CA2825204C - Pyrrolopyrazine-spirocyclic piperidine amides as modulators of ion channels - Google Patents
Pyrrolopyrazine-spirocyclic piperidine amides as modulators of ion channels Download PDFInfo
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- CA2825204C CA2825204C CA2825204A CA2825204A CA2825204C CA 2825204 C CA2825204 C CA 2825204C CA 2825204 A CA2825204 A CA 2825204A CA 2825204 A CA2825204 A CA 2825204A CA 2825204 C CA2825204 C CA 2825204C
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- Prior art keywords
- pain
- compound
- pharmaceutically acceptable
- acceptable salt
- alkyl
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/12—Antihypertensives
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
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| US201161438685P | 2011-02-02 | 2011-02-02 | |
| US61/438,685 | 2011-02-02 | ||
| US201161440987P | 2011-02-09 | 2011-02-09 | |
| US61/440,987 | 2011-02-09 | ||
| US201161495538P | 2011-06-10 | 2011-06-10 | |
| US61/495,538 | 2011-06-10 | ||
| PCT/US2012/023593 WO2012106499A1 (en) | 2011-02-02 | 2012-02-02 | Pyrrolopyrazine-spirocyclic piperidine amides as modulators of ion channels |
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| CA2825204A1 CA2825204A1 (en) | 2012-08-09 |
| CA2825204C true CA2825204C (en) | 2019-06-11 |
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| CA2825204A Active CA2825204C (en) | 2011-02-02 | 2012-02-02 | Pyrrolopyrazine-spirocyclic piperidine amides as modulators of ion channels |
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Families Citing this family (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101827593B (zh) | 2007-08-24 | 2013-07-24 | 沃泰克斯药物股份有限公司 | 用于治疗(特别是)囊性纤维化的异噻唑并吡啶酮 |
| EP2595989B1 (en) | 2010-05-06 | 2016-07-13 | Vertex Pharmaceuticals Incorporated | Heterocyclic chromene-spirocyclic piperidine amides as modulators of ion channels |
| PL2670752T3 (pl) * | 2011-02-02 | 2016-09-30 | Pirolopirazynowe spirocykliczne piperydynoamidy jako modulatory kanałów jonowych | |
| MX2013009393A (es) | 2011-02-18 | 2013-08-29 | Vertex Pharma | Piperidinamidas cromano-espirociclicas como moduladores de canales de iones. |
| ES2618929T3 (es) | 2011-03-14 | 2017-06-22 | Vertex Pharmaceuticals Incorporated | Morfolina-Spiro piperidina amida cíclica como moduladores del canal iónico |
| EP2773637B1 (en) | 2011-10-31 | 2016-06-08 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
| CN104093716B (zh) | 2011-10-31 | 2017-06-23 | 克赛农制药股份有限公司 | 联芳醚磺酰胺化合物及其作为治疗剂的用途 |
| CA2874621A1 (en) | 2012-05-22 | 2013-11-28 | Genentech, Inc. | N-substituted benzamides and their use in the treatment of pain |
| BR112015000187A2 (pt) | 2012-07-06 | 2017-06-27 | Genentech Inc | benzamidas substituídas com n e métodos de uso das mesmas |
| WO2014022639A1 (en) * | 2012-08-01 | 2014-02-06 | Vertex Pharmaceuticals Incorporated | Solid forms of (4-isopropoxy-3-methoxyphenyl)(2'-methyl-6'-(trifluoromethyl)-3',4'-dihydro-2'h-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-yl)methanone |
| AR094667A1 (es) | 2013-01-31 | 2015-08-19 | Vertex Pharma | Piridonamidas como moduladores de canales de sodio |
| AR095192A1 (es) | 2013-01-31 | 2015-09-30 | Vertex Pharma | Quinolina y quinazolinamidas como modulares de canales de sodio |
| WO2014134391A1 (en) | 2013-02-28 | 2014-09-04 | Bristol-Myers Squibb Company | Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors |
| TW201444798A (zh) | 2013-02-28 | 2014-12-01 | 必治妥美雅史谷比公司 | 作爲強效ｒｏｃｋ１及ｒｏｃｋ２抑制劑之苯基吡唑衍生物 |
| WO2014153037A1 (en) | 2013-03-14 | 2014-09-25 | Genentech, Inc. | Substituted triazolopyridines and methods of use thereof |
| US9493429B2 (en) | 2013-03-15 | 2016-11-15 | Genentech, Inc. | Substituted benzoxazoles and methods of use thereof |
| CA2917198C (en) * | 2013-07-10 | 2022-06-07 | Vertex Pharmaceuticals Incorporated | Fused piperidine amides as modulators of ion channels |
| CA2918365C (en) | 2013-07-19 | 2021-09-07 | Vertex Pharmaceuticals Incorporated | Sulfonamides as modulators of sodium channels |
| MX2016006936A (es) | 2013-11-27 | 2016-10-05 | Genentech Inc | Benzamidas sustituidas y metodos para usarlas. |
| UA121379C2 (uk) | 2013-12-13 | 2020-05-25 | Вертекс Фармасьютикалз Інкорпорейтед | Проліки піридонамідів, застосовувані як модулятори натрієвих каналів |
| CN106715418A (zh) | 2014-07-07 | 2017-05-24 | 基因泰克公司 | 治疗化合物及其使用方法 |
| BR112017024853A2 (pt) | 2015-05-22 | 2018-08-07 | Genentech Inc | composto, composição farmacêutica, método para tratar uma doença ou condição em um mamífero, para tratamento de prurido em um mamífero, para tratamento ou profilaxia e uso de um composto |
| JP2018526371A (ja) | 2015-08-27 | 2018-09-13 | ジェネンテック， インコーポレイテッド | 治療化合物及びその使用方法 |
| BR112018006189A2 (pt) | 2015-09-28 | 2018-10-09 | Genentech Inc | compostos da fórmula, composição farmacêutica, métodos de tratamento de uma doença, de diminuição do fluxo de íons e de tratamento de prurido em um mamífero, método para tratamento de dores em um mamífero e uso de um composto |
| CN108495851A (zh) | 2015-11-25 | 2018-09-04 | 基因泰克公司 | 取代的苯甲酰胺及其使用方法 |
| WO2017172802A1 (en) | 2016-03-30 | 2017-10-05 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
| MA46546A (fr) | 2016-10-17 | 2021-05-05 | Genentech Inc | Composés thérapeutiques et leurs procédés d'utilisation |
| CN106749330A (zh) * | 2016-12-29 | 2017-05-31 | 长春海谱润斯科技有限公司 | 一种杂环衍生物及使用该杂环衍生物的有机发光器件 |
| JP2020511511A (ja) | 2017-03-24 | 2020-04-16 | ジェネンテック， インコーポレイテッド | ナトリウムチャネル阻害剤としての４−ピペリジン−ｎ−（ピリミジン−４−イル）クロマン−７−スルホンアミド誘導体 |
| JP7104070B2 (ja) | 2017-05-16 | 2022-07-20 | 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 | ナトリウムチャネルの調節因子としての重水素化ピリドンアミドおよびそのプロドラッグ |
| ES3008911T3 (en) | 2017-07-11 | 2025-03-25 | Vertex Pharma | Carboxamides as modulators of sodium channels |
| US20190343817A1 (en) | 2018-02-12 | 2019-11-14 | Vertex Pharmaceuticals Incorporated | Method of treating pain |
| JP2021514980A (ja) | 2018-02-26 | 2021-06-17 | ジェネンテック， インコーポレイテッド | 疼痛及び関連病態に対するピリジン−スルホンアミド化合物及びその使用 |
| JP2021519788A (ja) | 2018-03-30 | 2021-08-12 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | ナトリウムチャネル阻害剤としての縮合環ヒドロピリド化合物 |
| TW202003490A (zh) | 2018-05-22 | 2020-01-16 | 瑞士商赫孚孟拉羅股份公司 | 治療性化合物及其使用方法 |
| CN112689629B (zh) | 2018-07-09 | 2024-04-23 | 利伯研究所公司 | 用于抑制Nav1.8的哒嗪化合物 |
| CA3105657A1 (en) | 2018-07-09 | 2020-01-16 | Lieber Institute, Inc. | Pyridine carboxamide compounds for inhibiting nav1.8 |
| AU2019360941B2 (en) * | 2018-10-15 | 2025-02-27 | Takeda Pharmaceutical Company Limited | TYK2 inhibitors and uses thereof |
| US12441703B2 (en) | 2019-01-10 | 2025-10-14 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
| WO2020146612A1 (en) | 2019-01-10 | 2020-07-16 | Vertex Pharmaceuticals Incorporated | Esters and carbamates as modulators of sodium channels |
| WO2020176763A1 (en) | 2019-02-27 | 2020-09-03 | Vertex Pharmaceuticals Incorporated | Dosage form comprising prodrug of na 1.8 sodium channel inhibitor |
| US10828287B2 (en) | 2019-03-11 | 2020-11-10 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| EP3937929A4 (en) * | 2019-03-11 | 2022-12-28 | Nocion Therapeutics, Inc. | CHARGED ION CHANNEL BLOCKERS AND METHODS OF USE |
| WO2020185881A1 (en) | 2019-03-11 | 2020-09-17 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| CN113924094A (zh) | 2019-03-11 | 2022-01-11 | 诺西恩医疗公司 | 酯取代的离子通道阻滞剂及其使用方法 |
| WO2020219867A1 (en) | 2019-04-25 | 2020-10-29 | Vertex Pharmaceuticals Incorporated | Pyridone amide co-crystal compositions for the treatment of pain |
| BR112022008575A2 (pt) | 2019-11-06 | 2022-08-09 | Nocion Therapeutics Inc | Bloqueadores de canal iônico carregado e métodos para uso |
| EP4054586A4 (en) | 2019-11-06 | 2023-11-22 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| SI4069691T1 (sl) | 2019-12-06 | 2025-02-28 | Vertex Pharmaceuticals Incorporated | Substituirani tetrahidrofurani kot modulatorji natrijevih kanalčkov |
| KR20230022830A (ko) | 2020-03-11 | 2023-02-16 | 녹시온 테라퓨틱스 인코포레이티드 | 하전된 이온 채널 차단제 및 사용 방법 |
| US12162851B2 (en) | 2020-03-11 | 2024-12-10 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| JP2024520648A (ja) | 2021-06-04 | 2024-05-24 | 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 | ナトリウムチャネルの調節因子としての置換テトラヒドロフラン－２－カルボキサミド |
| EP4347031B1 (en) | 2021-06-04 | 2025-10-29 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamides as modulators of sodium channels |
| CA3221960A1 (en) | 2021-06-04 | 2022-12-08 | Vertex Pharmaceuticals Incorporated | Hydroxy and (halo)alkoxy substituted tetrahydrofurans as modulators of sodium channels |
| CN117794918A (zh) | 2021-06-04 | 2024-03-29 | 沃泰克斯药物股份有限公司 | 经取代的四氢呋喃类似物作为钠通道调节剂 |
| US20240285596A1 (en) | 2021-06-04 | 2024-08-29 | Vertex Pharmaceuticals Incorporated | Solid dosage forms and dosing regimens comprising (2r,3s,4s,5r)-4-[[3-(3,4-difluoro-2-methoxy-phenyl)-4,5-dimethyl-5-(trifluoromethyl) tetrahydrofuran-2-carbonyl]amino]pyridine-2-carboxamide |
| WO2022256679A1 (en) | 2021-06-04 | 2022-12-08 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamide analogs as modulators of sodium channels |
| CR20240513A (es) | 2022-04-22 | 2025-04-30 | Vertex Pharma | Compuestos de heteroarilo para el tratamiento del dolor |
| CN119487003A (zh) | 2022-04-22 | 2025-02-18 | 沃泰克斯药物股份有限公司 | 用于治疗疼痛的杂芳基化合物 |
| AU2023257313A1 (en) | 2022-04-22 | 2024-10-31 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| EP4511114A1 (en) | 2022-04-22 | 2025-02-26 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| EP4630405A1 (en) | 2022-12-06 | 2025-10-15 | Vertex Pharmaceuticals Incorporated | Process for the synthesis of substituted tetrahydrofuran modulators of sodium channels |
| CN117385378B (zh) * | 2023-10-13 | 2024-09-24 | 厦门大学 | 一种缺电子芳香缩醛的电氧化制备方法和应用 |
| WO2025090516A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing compounds for treating pain and solid forms thereof |
| WO2025090480A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| TW202535867A (zh) | 2023-10-23 | 2025-09-16 | 美商維泰克斯製藥公司 | 用於治療疼痛之鈉通道調節劑及其固體形式的製備方法 |
| TW202523313A (zh) | 2023-10-23 | 2025-06-16 | 美商維泰克斯製藥公司 | 用於治療疼痛之雜芳基化合物 |
| US20250186419A1 (en) | 2023-12-07 | 2025-06-12 | Vertex Pharmaceuticals Incorporated | Dosing regimens for treating pain |
| CN121013715A (zh) * | 2024-03-22 | 2025-11-25 | 艾瑞克·奎因 | 镁和利多卡因组合物 |
Family Cites Families (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3939159A (en) | 1974-05-29 | 1976-02-17 | American Hoechst Corporation | Spiro(pyrrolo (1,2-A)quinoxalines) |
| PT67194B (en) | 1976-11-02 | 1979-03-23 | Lilly Co Eli | Process for preparing 4a-aryl-octahydro-1h-2-pyrindines |
| BG30927A3 (bg) | 1977-12-27 | 1981-09-15 | Eli Lilly And Company | Метод за получаване на транс-4-алфа-фенил-октахидро-1н-2 пиридини |
| US4353901A (en) | 1981-10-19 | 1982-10-12 | Syntex (U.S.A.) Inc. | 9-(1,4-Benzodioxan-2-ylalkyl and hydroxyalkyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-ones |
| GB8827479D0 (en) | 1988-11-24 | 1988-12-29 | Zambeletti Spa L | Novel compounds |
| IL96507A0 (en) | 1989-12-08 | 1991-08-16 | Merck & Co Inc | Nitrogen-containing spirocycles and pharmaceutical compositions containing them |
| US5206240A (en) | 1989-12-08 | 1993-04-27 | Merck & Co., Inc. | Nitrogen-containing spirocycles |
| US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| JPH04297458A (ja) | 1991-03-27 | 1992-10-21 | Toray Ind Inc | イソキノリン誘導体およびその製造方法 |
| GB9104656D0 (en) | 1991-03-05 | 1991-04-17 | Zambeletti Spa L | Pharmaceuticals |
| US5886026A (en) | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
| DE4341403A1 (de) | 1993-12-04 | 1995-06-08 | Basf Ag | N-substituierte 3-Azabicycloalkan-Derivate, ihre Herstellung und Verwendung |
| EP0758313A4 (en) | 1994-05-06 | 1999-09-15 | Pharmacopeia Inc | COMBINATORIAL LIBRARY OF DIHYDROBENZOPYRANES |
| US6017768A (en) | 1994-05-06 | 2000-01-25 | Pharmacopeia, Inc. | Combinatorial dihydrobenzopyran library |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| IT1276462B1 (it) | 1995-07-03 | 1997-10-31 | Rotta Research Lab | Diamidi aromatiche acide ad attivita' antigastrinica, procedimento per la loro preparazione e loro uso farmaceutico |
| JPH11512723A (ja) | 1995-09-29 | 1999-11-02 | イーライ リリー アンド カンパニー | フィブリノゲン依存血小板凝集抑制物質としてのスピロ化合物 |
| AP2001002356A0 (en) * | 1999-06-07 | 2001-12-31 | Warner Lambert Co | Tricyclic analgesics. |
| US20040266802A1 (en) * | 1999-06-07 | 2004-12-30 | Alain Calvet | Tricyclic analgesics |
| US20020151712A1 (en) | 1999-09-14 | 2002-10-17 | Nan-Horng Lin | 3-pyrrolidinyloxy-3'-pyridyl ether compounds useful for controlling chemical synaptic transmission |
| WO2002020509A2 (de) | 2000-09-06 | 2002-03-14 | Bayer Aktiengesellschaft | Arzneimittel gegen virale erkrankungen |
| US20040014744A1 (en) | 2002-04-05 | 2004-01-22 | Fortuna Haviv | Substituted pyridines having antiangiogenic activity |
| JPWO2003095427A1 (ja) | 2002-05-10 | 2005-09-15 | 大正製薬株式会社 | スピロ環化合物 |
| EP1533314A4 (en) | 2002-06-11 | 2006-08-02 | Sankyo Co | PROCESS FOR THE PREPARATION OF CYCLIC THIOETHERES, AND SYNTHETIC INTERMEDIATE DAF R |
| AU2003274053A1 (en) | 2002-10-22 | 2004-05-13 | Glaxo Group Limited | Aryloxyalkylamine derivates as h3 receptor ligands |
| CN1729196A (zh) | 2002-10-24 | 2006-02-01 | 三共株式会社 | 旋光亚砜的制备方法 |
| BR0317230A (pt) | 2002-12-13 | 2005-10-25 | Smithkline Beecham Corp | Composto, composição, métodos de antagonizar uma atividade do receptor de quimiocina ccr-5, e de tratar uma infecção viral em um paciente, e, uso de um composto |
| EP1599447A1 (en) | 2003-02-28 | 2005-11-30 | Galderma Research & Development, S.N.C. | Ligands that modulate lxr-type receptors |
| WO2004092179A1 (ja) | 2003-04-14 | 2004-10-28 | Nippon Soda Co. Ltd. | スピロ誘導体、製造法および抗酸化薬 |
| FR2856685B1 (fr) | 2003-06-25 | 2005-09-23 | Merck Sante Sas | Derives de thiazolylpiperidine, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent |
| CN101921279A (zh) | 2003-10-01 | 2010-12-22 | 阿得罗公司 | 螺环杂环衍生物及其应用方法 |
| JPWO2005037269A1 (ja) | 2003-10-21 | 2006-12-28 | 住友製薬株式会社 | 新規ピペリジン誘導体 |
| TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| WO2005121090A1 (en) | 2004-06-02 | 2005-12-22 | Abbott Laboratories | Substituted piperidines that have antiangiogenic activity |
| US7598261B2 (en) | 2005-03-31 | 2009-10-06 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
| JP2008540395A (ja) | 2005-05-03 | 2008-11-20 | ファイザー・インク | アミドレソルシノール化合物 |
| WO2007050124A1 (en) | 2005-05-19 | 2007-05-03 | Xenon Pharmaceuticals Inc. | Fused piperidine derivatives and their uses as therapeutic agents |
| BRPI0613427A2 (pt) | 2005-07-19 | 2012-10-30 | Merck & Co Inc | composto ou seu sal ou éster, composição farmacêutica, agente terapêutico, e , uso do composto ou seu sal ou éster |
| US20070066584A1 (en) | 2005-09-21 | 2007-03-22 | Wenqing Yao | Amido compounds and their use as pharmaceuticals |
| JP5217438B2 (ja) | 2005-11-18 | 2013-06-19 | 小野薬品工業株式会社 | 塩基性基を含有する化合物およびその用途 |
| CN101360750A (zh) * | 2005-11-23 | 2009-02-04 | 英特芒尼公司 | 应激活化蛋白激酶系统的调节方法 |
| AR057579A1 (es) | 2005-11-23 | 2007-12-05 | Merck & Co Inc | Compuestos espirociclicos como inhibidores de histona de acetilasa (hdac) |
| WO2007124045A2 (en) | 2006-04-20 | 2007-11-01 | Ampla Pharmaceuticals, Inc. | Piperidine and piperazine compounds for use in the treatment of obesity, eating disorders and sexual dysfunction by potentiation of mc4 receptor activity |
| JP2009536175A (ja) | 2006-05-05 | 2009-10-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 特定の細胞サイクル酵素の阻害剤としてのスピロ−（ｔｈｏ）ベンゾピラン−２，４’−ピペリジン−及びシクロヘキサン誘導体 |
| JP5257068B2 (ja) | 2006-05-16 | 2013-08-07 | 小野薬品工業株式会社 | 保護されていてもよい酸性基を含有する化合物およびその用途 |
| AU2007254359A1 (en) | 2006-05-18 | 2007-11-29 | Merck Sharp & Dohme Corp. | Aryl-fused spirocyclic compounds |
| US20090325992A1 (en) | 2006-07-31 | 2009-12-31 | Ono Pharmaceutical Co., Ltd. | Compound having cyclic group bound thereto through spiro binding and use thereof |
| EP2399577A1 (en) | 2006-09-12 | 2011-12-28 | Adolor Corporation | Use of N-containing spirocompounds for the enhancement of cognitive function |
| US20100210633A1 (en) | 2006-10-12 | 2010-08-19 | Epix Delaware, Inc. | Carboxamide compounds and their use |
| ATE552262T1 (de) | 2006-11-29 | 2012-04-15 | Pfizer Prod Inc | Spiroketone als inhibitoren von acetyl-coa- carboxylase |
| EP2125726B1 (en) * | 2006-12-22 | 2011-07-27 | F. Hoffmann-La Roche AG | Spiro-piperidine derivatives |
| US8138197B2 (en) | 2007-01-12 | 2012-03-20 | Msd K.K. | Spirochromanon derivatives |
| PE20081559A1 (es) | 2007-01-12 | 2008-11-20 | Merck & Co Inc | DERIVADOS DE ESPIROCROMANONA SUSTITUIDOS COMO INHIBIDORES DE ACETIL CoA CARBOXILASA |
| US20100113418A1 (en) | 2007-02-20 | 2010-05-06 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| EP2110377A1 (en) | 2008-04-15 | 2009-10-21 | DAC S.r.l. | Spirocyclic derivatives as histone deacetylase inhibitors |
| WO2009144554A1 (en) | 2008-05-28 | 2009-12-03 | Pfizer, Inc. | Pyrazolospiroketone acetyl-c0a carboxylase inhibitors |
| JP5501256B2 (ja) | 2008-07-04 | 2014-05-21 | Ｍｓｄ株式会社 | 新規スピロクロマノンカルボン酸 |
| MX2011000664A (es) | 2008-07-16 | 2011-02-24 | Schering Corp | Derivados biciclicos heterociclicos y uso de los mismos como moduladores de gpr119. |
| US20110166124A1 (en) | 2008-07-23 | 2011-07-07 | Mccormick Kevin D | Tricyclic spirocycle derivatives and methods of use |
| AU2009308769B2 (en) | 2008-10-31 | 2015-03-12 | Pain Therapeutics, Inc. | Filamin A-binding anti-inflammatory analgesic |
| WO2010051497A1 (en) | 2008-10-31 | 2010-05-06 | Pain Therapeutics, Inc. | Filamin a binding anti-inflammatory and analgesic |
| WO2010114957A1 (en) | 2009-04-03 | 2010-10-07 | Schering Corporation | Bicyclic piperidine and piperazine derivatives as gpcr modulators for the treatment of obesity, diabetes and other metabolic disorders |
| WO2010151595A1 (en) * | 2009-06-26 | 2010-12-29 | Schering Corporation | Pyrrolo-benzo-1,4-diazines useful as sodium channel blockers |
| US8354403B2 (en) | 2009-08-27 | 2013-01-15 | Merck Sharp & Dohme Corp. | Pyrrolidine derived beta 3 adrenergic receptor agonists |
| US8633183B2 (en) | 2010-01-26 | 2014-01-21 | Boehringer Ingelheim International Gmbh | 5-alkynyl-pyrimidines |
| EP2595989B1 (en) | 2010-05-06 | 2016-07-13 | Vertex Pharmaceuticals Incorporated | Heterocyclic chromene-spirocyclic piperidine amides as modulators of ion channels |
| PL2670752T3 (pl) * | 2011-02-02 | 2016-09-30 | Pirolopirazynowe spirocykliczne piperydynoamidy jako modulatory kanałów jonowych | |
| MX2013009393A (es) | 2011-02-18 | 2013-08-29 | Vertex Pharma | Piperidinamidas cromano-espirociclicas como moduladores de canales de iones. |
| ES2618929T3 (es) | 2011-03-14 | 2017-06-22 | Vertex Pharmaceuticals Incorporated | Morfolina-Spiro piperidina amida cíclica como moduladores del canal iónico |
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