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    1-(BENZO [D] [1,3] DI0X0L-5-YL) -N- (PHENYL) CYCLOPROPANE- CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS FOR THE TREATMENT OF CYSTIC FIBROSIS
    19.
    发明申请
    1-(BENZO [D] [1,3] DI0X0L-5-YL) -N- (PHENYL) CYCLOPROPANE- CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS FOR THE TREATMENT OF CYSTIC FIBROSIS 审中-公开
    1-（BENZO [D] [1,3] DI0X0L-5-YL）-N-（苯基）环丙烷 - 羧酰胺衍生物和相关化合物作为ATP-结合CASSETTE运输机用于治疗CYSTIC FIBROSIS的调节剂

    公开(公告)号：WO2007087066A3

    公开(公告)日：2007-10-25

    申请号：PCT/US2006049412

    申请日：2006-12-28

    Applicant: VERTEX PHARMA ,  RUAH SARA S HADIDA ,  MILLER MARK T ,  BEAR BRIAN ,  MCCARTNEY JASON ,  GROOTENHUIS PETER D J

    Inventor： RUAH SARA S HADIDA ,  MILLER MARK T ,  BEAR BRIAN ,  MCCARTNEY JASON ,  GROOTENHUIS PETER D J

    IPC: C07D317/68 ,  A61K31/36 ,  A61P11/00

    CPC classification number: C07D498/04 ,  A61K31/167 ,  A61K31/357 ,  A61K31/381 ,  A61K31/40 ,  A61K31/437 ,  A61K31/443 ,  A61K31/519 ,  A61K31/538 ,  A61K45/06 ,  C07C235/16 ,  C07D207/48 ,  C07D317/54 ,  C07D317/60 ,  C07D317/68 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/04 ,  C07D487/04

    Abstract: A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: Each R1 is independently an optionally substituted C 1-6 aliphatic, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted C 3-10 membered cycloaliphatic or an optionally substituted 4 to 10 membered heterocycloaliphatic, carboxy, amido, amino, halo, or hydroxy, provided that at least one R 1 is an optionally substituted aryl or an optionally substituted heteroaryl and said R 1 is attached to the 3- or 4- position of the phenyl ring; R 2 is hydrogen, an optionally substituted C 1-6 aliphatic, an optionally substituted C 3-6 cycloaliphatic, an optionally substituted phenyl, or an optionally substituted heteroaryl; Ring A is an optionally substituted cycloaliphatic or an optionally substituted heterocycloaliphatic where the atoms of ring A adjacent to C* are carbon atoms; Each R 4 is an optionally substituted aryl or an optionally substituted heteroaryl; and n is 1, 2, 3, 4, or 5. 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.

    Abstract translation: 式（I）化合物或其药学上可接受的盐，其中：每个R 1独立地为任选取代的C 1-6脂族基，任选取代的芳基，任选取代的杂芳基，任选取代的C 3-10元环脂族或任选取代的4至10元杂环脂族，羧基，酰胺基，氨基，卤素或羟基，条件是至少一个R 1可以是任选的 取代的芳基或任选取代的杂芳基，并且所述R 1连接在苯环的3-或4-位上; R 2是氢，任选取代的C 1-6脂族基，任选取代的C 3-6脂环族基，任选取代的苯基，或 任选取代的杂芳基; 环A是任选取代的脂环族或任选取代的杂环脂族基，其中与C *相邻的环A的原子是碳原子; 每个R 4是任选取代的芳基或任选取代的杂芳基; 和n为1,2,3,4或5.本发明化合物及其药学上可接受的组合物可用作ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜电导调节剂 （ “CFTR”）。 本发明还涉及使用本发明化合物治疗ABC转运蛋白介导的疾病的方法。

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