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.

主权项

1. A method of activating Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activity comprising the step of contacting the CFTR with a compound of formula I: or a pharmaceutically acceptable salt thereof; wherein, independently for each occurrence: R1 and R2 are —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—; or any two adjacent R2 groups together with the atoms to which they are attached form an optionally substituted carbocycle or optionally substituted heterocycle; R4 is independently RA, halo, —OH, —NH2, —NO2, —CN, or —OCF3; 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; ring A is an optionally substituted 3-7 membered monocyclic ring having 0-3 heteroatoms selected from N, O, and S; n is and integer from 1 to 3 inclusive; ring B is wherein:p is 2 or 3; andR3 is C1-C6 aliphatic or halo, and;R′3 is —ZCR6, whereZC is 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—;R6 is RC, halo, —OH, —NH2, —NO2, —CN, or —OCF3;RC is hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, or an optionally substituted heteroaryl;and wherein when one of the 2 or 3 R3 is adjacent to R′3 and the adjacent R3 is C1-C6 aliphatic, then R′3 and the adjacent R3, together with the atoms to which they are attached, form an optionally substituted heterocycle.