Modulators of ATP-binding cassette transporters

A method of treating a condition, disease, or disorder in a patient implicated by CFTR transporter activity wherein the condition, disease, or disorder is cystic fibrosis, comprising the step of administering to said patient a compound having formula IIIB:

• wherein:
• X9 is CH2, CF2, CH2—CH2, or CF2—CF2;
• m is 0 to 4;
• Ht1 is a 5-membered heteroaromatic ring containing 1-4 heteroatoms selected from O, S, N, or NH;
• x, q, and z is independently 0-5;
• Q-RQ, X—Rx and Z—RZ each is independently R′;
• L is a bond, O, S, SO, SO2, C(O), NR′, C1-4 aliphatic, or CHRL;
• RL is —OR′, —SR′, —SOR′, —SO2R′, or —N(R′)2;
• or
• L is
• wherein ring A′ is a 3-7 membered monocyclic ring having 0-3 heteroatoms selected from O, S, N, or NH, wherein ring A′ is optionally substituted with q occurrences of -QRQ;
• Ar is phenyl or a six-membered heteroaromatic ring;
• R′ is independently selected from hydrogen or an optionally substituted group selected from a C1-C8 aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of R′ are taken together with the atom(s) to which they are bound to form an optionally substituted 3-12 membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or
• R′ is independently R1, R2, R3, R4, or R5;
• R1 is oxo, R6 or ((C1-C4)aliphatic)n-Y;
• or two R1 on adjacent ring atoms, taken together, form 1,2-methylenedioxy, 1,2-difluoromethylenedioxy, 1,2-ethylenedioxy, or 1,2-tetrafluoroethylenedioxy;
• n is 0 or 1;
• Y is halo, CN, NO2, CF3, OCF3, OH, SR6, S(O)R6, SO2R6, NH2, NHR6, N(R6)2, NR6R8, COOH, COOR6 or OR6;
• R2 is aliphatic, wherein each R2 optionally comprises up to 2 substituents independently selected from R1, R4, or R5;
• R3 is a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring optionally comprising up to 3 substituents, independently selected from R1, R2, R4 or R5;
• R4 is OR5, OR6, OC(O)R6, OC(O)R5, OC(O)OR6, OC(O)OR5, OC(O)N(R6)2, OC(O)N(R5)2, OC(O)N(R6R5), SR6, SR5, S(O)R6, S(O)R5, SO2R6, SO2R5, SO2N(R6)2, SO2N(R5)2, SO2NR5R6, SO3R6, SO3R5, C(O)R5, C(O)OR5, C(O)R6, C(O)OR6, C(O)N(R6)2, C(O)N(R5)2, C(O)N(R5R6), C(O)N(OR6)R6, C(O)N(OR5)R6, C(O)N(OR6)R5, C(O)N(OR5)R5, C(NOR6)R6, C(NOR6)R5, C(NOR5)R6, C(NOR5)R5, N(R6)2, N(R5)2, N(R5R6), NR5C(O)R5, NR6C(O)R6, NR6C(O)R5, NR5C(O)R6, NR6C(O)OR6, NR5C(O)OR6, NR6C(O)OR5, NR5C(O)OR5, NR6C(O)N(R6)2, NR6C(O)NR5R6, NR6C(O)N(R5)2, NR5C(O)N(R6)2, NR5C(O)NR5R6, NR5C(O)N(R5)2, NR6SO2R6, NR6SO2R5, NR5SO2R6NR5SO2R5, NR6SO2N(R6)2, NR6SO2NR5R6, NR6SO2N(R5)2, NR5SO2N(R6)2, NR5SO2NR5R6, NR5SO2N(R5)2, N(OR6)R6, N(OR6)R5, N(OR5)R5, or N(OR5)R6;
• R5 is a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, optionally comprising up to 3 R1 substituents;
• R6 is H or aliphatic, wherein R6 optionally comprises a R7 substituent;
• R7 is a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, and each R7 optionally comprises up to 2 substituents independently chosen from H, (C1-C6)-straight or branched alkyl, (C2-C6) straight or branched alkenyl or alkynyl, 1,2-methylenedioxy, 1,2-ethylenedioxy, or (CH2)n—Z′;
• Z′ is selected from halo, CN, NO2, CF3, OCF3, OH, S-aliphatic, S(O)-aliphatic, SO2-aliphatic, NH2, NH-aliphatic, N(aliphatic)2, N(aliphatic)R8, NHR8, COOH, C(O)O(-aliphatic), or O-aliphatic;
• and
• R8 is an amino protecting group.