CA2699382C - Modulators of cystic fibrosis transmembrane conductance regulator - Google Patents
Modulators of cystic fibrosis transmembrane conductance regulator Download PDFInfo
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- CA2699382C CA2699382C CA2699382A CA2699382A CA2699382C CA 2699382 C CA2699382 C CA 2699382C CA 2699382 A CA2699382 A CA 2699382A CA 2699382 A CA2699382 A CA 2699382A CA 2699382 C CA2699382 C CA 2699382C
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- optionally substituted
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- pharmaceutically acceptable
- tautomer
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Landscapes
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Applications Claiming Priority (3)
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| US97259907P | 2007-09-14 | 2007-09-14 | |
| US60/972,599 | 2007-09-14 | ||
| PCT/US2008/076376 WO2009036412A1 (en) | 2007-09-14 | 2008-09-15 | Modulators of cystic fibrosis transmembrane conductance regulator |
Publications (2)
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| CA2699382A1 CA2699382A1 (en) | 2009-03-19 |
| CA2699382C true CA2699382C (en) | 2016-05-10 |
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| CA2699382A Active CA2699382C (en) | 2007-09-14 | 2008-09-15 | Modulators of cystic fibrosis transmembrane conductance regulator |
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| NZ (1) | NZ583878A (enExample) |
| WO (1) | WO2009036412A1 (enExample) |
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| KR20060088537A (ko) | 2003-09-06 | 2006-08-04 | 버텍스 파마슈티칼스 인코포레이티드 | Ａｔｐ-결합 카세트 수송체의 조절자 |
| WO2005049018A1 (en) * | 2003-11-14 | 2005-06-02 | Vertex Pharmaceuticals Incorporated | Thiazoles and oxazoles useful as modulators of atp-binding cassette transporters |
| US7977322B2 (en) | 2004-08-20 | 2011-07-12 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| PL2489659T3 (pl) * | 2004-06-24 | 2018-06-29 | Vertex Pharma | Modulatory transporterów posiadających kasetę wiążącą atp |
| JP5143738B2 (ja) | 2005-08-11 | 2013-02-13 | 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 | 嚢胞性線維症膜コンダクタンス制御因子の調節物質 |
| DK1945632T3 (da) * | 2005-11-08 | 2013-12-16 | Vertex Pharma | Heterocycliske modulatorer af ATP-bindende kassettetransportører |
| PL1993360T3 (pl) | 2005-12-28 | 2017-08-31 | Vertex Pharmaceuticals Incorporated | Stałe postacie n-[2,4-bis(1,1-dimetyloetylo)-5-hydroksyfenylo]-1,4- dihydro-4-oksochinolino-3-karboksyamidu |
| EP2016065B1 (en) | 2005-12-28 | 2012-09-19 | Vertex Pharmaceuticals Incorporated | 1-(benzo[d][1,3]dioxol-5-yl)-n-(phenyl)cyclopropane-carboxamide derivatives and related compounds as modulators of atp-binding cassette transporters for the treatment of cystic fibrosis |
| US7671221B2 (en) * | 2005-12-28 | 2010-03-02 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding Cassette transporters |
| USRE50453E1 (en) | 2006-04-07 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US10022352B2 (en) | 2006-04-07 | 2018-07-17 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| US7645789B2 (en) | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| PL2674428T3 (pl) | 2006-04-07 | 2017-01-31 | Vertex Pharmaceuticals Incorporated | Modulatory transporterów z kasetą wiążącą ATP |
| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| CA2686838C (en) | 2007-05-09 | 2017-03-14 | Vertex Pharmaceuticals Incorporated | Modulators of cftr |
| JP5389030B2 (ja) | 2007-08-24 | 2014-01-15 | 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 | （特に）嚢胞性線維症の処置に有用なイソチアゾロピリジノン |
| DK2578571T3 (en) * | 2007-11-16 | 2015-10-05 | Vertex Pharma | Isoquinoline modulators of ATP binding cassette transporters |
| US20100036130A1 (en) | 2007-12-07 | 2010-02-11 | Vertex Pharmaceuticals Incorporated | Processes for producing cycloalkylcarboxamido-pyridine benzoic acids |
| LT3170818T (lt) | 2007-12-07 | 2020-05-25 | Vertex Pharmaceuticals Incorporated | Kietos 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioksol-5-il)ciklopropankarboksamido)-3-metilpiridin-2-il)benzoinės rūgšties formos |
| DK2639222T3 (en) * | 2007-12-07 | 2016-10-03 | Vertex Pharma | Methods for preparing cycloalkylcarboxamido-pyridinbenzoesyrer |
| CN101998854A (zh) * | 2007-12-07 | 2011-03-30 | 沃泰克斯药物股份有限公司 | 3-(6-(1-(2,2-二氟苯并[d][1,3]间二氧杂环戊烯-5-基)环丙烷甲酰氨基)-3-甲基吡啶-2-基)苯甲酸的制剂 |
| WO2009108657A2 (en) * | 2008-02-28 | 2009-09-03 | Vertex Pharmaceuticals Incorporated | Heteroaryl derivatives as cftr modulators |
| AU2009231993B2 (en) | 2008-03-31 | 2013-10-10 | Vertex Pharmaceuticals Incorporated | Pyridyl derivatives as CFTR modulators |
| US12458635B2 (en) | 2008-08-13 | 2025-11-04 | Vertex Pharmaceuticals Incorporated | Pharmaceutical composition and administrations thereof |
| US20100074949A1 (en) | 2008-08-13 | 2010-03-25 | William Rowe | Pharmaceutical composition and administration thereof |
| EP2349223A2 (en) * | 2008-09-29 | 2011-08-03 | Vertex Pharmaceuticals Incorporated | Dosage units of 3-(6-(1-(2,2-difluorobenzo [d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid |
| AU2009308232B2 (en) | 2008-10-23 | 2016-02-04 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| CN102227424B (zh) | 2008-10-23 | 2013-08-14 | 沃泰克斯药物股份有限公司 | 囊性纤维化跨膜传导调节因子的调节剂 |
| ES2654414T3 (es) * | 2009-03-20 | 2018-02-13 | Vertex Pharmaceuticals Incorporated | Proceso de preparación de moduladores del regulador de la conductancia transmembrana de la fibrosis quística |
| HRP20181261T1 (hr) | 2009-03-20 | 2018-12-14 | Vertex Pharmaceuticals Incorporated | Modulatori regulatora transmembranske provodljivosti cistične fibroze |
| WO2011031745A1 (en) | 2009-09-09 | 2011-03-17 | Achaogen, Inc. | Antibacterial fluoroquinolone analogs |
| AU2010310612A1 (en) * | 2009-10-23 | 2012-06-14 | Vertex Pharmaceuticals Incorporated | Process for preparing modulators of cystic fibrosis transmembrane conductance regulator |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| MX2012011655A (es) | 2010-04-07 | 2012-11-23 | Vertex Pharma | Formas solidas de acido 3-(6-(1-(2,2-difluorobenzo [d][1-3]dioxol-5-il]ciclopropanocarboxamido)-3-metilpiridin-2-il) benzoico. |
| RS62767B1 (sr) | 2010-04-07 | 2022-01-31 | Vertex Pharma | Farmaceutski sastavi 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il) ciklopropankarboksamido)-3-metilpiriodin-2-il)benzojeve kiseline i njihova primena |
| EP3045452A1 (en) | 2010-04-22 | 2016-07-20 | Vertex Pharmaceuticals Inc. | Process of producing cycloalkylcarboxamido-indole compounds |
| US8563593B2 (en) | 2010-06-08 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Formulations of (R)-1-(2,2-difluorobenzo[D] [1,3] dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide |
| JP5525612B2 (ja) * | 2010-07-23 | 2014-06-18 | 国立大学法人 東京大学 | 含窒素複素環誘導体 |
| CN102816175B (zh) * | 2011-06-09 | 2015-12-16 | 上海汇伦生命科技有限公司 | 一种杂环并吡啶酮类化合物,其中间体、制备方法和用途 |
| US9254291B2 (en) | 2011-11-08 | 2016-02-09 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| CN102643268B (zh) * | 2011-12-30 | 2014-05-21 | 沈阳药科大学 | 喹啉类及噌啉类化合物及其应用 |
| LT2806859T (lt) | 2012-01-25 | 2019-10-25 | Vertex Pharma | 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioksol-5-il) ciklopropankarboksamido)-3-metilpiridin-2-il)benzenkarboksirūgšties kompozicijos |
| BR112014021090B1 (pt) | 2012-02-27 | 2023-01-24 | Vertex Pharmaceuticals Incorporated | Composição farmacêutica e uso de n-[2,4-bis(1,1-dimetiletil)-5-hidróxifenil]-1,4-di-hidro-4-oxoquinolina3-carboxamida na preparação da mesma |
| US8674108B2 (en) | 2012-04-20 | 2014-03-18 | Vertex Pharmaceuticals Incorporated | Solid forms of N-[2,4-bis(1,1-dimethylethy)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide |
| US9012496B2 (en) | 2012-07-16 | 2015-04-21 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide and administration thereof |
| CN103694163A (zh) * | 2012-09-27 | 2014-04-02 | 上海先声药物研究有限公司 | 作为钾通道调节剂的化合物 |
| CA2930199C (en) | 2013-11-12 | 2022-10-25 | Vertex Pharmaceuticals Incorporated | Process of preparing pharmaceutical compositions for the treatment of cftr mediated diseases |
| PL3925607T3 (pl) | 2014-04-15 | 2023-10-30 | Vertex Pharmaceuticals Incorporated | Kompozycje farmaceutyczne do leczenia chorób, w których pośredniczy mukowiscydozowy przezbłonowy regulator przewodnictwa |
| ES2702288T3 (es) | 2014-10-07 | 2019-02-28 | Vertex Pharma | Co-cristales de moduladores de regulador de conductancia transmembrana de la fibrosis quística |
| SI3221692T1 (sl) | 2014-11-18 | 2021-11-30 | Vertex Pharmaceuticals Inc. | Postopek za izvajanje testov visoke prepustnosti z visoko zmogljivostno tekočinsko kromatografijo |
| US10550135B2 (en) | 2016-03-30 | 2020-02-04 | Council Of Scientific & Industrial Research | Silicon incorporated quinolines with anti-malarial and anti-toxoplasmosis activity |
| DK3615527T3 (da) | 2017-06-30 | 2024-05-06 | Elanco Animal Health Gmbh | Nye azaquinolin-derivater |
| JP7402467B2 (ja) * | 2019-01-30 | 2023-12-21 | 慶應義塾 | パーキンソン病治療薬 |
| US11634349B2 (en) | 2020-03-17 | 2023-04-25 | Robert O. Hoffland | Two-stage biogas production system for anaerobic digesters |
| CR20230120A (es) | 2020-08-07 | 2023-09-01 | Vertex Pharma | Moduladores del regulador de la conductancia transmembrana de la fibrosis quística |
| US12324802B2 (en) | 2020-11-18 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| WO2024072794A1 (en) * | 2022-09-26 | 2024-04-04 | Rectify Pharmaceuticals, Inc. | Pyridine carboxamide compounds and their use in treating medical conditions |
| WO2024072793A1 (en) * | 2022-09-26 | 2024-04-04 | Rectify Pharmaceuticals, Inc. | Pyridine carboxamide compounds and their use in treating medical conditions |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0366193A3 (en) | 1988-10-24 | 1992-01-08 | Norwich Eaton Pharmaceuticals, Inc. | Novel antimicrobial quinolonyl lactams |
| US5225418A (en) * | 1991-12-17 | 1993-07-06 | Du Pont Merck Pharmaceutical Company | 5H-(1,2)benzisothiazolo[2,3-a]quinoline-5-ones and analogs as antiinflammatory agents |
| ATE198601T1 (de) | 1992-05-20 | 2001-01-15 | Merck & Co Inc | Ester derivate von 4-aza-steroiden |
| DE69329240D1 (de) | 1992-05-20 | 2000-09-21 | Merck & Co Inc | 17-ether und thioether von 4-aza-steroiden |
| ES2211965T3 (es) | 1995-08-02 | 2004-07-16 | Darwin Discovery Limited | Quinolonas y su utilizacion terapeutica. |
| DE19532235A1 (de) | 1995-08-31 | 1997-03-06 | Keppler Bernhard K Priv Doz Dr | An Phosphonsäuren gekoppelte antibakteriell wirksame Verbindungen zur Therapie von Infektionen im Bereich des Knochens |
| US7211045B2 (en) | 2002-07-22 | 2007-05-01 | Ep Medsystems, Inc. | Method and system for using ultrasound in cardiac diagnosis and therapy |
| US7138412B2 (en) | 2003-03-11 | 2006-11-21 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives useful as serine protease inhibitors |
| CA2569402A1 (en) * | 2004-06-04 | 2005-12-22 | The Regents Of The University Of California | Compounds having activity in increasing ion transport by mutant-cftr and uses thereof |
| PL2489659T3 (pl) * | 2004-06-24 | 2018-06-29 | Vertex Pharma | Modulatory transporterów posiadających kasetę wiążącą atp |
| BRPI0515319A (pt) | 2004-09-17 | 2008-07-22 | Cylene Pharmaceuticals Inc | análogos de quinolona |
| EP1807082A4 (en) | 2004-10-26 | 2010-12-01 | Janssen Pharmaceutica Nv | INHIBITOR COMPOUNDS OF XA FACTORS |
| GB0424951D0 (en) | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| GB0424959D0 (en) | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| WO2006076442A2 (en) | 2005-01-14 | 2006-07-20 | Janssen Pharmaceutica N.V. | Triazolopyrimidine derivatives |
| WO2007033232A1 (en) | 2005-09-14 | 2007-03-22 | Janssen Pharmaceutica, N.V. | 5-oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of c-fms kinase |
| TW200800983A (en) | 2005-09-14 | 2008-01-01 | Janssen Pharmaceutica Nv | 5-oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of C-FMS kinase |
| US7642270B2 (en) * | 2005-09-14 | 2010-01-05 | Janssen Pharmaceutica N.V. | 5-oxo-5,8-dihydro-pyrido-pyrimidine as inhibitors of c-fms kinase |
| JP2009521468A (ja) * | 2005-12-24 | 2009-06-04 | 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 | Ａｂｃ輸送体の調節因子としてのキノリン−４−オン誘導体 |
| AU2008256717B2 (en) * | 2007-05-25 | 2013-11-21 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| JP5389030B2 (ja) * | 2007-08-24 | 2014-01-15 | 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 | （特に）嚢胞性線維症の処置に有用なイソチアゾロピリジノン |
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| AU2008298545A1 (en) | 2009-03-19 |
| CA2699382A1 (en) | 2009-03-19 |
| US8748612B2 (en) | 2014-06-10 |
| US20130018070A1 (en) | 2013-01-17 |
| AU2008298545B2 (en) | 2013-12-12 |
| US20100261750A1 (en) | 2010-10-14 |
| US8410132B2 (en) | 2013-04-02 |
| WO2009036412A1 (en) | 2009-03-19 |
| EP2201010B1 (en) | 2013-11-06 |
| CN101821266B (zh) | 2014-03-12 |
| NZ583878A (en) | 2012-10-26 |
| JP2010539185A (ja) | 2010-12-16 |
| JP5461405B2 (ja) | 2014-04-02 |
| US8188283B2 (en) | 2012-05-29 |
| CN101821266A (zh) | 2010-09-01 |
| ES2445442T3 (es) | 2014-03-03 |
| US20130178496A1 (en) | 2013-07-11 |
| EP2201010A1 (en) | 2010-06-30 |
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