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.

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.