发明名称 Modulators of ATP-binding cassette transporters
摘要 Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
申请公布号 US8912199(B2) 申请公布日期 2014.12.16
申请号 US201314058839 申请日期 2013.10.21
申请人 Vertex Pharmaceuticals Incorporated 发明人 Hadida Ruah Sara S.;Grootenhuis Peter D. J.;Van Goor Fredrick;Zhou Jinglan;Bear Brian;Miller Mark T.;McCartney Jason;Numa Mehdi Michel Jamel;Yang Xiaoqing
分类号 A61K31/496;A61K31/4523;A61K31/4525;A61K31/453;A61K31/454;A61K31/4427;A61K31/443;A61K31/4433;A61K31/4439;A61K31/41;A61K31/4178;A61K31/4184;A61K31/4192;A61K31/404;C07D471/04;C07D405/12;G01N33/50;C07D403/12;C07D403/14;C07D401/14;C07D211/00;C07D235/04;C07D257/02;C07D249/04;C07D487/00;C07D405/02;C07D405/14 主分类号 A61K31/496
代理机构 Honigman Miller Schwartz and Cohn LLP 代理人 Honigman Miller Schwartz and Cohn LLP ;Berven Heidi;O'Brien Jonathan P.
主权项 1. A method of treating or lessening the severity of pancreatic insufficiency or male infertility in a patient, comprising the step of administering to said patient an effective amount of a compound of the formula:or a pharmaceutically acceptable salt thereof, wherein R1 is —ZAR4, wherein each ZA is independently a bond or an optionally substituted branched or straight C1-6 aliphatic chain wherein up to two carbon units of ZA are optionally and independently replaced by —CO—, —CS—, —CONRA—, —CONRANRA—, —CO2—, —OCO—, —NRACO2—, —O—, —NRACONRA—, —OCONRA—, —NRANRA—, —NRACO—, —S—, —SO—, —SO2—, —NRA—, —SO2NRA—, —NRASO2—, or —NRASO2NRA—, Each R4 is independently RA, halo, —OH, —NH2, —NO2, —CN, or —OCF3,Each RA is independently hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl; Each R2 is independently —ZBR5, wherein each ZB is independently a bond or an optionally substituted branched or straight C1-6 aliphatic chain wherein up to two carbon units of ZB are optionally and independently replaced by —CO—, —CS—, —CONRB—, —CONRBNRB—, —CO2—, —OCO—, —NRBCO2—, —O—, —NRBCONRB—, —OCONRB—, —NRBNRB—, —NRBCO—, —S—, —SO—, —SO2—, —NRB—, —SO2NRB—, —NRBSO2—, or —NRBSO2NRB—, Each R5 is independently RB, halo, —OH, —NH2, —NO2, —CN, —CF3, or —OCF3,Each RB is independently hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl, Or, any two adjacent R2 groups together with the atoms to which they are attached form an optionally substituted carbocycle or an optionally substituted heterocycle; Ring A is an optionally substituted 3-7 membered monocyclic ring having 0-3 heteroatoms selected from N, O, and S; Ring B is a group having formula Ia: or a pharmaceutically acceptable salt thereof, whereinp is 0-2,Each R3 and R′3 is independently —ZCR6, where each ZC is independently a bond or an optionally substituted branched or straight C1-6 aliphatic chain wherein up to two carbon units of ZC are optionally and independently replaced by —CO—, —CS—, —CONRC—, —CONRCNRC—, —CO2—, —OCO—, —NRCCO2—, —O—, —NRCCONRC—, —OCONRC—, —NRCNRC—, —NRCCO—, —S—, —SO—, —SO2—, —NRC—, —SO2NRC—, —NRCSO2—, or —NRCSO2NRC—, Each R6 is independently RC, halo, —OH, —NH2, —NO2, —CN, or —OCF3,Each RC is independently hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl, Or, any two adjacent R3 groups together with the atoms to which they are attached form an optionally substituted heterocycle; and n is 1-3.
地址 Boston MA US