Modulators of ATP-binding cassette transporters

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• G1 is ═O, ORA, SRA, or NRARB, wherein RA and RB are each independently V—RV, or RA and RB, taken together with the nitrogen atom, 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, wherein V is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of V are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR′—, —CONR′NR′—, —CO2—, —OCO—, —NR′CO2—, —O—, —NR′CONR′—, —OCONR′—, —NR′NR′, —NR′NR′CO—, —NR′CO—, —S—, —SO, —SO2—, —NR′—, —SO2NR′—, NR′SO2—, —NR′SO2NR′—, and each occurrence of RV is independently R′, halogen, NO2, or CN, and wherein RA and RB, or any ring formed by RA and RB taken together with the nitrogen atom, are optionally and independently substituted by q occurrences of U—RU, wherein q is 0-5, U is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of U are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR′—, —CONR′NR′—, —CO2—, —OCO—, —NR′CO2—, —O—, —NR′CONR′—, —OCONR′—, —NR′NR′, —NR′NR′CO—, —NR′CO—, —S—, —SO, —SO2—, —NR′—, —SO2NR′—, —NR′SO2—, —NR′SO2NR′—, and each occurrence of RU is independently R′, halogen, NO2, or CN;
• R1 is absent or is Y—RY;
• wherein Y is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of Y are optionally and independently replaced by —CO—, —CONR—, —O—, —NRCO—, —S—, —SO2—, —NR—, —SO2NR—, or —NRSO2—, and each occurrence of RY is independently R′, OR′, SR′, N(R′)2, halogen, NO2, or CN, provided that when R1 is present, it is always bonded to the nitrogen atom through a carbon atom;
• each occurrence of R is independently selected from hydrogen or an optionally substituted C1-8 aliphatic group;
• and each occurrence of 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′, 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;
• R2 and R3, taken together, form a ring selected from:
• with x independent occurrences of Q-RX, wherein x is 0-5;
• Q is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of Q are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR—, —CONRNR—, —CO2—, —OCO—, —NRCO2—, —O—, —NRCONR—, —OCONR—, —NRNR, —NRNRCO—, —NRCO—, —S—, —SO, —SO2—, —NR—, —SO2NR—, —NRSO2—, —NRSO2NR—, and each occurrence of RX is independently R′, halogen, NO2, or CN;
• L is G2-B-G3-Ar1,
• wherein G2 is absent, an optionally substituted C1-C6 alkylidene chain, or a C3-C6 spirocycloalkylidene ring, wherein one or two methylene units in said alkylidene are optionally and independently replaced with —CO—, —CS—, —SO—, —SO2—, —NR′—, N(SO2R′)—, N(COR′)—, —O—, or —S—, and wherein one or two hydrogen atoms of one or more methylene units are optionally substituted with R′;
• G3 is —NR′—, —CO—, or —SO2—;
• B is an optionally substituted 5-, 6- or 7-membered saturated, partially unsaturated or fully unsaturated ring having the structure
• wherein n is 0, 1, or 2;
• X2 and X5 are each N;
• and each occurrence of X1, when present, and X3, X4 and X6 are each independently, as valency and stability permit, C(R′)2, —O—, —NR—, S, C═O, or C═S;
• and
• Ar1 is 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;
• wherein Ar1 is optionally substituted with m independent occurrences of WRW, wherein m is 0-5 and W is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of W are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR—, —CONRNR—, —CO2—, —OCO—, —NRCO2—, —O—, —NRCONR—, —OCONR—, —NRNR, —NRNRCO—, —NRCO—, —S—, —SO, —SO2—, —NR—, —SO2NR—, —NRSO2—, —NRSO2NR—, and each occurrence of RW is independently R′, halogen, NO2, or CN.