1992-07-27 | 1998-11-24 | G. D. Searle & Co. | 4-aminomethyl-1-azaadamantane derived benzamides |
| US5354757A (en) | 1992-12-15 | 1994-10-11 | G. D. Searle & Co. | Azanoradamantanes |
| JPH08511538A (ja) | 1993-06-09 | 1996-12-03 | スミスクライン・ビーチャム・コーポレイション | 二環式フィブリノゲン拮抗物質 |
| DE4345266C2 (de) | 1993-10-04 | 1996-12-19 | Luitpold Pharma Gmbh | Heterocyclische Carbamate, Verfahren zu ihrer Herstellung und Arzneimittel |
| CA2155662A1 (en) | 1993-12-27 | 1995-07-06 | Fumihiro Ozaki | Anthranilic acid derivative |
| US5530018A (en) | 1994-02-04 | 1996-06-25 | G. D. Searle & Co. | Meso-azanoradamantanes |
| GB9409150D0 (en) | 1994-05-09 | 1994-06-29 | Black James Foundation | Cck and gastrin receptor ligands |
| US5500442A (en) | 1994-06-10 | 1996-03-19 | American Home Products Corporation | Cyclobut-3-ene-1,2-dione derivatives as smooth muscle relaxants |
| US5644144A (en) * | 1994-09-23 | 1997-07-01 | Advanced Micro Devices, Inc. | Device and method for programming a logic level within an integrated circuit using multiple mask layers |
| US5631280A (en) | 1995-03-29 | 1997-05-20 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| JP2000501063A (ja) | 1995-06-29 | 2000-02-02 | メルク エンド カンパニー インコーポレーテッド | ファルネシル−タンパク質トランスフェラーゼ阻害剤の組み合わせ |
| US5723411A (en) | 1995-10-31 | 1998-03-03 | E. I. Du Pont De Nemours And Company | Herbicidal pyridazinones |
| JP3285746B2 (ja) | 1995-11-24 | 2002-05-27 | 株式会社資生堂 | フェニレンジアミン誘導体及びラジカルスカベンジャー、脳梗塞抑制剤、脳浮腫抑制剤 |
| US5756518A (en) | 1996-04-02 | 1998-05-26 | Kowa Co., Ltd. | Phenylene derivatives |
| AU2980797A (en) | 1996-06-11 | 1998-01-07 | Yoshitomi Pharmaceutical Industries, Ltd. | Fused heterocyclic compounds and medicinal uses thereof |
| WO1998004247A1 (en) | 1996-07-25 | 1998-02-05 | Biogen, Inc. | Cell adhesion inhibitors |
| US6429212B1 (en) | 1996-08-16 | 2002-08-06 | Ishihara Sangyo Kaisha Ltd. | Medicinal composition |
| DE19650975A1 (de) | 1996-12-09 | 1998-06-10 | Basf Ag | Neue heterocyclisch substituierte Benzamide und deren Anwendung |
| DE19653645A1 (de) | 1996-12-20 | 1998-06-25 | Hoechst Ag | Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung |
| DE19653647A1 (de) | 1996-12-20 | 1998-06-25 | Hoechst Ag | Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung |
| US6262068B1 (en) | 1997-02-21 | 2001-07-17 | Bristol-Myers Squibb Company | Lactam derivatives as antiarrhythmic agents |
| PT877019E (pt) | 1997-05-09 | 2002-05-31 | Hoechst Ag | Acidos diaminocarboxilicos substituidos |
| TW544448B (en) | 1997-07-11 | 2003-08-01 | Novartis Ag | Pyridine derivatives |
| DK1023291T3 (da) | 1997-10-07 | 2004-10-04 | Ortho Mcneil Pharm Inc | Dipyridoimidazolderivater, som er egnet til behandling af lidelser i centralnervesystemet |
| CA2307030A1 (en) | 1997-10-24 | 1999-05-06 | Mervyn Thompson | Substituted isoquinoline derivatives and their use as anticonvulsants |
| JP3337992B2 (ja) | 1997-11-04 | 2002-10-28 | ファイザー製薬株式会社 | ５−置換ピコリン酸化合物及びその製造方法 |
| SE9704545D0 (sv) | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| SE9704546D0 (sv) | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| JPH11171774A (ja) | 1997-12-05 | 1999-06-29 | Kyowa Hakko Kogyo Co Ltd | 血球増多剤 |
| SE9704544D0 (sv) | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| AU1887999A (en) | 1998-01-29 | 1999-08-16 | Dr. Reddy's Research Foundation | Novel alkanoic acids and their use in medicine, process for their preparation and pharmaceutical compositions containing them |
| WO1999059975A1 (en) | 1998-05-15 | 1999-11-25 | Guilford Pharmaceuticals Inc. | Fused tricyclic compounds which inhibit parp activity |
| GB9817424D0 (en) | 1998-08-11 | 1998-10-07 | Smithkline Beecham Plc | Novel compounds |
| SE9901875D0 (sv) | 1999-05-25 | 1999-05-25 | Astra Pharma Prod | Novel compounds |
| GB9915995D0 (en) | 1999-07-09 | 1999-09-08 | Ahmed S | Non-steroidal sulphamate compounds for use as oestrone sulphatase inhibitors |
| JP2003506388A (ja) | 1999-08-04 | 2003-02-18 | アイカゲン インコーポレイテッド | 疼痛および不安症を処置または予防するための方法 |
| EP1208085B1 (en) | 1999-08-04 | 2007-12-05 | Icagen, Inc. | Benzanilides as potassium channel openers |
| GB9919411D0 (en) | 1999-08-18 | 1999-10-20 | Zeneca Ltd | Chemical compounds |
| AU7314200A (en) | 1999-09-17 | 2001-04-24 | Yamanouchi Pharmaceutical Co., Ltd. | Benzimidazole derivatives |
| JP2001172258A (ja) | 1999-12-17 | 2001-06-26 | Sumitomo Pharmaceut Co Ltd | 神経網膜変性疾患の治療薬 |
| SE9904652D0 (sv) | 1999-12-17 | 1999-12-17 | Astra Pharma Prod | Novel Compounds |
| AU2001239725A1 (en) | 2000-01-13 | 2001-07-24 | Tularik, Inc. | Antibacterial agents |
| GB0005366D0 (en) | 2000-03-06 | 2000-04-26 | Xenova Ltd | Pharmaceutical compounds |
| US6469026B2 (en) | 2000-03-24 | 2002-10-22 | Millennium Pharmaceuticals, Inc. | Isoquinolone inhibitors of factor Xa |
| WO2002006240A1 (en) | 2000-07-13 | 2002-01-24 | Guilford Pharmaceuticals Inc. | Substituted 4,9-dihydrocyclopenta[imn] phenanthridine-5-ones, derivatives thereof and their uses |
| US6603013B2 (en) | 2000-07-17 | 2003-08-05 | Merck & Co., Inc. | Heterogeneously catalyzed process for cross coupling alkenyl halides with boronic acids |
| US20040122223A1 (en) | 2001-02-07 | 2004-06-24 | Davis Jeremy Martin | Non-natural nucleotides and dinucleotides |
| JP2002338837A (ja) | 2001-05-16 | 2002-11-27 | Fuji Photo Film Co Ltd | 新規化合物、色素、インク組成物、インクジェット用インク、インクジェット記録方法、及び熱転写色素 |
| WO2002094790A1 (en) | 2001-05-23 | 2002-11-28 | Mitsubishi Pharma Corporation | Fused heterocyclic compound and medicinal use thereof |
| CA2455181C (en) | 2001-08-01 | 2010-04-06 | Merck & Co., Inc. | Benzimidazo[4,5-f]isoquinolinone derivatives |
| US7074805B2 (en) | 2002-02-20 | 2006-07-11 | Abbott Laboratories | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
| CA2476936A1 (en) | 2002-02-20 | 2003-08-28 | Chih-Hung Lee | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (vr1) receptor |
| GB0206876D0 (en) | 2002-03-22 | 2002-05-01 | Merck Sharp & Dohme | Therapeutic agents |
| AU2003219088A1 (en) | 2002-03-26 | 2003-10-08 | Zentopharm Gmbh | Fredericamycin derivatives |
| DE10215316C1 (de) | 2002-04-02 | 2003-12-18 | Schering Ag | Chinolin- und Isochinolin-Derivate, ein pharmazeutisches Mittel und ihre Verwendung als Entzündungshemmer |
| RS95404A (sr) | 2002-05-03 | 2006-10-27 | Schering Aktiengesellschaft | Tiazolidinoni i njihova primena kao inhibitora polo like kinaze |
| AU2003281623B8 (en) | 2002-07-22 | 2009-06-11 | Asahi Kasei Pharma Corporation | 5-substituted isoquinoline derivative |
| DE10238865A1 (de) | 2002-08-24 | 2004-03-11 | Boehringer Ingelheim International Gmbh | Neue Carbonsäureamid-Verbindungen mit MCH-antagonistischer Wirkung, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| JP2004203813A (ja) | 2002-12-26 | 2004-07-22 | Tokuyama Corp | クロメン化合物 |
| PA8591801A1 (es) | 2002-12-31 | 2004-07-26 | Pfizer Prod Inc | Inhibidores benzamidicos del receptor p2x7. |
| SG2012000667A (en) | 2003-01-08 | 2015-03-30 | Univ Washington | Antibacterial agents |
| TW200503994A (en) | 2003-01-24 | 2005-02-01 | Novartis Ag | Organic compounds |
| CA2514940A1 (en) | 2003-02-03 | 2004-08-19 | Janssen Pharmaceutica N.V. | Quinoline-derived amide modulators of vanilloid vr1 receptor |
| US20060211724A1 (en) | 2003-04-28 | 2006-09-21 | Verschueren Gaston W | Hiv integrase inhibitors |
| JP4731468B2 (ja) | 2003-05-12 | 2011-07-27 | ファイザー・プロダクツ・インク | Ｐ２ｘ７受容体のベンズアミド阻害剤 |
| CN1566099A (zh) | 2003-06-13 | 2005-01-19 | 中国科学院上海药物研究所 | 异喹啉－1,3,4－三酮类化合物、制备方法及其用途 |
| WO2004113345A1 (ja) | 2003-06-20 | 2004-12-29 | Japan Tobacco Inc. | 縮合ピロール化合物及びその医薬用途 |
| US7390820B2 (en) | 2003-08-25 | 2008-06-24 | Amgen Inc. | Substituted quinolinone derivatives and methods of use |
| JP4667384B2 (ja) | 2003-10-07 | 2011-04-13 | レノビス， インコーポレイテッド | イオンチャネルリガンドとしてのアミド誘導体および薬学的組成物、ならびにこれらを使用する方法 |
| US7491794B2 (en) | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| TW200530235A (en) | 2003-12-24 | 2005-09-16 | Renovis Inc | Bicycloheteroarylamine compounds as ion channel ligands and uses thereof |
| JP2005232175A (ja) | 2004-01-21 | 2005-09-02 | Asahi Kasei Pharma Kk | ５−置換イソキノリン医薬 |
| EP1737414A2 (en) | 2004-01-23 | 2007-01-03 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments of inflammatory and neuropatic pain |
| US7576099B2 (en) | 2005-02-28 | 2009-08-18 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
| WO2007109154A2 (en) * | 2006-03-16 | 2007-09-27 | Renovis, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
-
2008
- 2008-03-07 DK DK08726672.2T patent/DK2124562T3/en active
- 2008-03-07 ES ES08726672.2T patent/ES2576643T3/es active Active
- 2008-03-07 EP EP08726672.2A patent/EP2124562B1/en not_active Not-in-force
- 2008-03-07 WO PCT/US2008/003175 patent/WO2008112205A1/en not_active Ceased
- 2008-03-07 US US12/075,111 patent/US8093265B2/en not_active Expired - Fee Related
- 2008-03-07 CA CA2680275A patent/CA2680275C/en not_active Expired - Fee Related
- 2008-03-07 JP JP2009552762A patent/JP2010520875A/ja active Pending
- 2008-03-07 CN CN200880014110.6A patent/CN101686680B/zh active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006102588A1 (en) * | 2005-03-24 | 2006-09-28 | Renovis, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
| WO2006102610A2 (en) * | 2005-03-24 | 2006-09-28 | Renovis, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
| JP2009530304A (ja) * | 2006-03-16 | 2009-08-27 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
| JP2009530302A (ja) * | 2006-03-16 | 2009-08-27 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
| JP2009541206A (ja) * | 2006-03-16 | 2009-11-26 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009530304A (ja) * | 2006-03-16 | 2009-08-27 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
| JP2009542595A (ja) * | 2006-07-06 | 2009-12-03 | グラクソ グループ リミテッド | Ｐ２ｘ７受容体アンタゴニストとしての置換ｎ−フェニルメチル−５−オキソ−プロリン−２−アミドおよびそれらの使用方法 |
| JP2014520880A (ja) * | 2011-07-22 | 2014-08-25 | アクテリオン ファーマシューティカルズ リミテッド | Ｐ２ｘ７受容体アンタゴニストとしての複素環アミド誘導体 |
| JP2017520538A (ja) * | 2014-06-05 | 2017-07-27 | 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Ｍｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | 新規キノリン誘導体及び神経変性疾患におけるそれらの使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2576643T3 (es) | 2016-07-08 |
| EP2124562A4 (en) | 2010-03-10 |
| CA2680275A1 (en) | 2008-09-18 |
| EP2124562B1 (en) | 2016-04-20 |
| WO2008112205A1 (en) | 2008-09-18 |
| CN101686680A (zh) | 2010-03-31 |
| DK2124562T3 (en) | 2016-08-01 |
| HK1136967A1 (zh) | 2010-07-16 |
| CN101686680B (zh) | 2015-12-09 |
| US8093265B2 (en) | 2012-01-10 |
| EP2124562A1 (en) | 2009-12-02 |
| US20080287415A1 (en) | 2008-11-20 |
| CA2680275C (en) | 2016-08-23 |
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