HRP20140695T1 - Modulatori cistiäśno-fibroznog transmembranskog regulatora provodljivosti - Google Patents

Modulatori cistiäśno-fibroznog transmembranskog regulatora provodljivosti Download PDF

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HRP20140695T1
HRP20140695T1 HRP20140695AT HRP20140695T HRP20140695T1 HR P20140695 T1 HRP20140695 T1 HR P20140695T1 HR P20140695A T HRP20140695A T HR P20140695AT HR P20140695 T HRP20140695 T HR P20140695T HR P20140695 T1 HRP20140695 T1 HR P20140695T1
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Croatia
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disease
compound
image
formula
syndrome
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HRP20140695AT
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Hayley Binch
Lev T. D. Fanning
Dennis Hurley
Urvi Sheth
Alina Silina
Xiaoqing Yang
Martyn Botfield
Peter D. J. Grootenhuis
Fredrick Van Goor
Mehdi Michel Djamel Numa
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Vertex Pharmaceuticals Incorporated
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Application filed by Vertex Pharmaceuticals Incorporated filed Critical Vertex Pharmaceuticals Incorporated
Publication of HRP20140695T1 publication Critical patent/HRP20140695T1/hr

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Claims (45)

1. Spoj sa formulom (I): [image] ili njegove farmaceutski prihvatljive soli, naznačen time da: prsten A je odabran od: [image] pri čemu: R1 je -CF3, -CN, ili -C≡CCH2N(CH3)2; R2 je vodik, -CH3, -CF3, -OH, ili -CH2OH; R3 je vodik, -CH3, -OCH3, ili -CN; pod uvjetom da oba R2 i R3 nisu istovremeno vodik.
2. Spoj prema zahtjevu 1, naznačen time da prsten A je [image]
3. Spoj prema zahtjevu 1, naznačen time da prsten A je [image]
4. Spoj prema zahtjevu 1, naznačen time da prsten A je [image]
5. Spoj prema zahtjevu 1, naznačen time da prsten A je [image]
6. Spoj prema bilo kojem zahtjevu od 2-5, naznačen time da R1 je -CF3.
7. Spoj prema bilo kojem zahtjevu od 2-5, naznačen time da R1 je -CN.
8. Spoj prema bilo kojem zahtjevu od 2-5, naznačen time da R1 je -C≡CCH2N(CH3)2.
9. Spoj prema bilo kojem zahtjevu od 6-8, naznačen time da R2 je vodik.
10. Spoj prema bilo kojem zahtjevu od 6-8, naznačen time da R2 je -CH3.
11. Spoj prema bilo kojem zahtjevu od 6-8, naznačen time da R2 je -CF3.
12. Spoj prema bilo kojem zahtjevu od 6-8, naznačen time da R2 je -OH.
13. Spoj prema bilo kojem zahtjevu od 6-8, naznačen time da R2 je -CH2OH.
14. Spoj prema bilo kojem zahtjevu od 10-13, naznačen time da R3 je vodik.
15. Spoj prema bilo kojem zahtjevu od 9-13, naznačen time da R3 je -CH3.
16. Spoj prema bilo kojem zahtjevu od 9-13, naznačen time da R3 je -OCH3.
17. Spoj prema bilo kojem zahtjevu od 9-13, naznačen time da R3 je -CN.
18. Spoj prema zahtjevu 1, naznačen time da je spoj odabran od: [image] [image] [image] [image] [image]
19. Spoj prema zahtjevu 18, naznačen time da je spoj: [image]
20. Farmaceutski pripravak naznačen time da sadrži spoj prema bilo kojem zahtjevu od 1-19 i farmaceutski prihvatljiv nosač ili adjuvant.
21. Farmaceutski pripravak prema zahtjevu 20, naznačen time da dodatno sadrži dodatno sredstvo koje je odabrano od mukolitičkog sredstva, bronhodilatora, antibiotika, anti-infektivnog sredstva, protuupalnog sredstva, CFTR modulatora koji je različit od spoja sa formulom (I), ili prehrambenog sredstva.
22. Farmaceutski pripravak prema zahtjevu 21, naznačen time da je navedeno dodatno sredstvo CFTR modulator koji je različit od spoja sa formulom (I).
23. Spoj prema bilo kojem zahtjevu od 1-19 naznačen time da je za uporabu kod liječenja ili smanjivanja težine bolesti kod pacijenta, naznačen time da navedena bolest je odabrana od cistične fibroze, astme, dimom uzrokovane KOPB, kroničnog bronhitisa, rinosinusitisa, konstipacije, pankreatitisa, insuficijencije pankreasa, muške neplodnosti uzrokovane urođenom obostranom agenezijom duktus deferensa (CBAVD), blage bolesti pluća, idiopatskog pankreatitisa, alergijske bronhopulmonalne aspergiloze (ABPA), bolesti jetre, nasljednog emfizema, nasljedne hemokromatoze, nedostataka koagulacije-fibrinolize, kao nedostatka proteina C, nasljednog angioedema Tip 1, nedostataka obrade lipida, kao što su obiteljska hiperkolesterolemija, kilomikronemija Tip 1, abetalipoproteinemija, lizosomskih bolesti nakupljanja, kao što su bolest I-stanica /pseudo-Hurler, mukopolisaharidoze, Sandhof/Tay-Sachs, sindrom Crigler-Najjar tip II, poliendokrinopatija/hiperinzulinemija, dijabetes melitus, Laronov sindrom patuljastog rasta, nedostatak mijeloperoksidaze, primarni hipoparatiroidizam, melanoma, glikogenoze CDG tip 1, urođenog hipertireoidizma, osteogeneza imperfekta, nasljedne hipofibrinogenemija, nedostatka ACT, insipidni dijabetes (DI), neurohipofizealni DI, nefrogeni DI, Charcot-Marie Tooth sindrom, Pelizaeus-Merzbacherova bolest, neurodegenerativne bolesti kao što su Alzheimerova bolest, Parkinsonova bolest, amiotrofična lateralna skleroza, progresivna supranuklearna paraliza, Pick-ova bolest, ozbiljni neuroloških poremećaji poliglutamina kao što su Huntingtonov, spinocerebelarna ataksija tip I, spinalna i bulbarna mišićna atrofija, dentato-rubro-palido-Luysiana atrofija, i miotonična distrofija, kao i spongiformne encefalopatije, kao što su nasljedna Creutzfeldt-Jakobova bolest (zbog nedostatka obrade prionskih proteina), Fabrijeva bolest, sindrom Gerstmann-Sträussler-Scheinker, KOPB, bolest suhog oka, insuficijencija pankreasa, osteoporoza, osteopenija, Gorhamov sindrom, kloridne kanalopatije, kongenitalna miotonija (Thomsonovi i Beckerovi oblici), Bartter-ov sindrom tip III, Dent-ova bolest, hiperekpleksija, epilepsija, lizosomske bolesti nakupljanja, Angelman-ovog sindroma, primarne cilijarne diskinezije (PCD), PCD sa situs inversus (također poznata kao Kartagenerov sindrom), PCD bez situs inversus i cilijarne aplazije, ili Sjogrenova bolest.
24. Spoj za uporabu prema zahtjevu 23, naznačen time da je navedena bolest cistična fibroza.
25. Spoj za uporabu prema zahtjevu 23, naznačen time da je navedena bolest povezana sa smanjenom funkcijom CFTR zbog mutacija u genu koji kodira CFTR ili zbog faktora okoline, pri čemu je bolest cistična fibroza, kronični bronhitis, rekurentni bronhitis, akutni bronhitis, muška neplodnost uzrokovana sa urođenom obostranom agenezijom duktus deferensa (CBAVD), ženska neplodnost uzrokovana sa urođenim nedostatkom uterusa i vagine (CAUV), idiopatski kronični pankreatitis (ICP), idiopatski rekurentni pankreatitis, idiopatski akutni pankreatitis, kronični rinosinusitis, primarni sklerozni kolangitis, alergijska bronhopulmonarna aspergiloza, dijabetes, sindrom suhog oka, konstipacija, alergijska bronhopulmonalna aspergiloza (ABPA), bolesti kostiju, ili astma.
26. Spoj za uporabu prema zahtjevu 23, naznačen time da je navedena bolest povezana s normalnom funkcijom CFTR.
27. Spoj za uporabu prema zahtjevu 26, naznačen time da je bolest kronična opstruktivna plućna bolest (KOPB), kronični bronhitis, rekurentni bronhitis, akutni bronhitis, rinosinusitis, konstipacija, kronični pankreatitis, rekurentni pankreatitis, te akutni pankreatitis, insuficijencija pankreasa, muška neplodnost uzrokovana sa urođenom obostranom agenezijom duktus deferensa (CBAVD), blaga bolest pluća, idiopatski pankreatitis, bolest jetre, nasljedni emfizem, žučni kamenci, gastro-ezofagealna refluksna bolest, gastrointestinalne maligne bolesti, upalna bolest crijeva, konstipacija, dijabetes, artritis, osteoporoza, ili osteopenija.
28. Spoj za uporabu prema zahtjevu 26, naznačen time da je bolest nasljedna hemokromatoza, nedostatci koagulacije-fibrinolize, kao nedostatak proteina C, nasljedni angioedema Tip 1, nedostatak obrade lipida, kao što je obiteljska hiperkolesterolemija, kilomikronemija Tip 1, abetalipoproteinemija, lizosomske bolesti nakupljanja, kao što je bolest I-stanica/pseudo-Hurler, mukopolisaharidoze, sindrom Sandhof/Tay-Sachs, sindrom Crigler-Najjar tip II, poliendokrinopatija/hiperinzulinemija, dijabetes melitus, Laronov sindrom patuljastog rasta, nedostatak mijeloperoksidaze, primarni hipoparatiroidizam, melanom, glikogenoza CDG tip 1, urođeni hipertireoidizam, osteogeneza imperfekta, nasljedna hipofibrinogenemija, nedostatak ACT, insipidni dijabetes (DI), neurohipofizealni DI, nefrogeni DI, Charcot-Marie Tooth sindrom, Pelizaeus-Merzbacherova bolest, neurodegenerativne bolesti kao što su Alzheimerova bolest, Parkinsonova bolest, amiotrofična lateralna skleroza, progresivna supranuklearna paraliza, Pick-ova bolest, ozbiljni neuroloških poremećaji poliglutamina kao što su Huntingtonov, spinocerebelarna ataksija tip I, spinalna i bulbarna mišićna atrofija, dentato-rubro-palido-Luysiana atrofija, te miotonična distrofija, kao i spongiformne encefalopatije, kao što su nasljedna Creutzfeldt-Jakobova bolest (zbog nedostatka obrade prionskih proteina), Fabrijeva bolest, sindrom Gerstmann-Sträussler-Scheinker, KOPB, bolest suhog oka, insuficijencija pankreasa, osteoporoza, osteopenija, Gorham-ov sindrom, kloridne kanalopatije, kongenitalna miotonija (Thomsonovi i Beckerovi oblici), Bartter-ov sindrom tip III, Dent-ova bolest, hiperekpleksija, epilepsija, lizosomske bolesti nakupljanja, Angelman-ov sindroma, primarna cilijarna diskinezija (PCD), PCD sa situs inversus (također poznata kao Kartagenerov sindrom), PCD bez situs inversus i cilijarne aplazije, ili Sjogrenova bolest.
29. Komplet za uporabu za mjerenje aktivnosti CFTR ili njegovog fragmenta u in vitro ili in vivo biološkom uzorku, naznačen time da sadrži: (i) pripravak koji sadrži spoj sa formulom (I) prema bilo kojem zahtjevu od 1-19; (ii) instrukcije za: a) kontakt pripravka s biološkim uzorkom; b) mjerenje aktivnosti navedenog CFTR ili njegovog fragmenta.
30. Komplet prema zahtjevu 29, naznačen time da dodatno sadrži instrukcije za: a) kontakt dodatnog spoja s biološkim uzorkom; b) mjerenje aktivnosti navedenog CFTR ili njegovog fragmenta u prisutnosti navedenog dodatnog spoja, te c) usporedbu aktivnosti CFTR ili njegovog fragmenta u prisutnosti dodatnog spoja sa aktivnošću CFTR ili njegovog fragmenta u prisutnosti pripravka prema Formuli (I) prema bilo kojem zahtjevu od 1-18.
31. Komplet prema zahtjevu 30, naznačen time da korak usporedbe aktivnosti navedenog CFTR ili njegovog fragmenta daje mjeru gustoće CFTR ili njegovog fragmenta.
32. In-vitro postupak za modulaciju CFTR aktivnosti u biološkom uzorku naznačen time da sadrži korak kontakta navedenog CFTR sa spojem prema bilo kojem zahtjevu od 1-19.
33. Postupak za pripravu spoja sa formulom (Ic), [image] ili njegove farmaceutski prihvatljive soli, naznačen time da sadrži korake: (a) reakciju spoja sa formulom 2a sa aminom sa formulom 3 da se dobije spoj sa formulom 2b [image] (b) konverziju spoja sa formulom 2b u amin sa formulom 2c putem redukcije [image] te (c) reakciju amina sa formulom 2c sa kiselinom sa formulom 1d da se dobije spoj sa Formulom (Ic) [image] pri čemu Hal je F, Cl, Br, ili I; amin sa formulom 3 je [image] i prsten A je odabran od: [image] pri čemu R1 je -CF3, -CN, ili -C≡CCH2N(CH3)2; R2 je vodik, -CH3, -CF3, -OH, ili -CH2OH; R3 je vodik, -CH3, -OCH3, ili -CN; pod uvjetom da oba R2 i R3 nisu istovremeno vodik, i Ra je vodik ili silil zaštitna skupina odabrana iz skupine koja sadrži trimetilsilil (TMS), tert-butildifenilsilil (TBDPS), tert-butildimetilsilil (TBDMS), triizopropilsilil (TIPS), te [2-(trimetilsilil)etoksi]metil (SEM).
34. Postupak prema zahtjevu 33, naznačen time da se amin sa formulom 3 u koraku (a) dobiva in situ od hidrokloridne soli amina.
35. Postupak prema zahtjevu 34, naznačen time da Ra je TBDMS.
36. Postupak prema zahtjevu 35, naznačen time da se korak (a) provodi u acetonitrilu u prisutnosti trietilamina.
37. Postupak prema zahtjevu 33, naznačen time da se korak (b) provodi u prisutnosti paladijevog katalizatora, pri čemu otapalo sadrži metanol ili etanol.
38. Postupak prema zahtjevu 33, naznačen time da se korak (b) provodi u vodi u prisutnosti Fe i FeSO4 ili Zn i AcOH.
39. Postupak prema zahtjevu 33, naznačen time da se korak (c) provodi u otapalu u prisutnosti O-(7-azabenzotriazol-1-il)-N,N,N',N'-tetrametiluronij heksafluorofosfata (HATU) i trietilamina ili u otapalu u prisutnosti propil fosfonskog kiselog cikličkog anhidrida (T3P®) i pridina.
40. Postupak prema zahtjevu 39, naznačen time da otapalo u koraku (c) sadrži N,N-dimetil formamid (DMF), etil acetat, ili 2-metiltetrahidrofuran.
41. Postupak prema zahtjevu 40, naznačen time da Ra je TBDMS.
42. Postupak prema zahtjevu 33 naznačen time da dodatno sadrži reakciju deprotekcije kada prsten A je [image] naznačen time da Ra je silil zaštitna skupina, da de dobije spoj sa formulom (I), pri čemu prsten A je; [image]
43. Spoj koji je [image] naznačen time da prsten A je [image] pri čemu R1 je -CF3, -CN, ili -C≡CCH2N(CH3)2, i Ra je vodik ili silil zaštitna skupina odabrana iz skupine koja sadrži trimetilsilil (TMS), tert-butildifenilsilil (TBDPS), tert-butildimetilsilil (TBDMS), triizopropilsilil (TIPS), te [2-(trimetilsilil)etoksi]metil (SEM).
44. Spoj koji je [image] naznačen time da prsten A je [image] pri čemu R1 je -CF3, -CN, ili -C≡CCH2N(CH3)2, i Ra je vodik ili silil zaštitna skupina odabrana iz skupine koja sadrži trimetilsilil (TMS), tert-butildifenilsilil (TBDPS), tert-butildimetilsilil (TBDMS) triizopropilsilil (TIPS), te [2-(trimetilsilil)etoksi]metil (SEM).
45. Spoj sa formulom (IA): [image] ili njegove farmaceutski prihvatljive soli, naznačen time da: prsten A je odabran od [image] pri čemu R1 je -CF3, -CN, ili -C≡CCH2N(CH3)2; R2 je vodik, -CH3, -CF3, -OH, ili -CH2OH; R3 je vodik, -CH3, -OCH3, ili -CN; pod uvjetom da oba R2 i R3 nisu istovremeno vodik, i Ra je silil zaštitna skupina odabrana iz skupine koja sadrži trimetilsilil (TMS), tert-butildifenilsilil (TBDPS), tert-butildimetilsilil (TBDMS), triizopropilsilil (TIPS), te [2-(trimetilsilil)etoksi]metil (SEM).
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Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
KR20060088537A (ko) 2003-09-06 2006-08-04 버텍스 파마슈티칼스 인코포레이티드 Ａｔｐ-결합 카세트 수송체의 조절자
ZA200604578B (en) * 2003-11-14 2008-05-28 Vertex Pharma 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
AU2005244153B2 (en) 2004-05-17 2009-10-29 Corus Pharma, Inc. Aerosolized fosfomycin/aminoglycoside combination for the treatment of bacterial respiratory infections
NZ587551A (en) * 2004-06-24 2012-01-12 Vertex Pharma 5-Amino-phenol derivatives such as 5-amino-2,4-di-tert-butyl-phenol
EP1912983B1 (en) * 2005-08-11 2011-06-08 Vertex Pharmaceuticals, Inc. Modulators of cystic fibrosis transmembrane conductance regulator
EP3696174A1 (en) * 2005-11-08 2020-08-19 Vertex Pharmaceuticals Incorporated Heterocyclic modulators of atp-binding cassette transporters
PL3219705T3 (pl) 2005-12-28 2020-08-10 Vertex Pharmaceuticals Incorporated Kompozycje farmaceutyczne amorficznych postaci n-[2,4-bis(1,1-dimetyloetylo)-5-hydroksyfenylo]-1,4-dihydro-4-oksochinolino-3-karboksyamidu
US7671221B2 (en) * 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
US7691902B2 (en) 2005-12-28 2010-04-06 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
SI2674428T1 (sl) * 2006-04-07 2016-07-29 Vertex Pharmaceuticals Incorporated Modulatorji transporterjev atp-vezavne kasete
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
US8563573B2 (en) * 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
CN101687842B (zh) 2007-05-09 2013-03-06 沃泰克斯药物股份有限公司 Cftr调节剂
EP2187884B1 (en) 2007-08-24 2016-03-30 Vertex Pharmaceuticals Incorporated Isothiazolopyridinones useful for the treatment of (inter alia) cystic fibrosis
DK2217572T3 (da) 2007-11-16 2014-02-03 Vertex Pharma Isoquinoliner som modulatorer af ATP-bindingskassettetransportører
US20100036130A1 (en) * 2007-12-07 2010-02-11 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
LT2639223T (lt) 2007-12-07 2017-06-26 Vertex Pharmaceuticals Incorporated Cikloalkilkarboksiamido-piridino benzenkarboksirūgščių gamybos būdas
CN103626744B (zh) 2007-12-07 2016-05-11 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)苯甲酸的固体形式
EA201070699A1 (ru) * 2007-12-07 2011-02-28 Вертекс Фармасьютикалз Инкорпорейтед Композиции 3-(6-(1-2,2-дифторбензо[d][1,3]диоксол-5-ил)циклопропанкарбоксамидо)-3-метилпиридин-2-ил)бензойной кислоты
ES2647531T3 (es) 2008-02-28 2017-12-22 Vertex Pharmaceuticals Incorporated Derivados de heteroarilo como moduladores de CFTR
ES2552990T3 (es) 2008-03-31 2015-12-03 Vertex Pharmaceuticals Incorporated Derivados de piridilo como moduladores del CFTR
WO2010037066A2 (en) 2008-09-29 2010-04-01 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
AU2009308284B2 (en) * 2008-10-23 2016-02-04 Vertex Pharmaceuticals, Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US20110257223A1 (en) * 2008-10-23 2011-10-20 Vertex Pharmaceuticals Incorporated Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
KR101852173B1 (ko) 2009-03-20 2018-04-27 버텍스 파마슈티칼스 인코포레이티드 낭성 섬유증 막횡단 전도도 조절자의 조정자의 제조 방법
CN102498112B (zh) 2009-09-17 2015-05-20 沃泰克斯药物股份有限公司 制备氮杂二环化合物的方法
MX2012004791A (es) * 2009-10-23 2013-02-01 Vertex Pharma Formas sólidas de n-(4-(7-azabiciclo[2.2.1]heptan-7-il)-2-(trifluo rometil)fenil)-4-oxo-5-(trifluorometil)-1,4-dihidroquinolina-3-ca rboxamida.
US8344147B2 (en) * 2009-10-23 2013-01-01 Vertex Pharmaceutical 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
WO2011127241A2 (en) 2010-04-07 2011-10-13 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyriodin-2-yl)benzoic acid and administration thereof
RS54783B1 (sr) 2010-04-07 2016-10-31 Vertex Pharma Čvrste forme 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il)ciklopropankarboksiamido)-3-metilpiridin-2-il)benzoeve kiseline
AU2011242454A1 (en) 2010-04-22 2012-11-08 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
CN103038214B (zh) 2010-04-22 2015-09-30 弗特克斯药品有限公司 制备环烷基甲酰胺基-吲哚化合物的方法
NZ603044A (en) * 2010-04-22 2015-08-28 Vertex Pharma Pharmaceutical compositions comprising cftr modulators and administrations thereof
WO2011137427A2 (en) * 2010-04-30 2011-11-03 The Johns Hopkins University Compositions and methods for treating pulmonary conditions
AR081920A1 (es) * 2010-05-20 2012-10-31 Vertex Pharma Procesos de produccion de moduladores del regulador de conductancia transmembrana de fibrosis quistica
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
HUE025653T2 (hu) 2010-10-08 2016-04-28 Nivalis Therapeutics Inc Új, szubsztituált kinolin-vegyületek S-nitrozoglutation-reduktáz inhibitorokként
CN103328430A (zh) 2010-12-16 2013-09-25 N30医药品公司 作为s-亚硝基谷胱甘肽还原酶抑制剂的新型取代的双环芳族化合物
AU2012222869B2 (en) * 2011-03-02 2015-08-13 Bionomics Limited Methods of treating a disease or condition of the central nervous system
HUE047354T2 (hu) 2011-05-18 2020-04-28 Vertex Pharmaceuticals Europe Ltd Ivacaftor deuterizált származékai
WO2012170371A1 (en) * 2011-06-10 2012-12-13 N30 Pharmaceuticals, Llc Compounds as s-nitrosoglutathione reductase inhibitors
ME02650B (me) 2011-11-08 2017-06-20 Vertex Pharma Modulatori atp- vezujućih kasetnih transportera
CN109966264A (zh) 2012-02-27 2019-07-05 沃泰克斯药物股份有限公司 药物组合物及其施用
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
CA2878057A1 (en) 2012-07-16 2014-01-23 Rossitza Gueorguieva Alargova 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
KR102280372B1 (ko) 2013-11-12 2021-07-22 버텍스 파마슈티칼스 인코포레이티드 Cftr 매개된 질환 치료용 약제학적 조성물의 제조 방법
PL3925607T3 (pl) 2014-04-15 2023-10-30 Vertex Pharmaceuticals Incorporated Kompozycje farmaceutyczne do leczenia chorób, w których pośredniczy mukowiscydozowy przezbłonowy regulator przewodnictwa
GB201415381D0 (en) 2014-08-29 2014-10-15 Algipharma As Inhalable powder formulations of alginate oligomers
TWI735416B (zh) 2014-10-06 2021-08-11 美商維泰克斯製藥公司 囊腫纖維化症跨膜傳導調節蛋白之調節劑
US9701639B2 (en) 2014-10-07 2017-07-11 Vertex Pharmaceuticals Incorporated Co-crystals of modulators of cystic fibrosis transmembrane conductance regulator
CN107110831B (zh) 2014-11-18 2020-02-21 弗特克斯药品有限公司 进行高通量试验高效液相色谱的方法
GB201504878D0 (en) 2015-03-23 2015-05-06 Algipharma As Use of alginate oligomers and CFTR modulators in the treatment of conditions associated with CFTR dysfuntion
US10399946B2 (en) 2015-09-10 2019-09-03 Laurel Therapeutics Ltd. Solid forms of an S-Nitrosoglutathione reductase inhibitor
CA2999529A1 (en) 2015-09-25 2017-03-30 Vertex Pharmaceuticals (Europe) Limited Deuterated cftr potentiators
GB201517639D0 (en) 2015-10-06 2015-11-18 Algipharma As Use of alginate oligomers to treat or prevent microbial overgrowth in the intestinal tract
US10138227B2 (en) * 2016-06-03 2018-11-27 Abbvie S.Á.R.L. Heteroaryl substituted pyridines and methods of use
WO2018107100A1 (en) 2016-12-09 2018-06-14 Vertex Pharmaceuticals Incorporated Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
CA3066084A1 (en) 2017-06-08 2018-12-13 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
MA49631A (fr) 2017-07-17 2020-05-27 Vertex Pharma Méthodes de traitement de la fibrose kystique
WO2019109021A1 (en) 2017-12-01 2019-06-06 Vertex Pharmaceuticals Incorporated Processes for making modulators of cystic fibrosis transmembrane conductance regulator
WO2019113476A2 (en) 2017-12-08 2019-06-13 Vertex Pharmaceuticals Incorporated Processes for making modulators of cystic fibrosis transmembrane conductance regulator
US11066417B2 (en) * 2018-02-15 2021-07-20 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulators
CA3150162A1 (en) 2019-08-14 2021-02-18 Vertex Pharmaceuticals Incorporated Crystalline forms of cftr modulators
TW202115092A (zh) 2019-08-14 2021-04-16 美商維泰克斯製藥公司 囊腫纖維化跨膜傳導調節蛋白之調節劑
WO2021113808A1 (en) * 2019-12-05 2021-06-10 Genzyme Corporation Cftr-modulating arylamides
JP2023529311A (ja) * 2020-05-27 2023-07-10 アリエル プレシジョン メディスン、インク． Ｃｆｔｒ関連疾患および障害を治療する方法

Family Cites Families (104)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IE52670B1 (en) 1981-03-03 1988-01-20 Leo Ab Heterocyclic carboxamides,compositions containing such compounds,and processes for their preparation
FR2509728A1 (fr) 1981-07-17 1983-01-21 Roussel Uclaf Nouveaux derives de la quinoleine, leurs sels, procede de preparation, application a titre de medicaments et compositions les renfermant
FR2537140B1 (fr) 1982-12-07 1986-07-18 Roussel Uclaf Nouveaux derives de la 4-hydroxy-3-quinoleine carboxamide, leur sels, procede de preparation, application a titre de medicaments, et compositions les renfermant
DE3702393A1 (de) 1987-01-28 1988-08-11 Bayer Ag 8-cyano-1-cyclopropyl-1,4-dihydro-4-oxo- 3-chinolincarbonsaeuren, verfahren zu ihrer herstellung und diese enthaltende antibakterielle mittel
DE3811341A1 (de) 1987-10-09 1989-04-27 Bayer Ag In 7-stellung c-verknuepfte chinolon- und 1,8-naphthyridin-4-on-carbonsaeure und ein verfahren zu ihrer herstellung
EP0324521A3 (en) 1988-01-11 1991-11-27 Duphar International Research B.V Method of treating haematologic diseases and pharmaceutical compositions to be used therefor
US5304121A (en) 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
US5994341A (en) 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
US6099562A (en) 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
DE69628019T2 (de) 1995-08-02 2004-01-22 Darwin Discovery Ltd., Slough Chinolone und deren therapeutische verwendung
US6506792B1 (en) 1997-03-04 2003-01-14 Sterix Limited Compounds that inhibit oestrone sulphatase and/or aromatase and methods for making and using
BR9711805A (pt) 1996-06-20 2002-01-15 Regents The Univesity Of Texas Compostos e métodos para providenciar preparações farmacologicamente ativas e uso dos mesmos
GB9818914D0 (en) 1998-08-28 1998-10-21 Smithkline Beecham Plc Use
AU3033500A (en) 1999-01-15 2000-08-01 Agouron Pharmaceuticals, Inc. Non-peptide glp-1 agonists
CN1361768A (zh) 1999-06-02 2002-07-31 Nps药物有限公司 代谢移变的谷氨酸盐受体拮抗剂和它们治疗中枢神经系统疾病的用途
US6348464B1 (en) 1999-11-12 2002-02-19 Guilford Pharmaceuticals, Inc. Pyrrolecarbonylimino derivatives as naaladase inhibitors
US6974806B2 (en) 2000-07-13 2005-12-13 Takeda Pharmaceutical Company Limited Lipid-rich plaque inhibitors
IL153575A0 (en) 2000-07-14 2003-07-06 Uab Research Foundation Uses for nad synthetase inhibitors
AU2001277731A1 (en) 2000-08-09 2002-02-18 Welfide Corporation Fused bicyclic amide compounds and medicinal use thereof
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
DK1379525T3 (da) 2001-02-21 2007-12-27 Astrazeneca Ab Heteropolycykliske forbindelser og anvendelse deraf som metabotropiske glutamatreceptor-antagonister
CA2448160A1 (en) 2001-05-25 2002-12-05 Queen's University At Kingston Heterocyclic beta-amino acids and their use as anti-epileptogenic agents
PL373484A1 (en) 2001-12-10 2005-09-05 Amgen Inc. Vanilloid receptor ligands and their use in treatments
CA2494048A1 (en) 2002-08-13 2004-02-19 Warner-Lambert Company Llc 4-hydroxyquinoline derivatives as matrix metalloproteinase inhibitors
US7290046B1 (en) * 2002-11-22 2007-10-30 At&T Corp. System and method for detecting customer premise equipment behind a router on a data-over-cable system
TW200503994A (en) 2003-01-24 2005-02-01 Novartis Ag Organic compounds
WO2004080972A1 (en) 2003-03-12 2004-09-23 Vertex Pharmaceuticals Incorporated Pirazole modulators of atp-binding cassette transporters
EP1646615B1 (en) 2003-06-06 2009-08-26 Vertex Pharmaceuticals Incorporated Pyrimidine derivatives as modulators of atp-binding cassette transporters
KR20060088537A (ko) 2003-09-06 2006-08-04 버텍스 파마슈티칼스 인코포레이티드 Ａｔｐ-결합 카세트 수송체의 조절자
KR20060121909A (ko) 2003-10-08 2006-11-29 버텍스 파마슈티칼스 인코포레이티드 사이클로알킬 또는 피라닐 그룹을 포함하는 ａｔｐ-결합카세트 수송자의 조절자
ZA200604578B (en) 2003-11-14 2008-05-28 Vertex Pharma 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
BRPI0507278A (pt) 2004-01-30 2007-06-26 Vertex Pharma moduladores dos transportadores do cassete de ligação ao atp
WO2005094805A1 (ja) 2004-04-01 2005-10-13 Institute Of Medicinal Molecular Design. Inc. イミン誘導体及びアミド誘導体
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
NZ587551A (en) * 2004-06-24 2012-01-12 Vertex Pharma 5-Amino-phenol derivatives such as 5-amino-2,4-di-tert-butyl-phenol
FR2873695A1 (fr) 2004-07-30 2006-02-03 Palumed Sa Molecules hybrides qa ou q est une aminoquinoleine et a est un antibiotique ou un inhibiteur de resistance), leur synthese et leurs utilisations en tant qu'agent antibacterien
US7615570B2 (en) 2004-12-13 2009-11-10 Abbott Laboratories Antagonists to the vanilloid receptor subtype 1 (VR1) and uses thereof
US20060156485A1 (en) 2005-01-14 2006-07-20 The Procter & Gamble Company Keratin dyeing compounds, keratin dyeing compositions containing them, and use thereof
EP2363128B1 (en) 2005-03-11 2016-02-17 Vertex Pharmaceuticals Incorporated Indole modulators of ATP-binding cassette transporters
EP1891018B1 (en) 2005-05-24 2011-11-16 Vertex Pharmaceuticals, Inc. Modulators of atp-binding cassette transporters
EP1912983B1 (en) 2005-08-11 2011-06-08 Vertex Pharmaceuticals, Inc. Modulators of cystic fibrosis transmembrane conductance regulator
US8338607B2 (en) 2005-10-06 2012-12-25 Nippon Soda Co., Ltd. Cyclic amine compounds and agents for pest control
US8314256B2 (en) 2005-10-06 2012-11-20 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
US20120232059A1 (en) 2005-11-08 2012-09-13 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette Transporters
EP3696174A1 (en) 2005-11-08 2020-08-19 Vertex Pharmaceuticals Incorporated Heterocyclic modulators of atp-binding cassette transporters
WO2007071055A1 (en) 2005-12-21 2007-06-28 Painceptor Pharma Corporation Compositions and methods for modulating gated ion channels
US20090105272A1 (en) 2005-12-24 2009-04-23 Grootenhuis Peter D J Prodrugs of modulators of ABC transporters
AU2006331565A1 (en) 2005-12-27 2007-07-05 Vertex Pharmaceuticals Incorporated Compounds useful in CFTR assays and methods therewith
PL3219705T3 (pl) 2005-12-28 2020-08-10 Vertex Pharmaceuticals Incorporated Kompozycje farmaceutyczne amorficznych postaci n-[2,4-bis(1,1-dimetyloetylo)-5-hydroksyfenylo]-1,4-dihydro-4-oksochinolino-3-karboksyamidu
US7671221B2 (en) 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
US7691902B2 (en) 2005-12-28 2010-04-06 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
PE20071025A1 (es) 2006-01-31 2007-10-17 Mitsubishi Tanabe Pharma Corp Compuesto amina trisustituido
SI2674428T1 (sl) 2006-04-07 2016-07-29 Vertex Pharmaceuticals Incorporated Modulatorji transporterjev atp-vezavne kasete
US7645789B2 (en) 2006-04-07 2010-01-12 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
US7553855B2 (en) 2006-05-12 2009-06-30 Vertex Pharmaceuticals Incorporated Compositions of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
WO2008031556A2 (en) 2006-09-12 2008-03-20 Ucb Pharma, S.A. 2 amino-pyrimidine derivatives as h4 receptor antagonists, processes for preparing them and their use in pharmaceutical compositions
US8563573B2 (en) 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
US7754739B2 (en) 2007-05-09 2010-07-13 Vertex Pharmaceuticals Incorporated Modulators of CFTR
EP2073799A4 (en) 2007-03-12 2009-08-19 Vm Discovery Inc NOVEL ACTIVE SUBSTANCES FROM CALCIUMIONAL CHANNEL MODULATORS
US8039505B2 (en) 2007-04-11 2011-10-18 University Of Utah Research Foundation Compounds for modulating T-cells
WO2008147952A1 (en) 2007-05-25 2008-12-04 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US7928111B2 (en) 2007-06-08 2011-04-19 Senomyx, Inc. Compounds including substituted thienopyrimidinone derivatives as ligands for modulating chemosensory receptors
GB0713686D0 (en) 2007-07-13 2007-08-22 Addex Pharmaceuticals Sa New compounds 2
JP4846769B2 (ja) 2007-07-30 2011-12-28 田辺三菱製薬株式会社 医薬組成物
JP4834699B2 (ja) 2007-07-30 2011-12-14 田辺三菱製薬株式会社 医薬組成物
WO2009023509A2 (en) 2007-08-09 2009-02-19 Vertex Pharmaceuticals Incorporated Therapeutic combinations useful in treating cftr related diseases
EP2187884B1 (en) 2007-08-24 2016-03-30 Vertex Pharmaceuticals Incorporated Isothiazolopyridinones useful for the treatment of (inter alia) cystic fibrosis
NZ583878A (en) 2007-09-14 2012-10-26 Vertex Pharma Modulators of ABC transporter and cystic fibrosis transmembrane conductance regulator (CFTR)
US8163772B2 (en) 2007-09-14 2012-04-24 Vertex Pharmaceuticals Incorporated Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxypheny1]-1,4-dihydro-4-oxoquinoline-3-carboxamide
DK2217572T3 (da) 2007-11-16 2014-02-03 Vertex Pharma Isoquinoliner som modulatorer af ATP-bindingskassettetransportører
LT2639223T (lt) 2007-12-07 2017-06-26 Vertex Pharmaceuticals Incorporated Cikloalkilkarboksiamido-piridino benzenkarboksirūgščių gamybos būdas
EA201070699A1 (ru) 2007-12-07 2011-02-28 Вертекс Фармасьютикалз Инкорпорейтед Композиции 3-(6-(1-2,2-дифторбензо[d][1,3]диоксол-5-ил)циклопропанкарбоксамидо)-3-метилпиридин-2-ил)бензойной кислоты
US20100036130A1 (en) 2007-12-07 2010-02-11 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
CN103626744B (zh) 2007-12-07 2016-05-11 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)苯甲酸的固体形式
MY152955A (en) 2007-12-10 2014-12-15 Novartis Ag Pyrazine-2-carboxamide derivatives to treat diseases mediated by blockade of the epithelial sodium channel
EP2231671B1 (en) 2007-12-13 2013-04-24 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
ES2647531T3 (es) 2008-02-28 2017-12-22 Vertex Pharmaceuticals Incorporated Derivados de heteroarilo como moduladores de CFTR
ES2552990T3 (es) 2008-03-31 2015-12-03 Vertex Pharmaceuticals Incorporated Derivados de piridilo como moduladores del CFTR
EP3345625B1 (en) 2008-08-13 2020-12-09 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
US20100256184A1 (en) 2008-08-13 2010-10-07 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
WO2010037066A2 (en) 2008-09-29 2010-04-01 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
EP2358680B1 (en) 2008-10-23 2013-03-20 Vertex Pharmaceuticals Incorporated Solid forms of n-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide
JP5645834B2 (ja) 2008-10-23 2014-12-24 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Ｖｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ 嚢胞性線維症膜コンダクタンス制御因子の修飾因子
AU2009308284B2 (en) 2008-10-23 2016-02-04 Vertex Pharmaceuticals, Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US20110257223A1 (en) * 2008-10-23 2011-10-20 Vertex Pharmaceuticals Incorporated Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
WO2010073078A2 (en) 2008-12-22 2010-07-01 Orchid Research Laboratories Ltd. Heterocyclic compounds as hdac inhibitors
EP2382197B1 (en) 2008-12-30 2016-10-05 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
HUE038854T2 (hu) 2009-03-20 2018-12-28 Vertex Pharma Cisztás fibrózis transzmembrán konduktancia regulátor modulátorai
KR101852173B1 (ko) 2009-03-20 2018-04-27 버텍스 파마슈티칼스 인코포레이티드 낭성 섬유증 막횡단 전도도 조절자의 조정자의 제조 방법
US8809382B2 (en) 2009-05-04 2014-08-19 The Royal Institution For The Advancement Of Learning/Mcgill University 5-oxo-ETE receptor antagonist compounds
JP2011042643A (ja) 2009-07-24 2011-03-03 Bayer Cropscience Ag 殺虫性カルボキサミド類
JP2011057661A (ja) 2009-08-14 2011-03-24 Bayer Cropscience Ag 殺虫性カルボキサミド類
CN102498112B (zh) 2009-09-17 2015-05-20 沃泰克斯药物股份有限公司 制备氮杂二环化合物的方法
AU2010310449A1 (en) 2009-10-22 2012-05-03 Vertex Pharmaceuticals Incorporated Compositions for treatment of cystic fibrosis and other chronic diseases
MX2012004791A (es) * 2009-10-23 2013-02-01 Vertex Pharma Formas sólidas de n-(4-(7-azabiciclo[2.2.1]heptan-7-il)-2-(trifluo rometil)fenil)-4-oxo-5-(trifluorometil)-1,4-dihidroquinolina-3-ca rboxamida.
US8344147B2 (en) 2009-10-23 2013-01-01 Vertex Pharmaceutical Incorporated Process for preparing modulators of cystic fibrosis transmembrane conductance regulator
RS54783B1 (sr) 2010-04-07 2016-10-31 Vertex Pharma Čvrste forme 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il)ciklopropankarboksiamido)-3-metilpiridin-2-il)benzoeve kiseline
AR081920A1 (es) 2010-05-20 2012-10-31 Vertex Pharma Procesos de produccion de moduladores del regulador de conductancia transmembrana de fibrosis quistica
US20110288122A1 (en) 2010-05-20 2011-11-24 Vertex Pharmaceuticals Incorporated Pharmaceutical Compositions and Administrations Thereof
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
AU2011293658B2 (en) 2010-08-23 2015-03-05 Vertex Pharmaceuticals Incorporated Pharmaceutical composition of (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxy propyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl) cyclopropanecarboxamide and administration thereof
WO2012027731A2 (en) 2010-08-27 2012-03-01 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
US8802700B2 (en) 2010-12-10 2014-08-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters

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