Modulators of ATP-Binding Cassette transporters

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

• or a pharmaceutically acceptable salt thereof;
• wherein:
• X1 is a bond, O, S, CF2, CH2, or NR;
• R is H or R2
• A1 is aryl, or heteroaryl;
• each B1 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 A1 or B1 is optionally substituted with up to 4 substituents independently selected from R1, R2, R3, R4, or R5;
• each B1 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 A1 is optionally substituted with up to 4 substituents independently selected from R1, R2, R3, R4, or R5;
• R1 is R6 or ((C1-C4)aliphatic)n-Y;
• n is 0 or 1;
• Y is halo, CN, CF3, OCF3, OH, NH2, NHR6, N(R6)2, COOH, COOR6 or OR6;
• or
• two R1 on adjacent ring atoms, taken together, form 1,2-methylenedioxy or 1,2-ethylenedioxy;
• R2 is aliphatic, wherein each R2 is optionally substituted with up to 2 substituents independently selected from R1, R4, or R5;
• R3 is a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring optionally substituted with up to 3 substituents, independently selected from R1, R2, R4 or R5;
• R4 is OR5, C(O)R5, C(O)OR5, C(O)R6, C(O)OR6, C(O)N(R6)2, C(O)N(R5)2, or C(O)N(R5R6);
• R5 is a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, optionally substituted with up to 3 R1 substituents;
• and
• R6 is H or aliphatic;
• provided that for compounds of formula (II):
• (i) when both B1 are simultaneously phenyl and X1 is CH2, then A1 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 X1 is a bond, then A1 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 X1 is a bond, one B1 is phenyl and the other B1 is N-piperidyl, then A1 is not:
• (ii) when X1 is a bond, then A1 is not an optionally substituted 6-membered heteroaryl ring with 1-3 nitrogen ring atoms.