Modulators of ATP-Binding Cassette transporters

1. A compound having formula (II) or formula (III):

or a pharmaceutically acceptable salt thereof;

wherein:

X 1 is a bond, O, S, CF 2 , CH 2 , or NR;

R is H or R 2

A 1 is aryl, or heteroaryl;

each B 1 is independently selected from a 3-7 membered monocyclic, saturated, unsaturated or aryl ring containing 0-4 heteroatoms selected from N, S, or O;

wherein each A 1 or B 1 is optionally substituted with up to 4 substituents independently selected from R1, R2, R3, R4, or R5;

each B 1 is independently selected from 3-7 membered monocyclic, saturated, unsaturated or aromatic ring containing 0-4 heteroatoms selected from N, NH, S, or O;

wherein each A 1 is optionally substituted with up to 4 substituents independently selected from R 1 , R 2 , R 3 , R 4 , or R 5 ;

R 1 is R 6 or ((C1-C4)aliphatic) n -Y;

n is 0 or 1;

Y is halo, CN, CF 3 , OCF 3 , OH, NH 2 , NHR 6 , N(R 6 ) 2 , COOH, COOR 6 or OR 6 ; or

two R 1 on adjacent ring atoms, taken together, form 1,2-methylenedioxy or 1,2-ethylenedioxy;

R 2 is aliphatic, wherein each R 2 is optionally substituted with up to 2 substituents independently selected from R 1 , R 4 , or R 5 ;

R 3 is a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring optionally substituted with up to 3 substituents, independently selected from R 1 , R 2 , R 4 or R 5 ;

R 4 is OR 5 , C(O)R 5 , C(O)OR 5 , C(O)R 6 , C(O)OR 6 , C(O)N(R 6 ) 2 , C(O)N(R 5 ) 2 , or C(O)N(R 5 R 6 );

R 5 is a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, optionally substituted with up to 3 R 1 substituents; and

R 6 is H or aliphatic;

provided that for compounds of formula (II):

(i) when both B 1 are simultaneously phenyl and X 1 is CH 2 , then A 1 is not 4-fluoro-phenyl, 4-phenyl-piperidyl, phenyl, 2,4-dichloro-phenyl, 4-methoxy-phenyl, 3,4-dichloro-phenyl, 2,5-dichloro-phenyl, 4-nitro-phenyl, 4-bromo-phenyl, 4-methyl-phenyl, 2-chloro-phenyl, 1-naphthyl, 3-trifluoromethyl-phenyl, 2,3-dichlorophenyl, N-morpholinyl, 4-chloro-phenyl, 3-chloro-phenyl, or 3-nitro-phenyl; and

(ii) when X 1 is a bond, then A 1 is not an optionally substituted 6-membered heteroaryl ring with 1-3 nitrogen ring atoms; and

provided that for compounds of formula (III):

(i) when X 1 is a bond, one B 1 is phenyl and the other B 1 is N-piperidyl, then A 1 is not:

(ii) when X 1 is a bond, then A 1 is not an optionally substituted 6-membered heteroaryl ring with 1-3 nitrogen ring atoms.

2. The compound according to claim 1 , wherein X 1 is CH 2 , CF 2 , or O.

3. The compound according to claim 1 , wherein X 1 is CH 2 .

4. The compound according to claim 1 , wherein A 1 is selected from phenyl, triazinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyridyl, pyrazolyl, quinolinyl, isoquinolinyl, or naphthyl.

5. The compound according to claim 1 , wherein each B 1 is independently an optionally substituted phenyl or naphthyl.

6. The compound according to claim 1 , wherein each B 1 is an unsubstituted phenyl.

7. The compound according to claim 1 , wherein each B 1 is independently selected from optionally substituted C5-C7 heteroaryl.

8. The compound according to claim 7 , wherein each B 1 is independently selected from optionally substituted pyrazolyl or imidazolyl.

9. The compound according to claim 1 , wherein B 1 is selected from optionally substituted pyrrolinyl, pyrazolinyl, piperidinyl, morpholinyl, or piperazinyl.

10. The compound according to claim 1 , wherein A 1 is optionally substituted C6-C 10 aryl ring.

11. The compound according to claim 10 , wherein A 1 is optionally substituted phenyl or naphthyl.

12. The compound according to claim 1 , wherein A 1 is optionally substituted C5-C12 heteroaryl ring.

13. The compound according to claim 12 , wherein A 1 is pyridinyl.

14. The compound according to claim 1 , wherein each B 1 is independently an optionally substituted 3-7 membered heterocyclic ring having up to 4 heteroatoms selected from O, S, or N.

15. The compound according to claim 14 , wherein each B 1 is independently selected from optionally substituted pyrrolidyl, pyrrolidinyl, pyranyl, piperidinyl, or morpholinyl.