MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
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.
1 .- 28 . (canceled)
29 . A compound of formula II:
or a pharmaceutically acceptable salt thereof, wherein independently for each occurrence:
R is H, OH, OCH 3 , or two R taken together form —OCH 2 O— or —OCF 2 O—;
R 1 is H or alkyl;
R 2 is H or F;
R 3 is H or CN;
R 4 is —CH 2 CH 2 N + (CH 3 ) 3 ; and
R 5 is H, OH, —CH 2 OCH 2 CH(OH)CH 2 OH, —CH 2 OH, or R 4 and R 5 taken together form a five-membered ring.
30 . A compound of formula IIa:
or a pharmaceutically acceptable salt thereof, wherein:
R 4 is —CH 2 CH 2 N + (CH 3 ) 3 ; and
R 5 is H, OH, —CH 2 OCH 2 CH(OH)CH 2 OH, —CH 2 OH, or R 4 and R 5 taken together form a five-membered ring.
31 . A pharmaceutically acceptable salt according to claim 29 or 30 having the following formula:
32 . A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 29 or 30 and a pharmaceutically acceptable carrier.
33 . The pharmaceutical composition of claim 32 , wherein the pharmaceutical composition further comprises an additional agent selected from a mucolytic agent, a bronchodilator, an antibiotic, an anti-infective, an anti-inflammatory agent, a CFTR corrector, a CFTR potentiator, or a nutritional agent.
34 . The pharmaceutical composition of claim 33 , wherein the additional agent is N-(5-hydroxy-2,4-di-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide.