Claims for Patent: 11,639,347

Summary for Patent: 11,639,347

Title:	Modulators of ATP-binding cassette transporters
Abstract:	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.
Inventor(s):	Sara S. Hadida Ruah, Peter D. J. Grootenhuis, Fredrick Van Goor, Jinglan Zhou, Brian Bear, Mark T. Miller, Jason McCartney, Mehdi Michel Jamel Numa, Xiaoqing Yang
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US17/181,931
Patent Claims:	1. A compound of formula IIc: 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—; and each R4 is independently RA, halo, —OH, —NH2, —NO2, —CN, or —OCF3; and wherein each RA is independently selected from hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, and an optionally substituted heteroaryl; each R2 is —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—; and each R5 is independently selected from RB, halogen, —OH, —NH2, —NO2, —CN, CF3, and —OCF3; and wherein each RB is independently selected from hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, and an optionally substituted heteroaryl; or wherein any two adjacent R2 groups, together with the atoms to which they are attached, form an optionally substituted carbocycle or an optionally substituted heterocycle; and each R3 and R′3 is independently —ZCR6; wherein 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 selected from RC, halogen, —OH, —NH2, —NO2, —CN, and —OCF3; and wherein each RC is independently selected from hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, and an optionally substituted heteroaryl; or wherein any two adjacent R3 groups, together with the atoms to which they are attached, form an optionally substituted carbocycle or an optionally substituted heterocycle; n is 1-3; and p is 0-3. 2. A compound of formula IId: or a pharmaceutically acceptable salt thereof; wherein: both R2 groups, together with the atoms to which they are attached, form a group selected from: R′3 is independently selected from: each R3 is independently selected from —H, —CH3, —CH2OH, —CH2CH3, —CH2CH2OH, —CH2CH2CH3, —NH2, halo, —OCH3, —CN, —CF3, —C(O)OCH2CH3, —S(O)2OCH3, —CH2NH2, —C(O)NH2, 3. A compound according to claim 2, wherein both R2 groups, together with the atoms to which they are attached, is selected from the groups: 4. A compound according to claim 3, wherein R′3 is hydrogen or the group: wherein R31 is H or a C1-2 aliphatic that is optionally substituted with 1-3 halogen, —OH, or combinations thereof; R32 is -L-R33; and wherein L is a bond, —CH2—, —CH2O—, —CH2NHS(O)2, —CH2C(O)—, —CH2NHC(O)—, or —CH2NH—; and R33 is hydrogen, C1-2 aliphatic, cycloaliphatic, heterocycloaliphatic, or heteroaryl, each of which is optionally substituted with one of —OH, —NH2, or —CN. 5. A compound according to claim 4, wherein R31 is hydrogen and R32 is C1-2 aliphatic optionally substituted with one of —OH, NH2, or —CN. 6. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. 7. A pharmaceutical composition according to claim 6, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents. 8. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 5, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. 9. A pharmaceutical composition according to claim 8, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents. 10. A method of treating or lessening the severity of cystic fibrosis in a patient, comprising the step of administering to a patient an effective amount of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4. 11. A method of treating or lessening the severity of cystic fibrosis in a patient, comprising the step of administering to a patient an effective amount of a compound or a pharmaceutically acceptable salt thereof according to claim 5.