Modulators of atp-binding cassette transporters

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar1 is a 5-6 membered aromatic monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is optionally fused to a 5-12 membered monocyclic or bicyclic, aromatic, partially unsaturated, or saturated ring, wherein each ring contains 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein Ar1 has m substituents each independently selected from —WRW;
• 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′—, —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′—;
• RW is independently R′, halo, NO2, CN, CF3, or OCF3;
• m is 0-5;
• each of R1, R2, R3, R4, and R5 is independently —X—RX;
• X is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of X 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—, or —NR′SO2NR′—;
• RX is independently R′, halo, NO2, CN, CF3, or OCF3;
• R6 is hydrogen, CF3, —OR′, —SR′, or an optionally substituted C1-8 aliphatic group;
• R7 is hydrogen or a C1-6 aliphatic group optionally substituted with —X—RX;
• 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;
• provided that:
• i) when R1, R2, R3, R4, R5, R6 and R7 are hydrogen, then Ar1 is not phenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2-methylphenyl, 2,6-dichlorophenyl, 2,4-dichlorophenyl, 2-bromophenyl, 4-bromophenyl, 4-hydroxyphenyl, 2,4-dinitrophenyl, 3,5-dicarboxylic acid phenyl, 2,4-dimethylphenyl, 2,6-dimethylphenyl, 2-ethylphenyl, 3-nitro-4-methylphenyl, 3-carboxylic-acid phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-trifluoromethylphenyl, 3-ethoxyphenyl, 4-chlorophenyl, 3-methoxyphenyl, 4-dimethylaminophenyl, 3,4-dimethylphenyl, 2-ethylphenyl, or 4-ethoxycarbonylphenyl;
• ii) when R1, R2, R3, R5, R6 and R7 are hydrogen, and R4 is methoxy, then Ar1 is not 2-fluorophenyl or 3-fluorophenyl;
• iii) when R1, R3, R4, R5, R6 and R7 are hydrogen, R2 is 1,2,3,4-tetrahydroisoquinolin-1-yl-sulfonyl, then Ar1 is not 3-trifluoromethylphenyl;
• iv) when R1, R2, R3, R4, R5 and R7 are hydrogen, R6 is methyl, then Ar1 is not phenyl;
• v) when R1, R4, R5, R6 and R7 are hydrogen, R2 and R3, taken together, are methylenedioxy, then Ar1 is not 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-carboethoxyphenyl, 6-ethoxy-benzothiazol-2-yl, 6-carboethoxy-benzothiazol-2-yl, 6-halo-benzothiazol-2-yl, 6-nitro-benzothiazol-2-yl, or 6-thiocyano-benzothiazol-2-yl.
• vi) when R1, R4, R5, R6 and R7 are hydrogen, R2 and R3, taken together, are methylenedioxy, then Ar1 is not 4-substituted phenyl wherein said substituent is —SO2NHRxx, wherein Rxx is 2-pyridinyl, 4-methyl-2-pyrimidinyl, 3,4-dimethyl-5-isoxazolyl;
• vii) when R1, R2, R3, R4, R5, R6, and R7 are hydrogen, then Ar1 is not thiazol-2-yl, 1H-1,2,4-triazol-3-yl, or 1H-1,3,4-triazol-2-yl;
• viii) when R1, R2, R3, R5, R6, and R7 are hydrogen, and R4 is CF3, OMe, chloro, SCF3, or OCF3, then Ar1 is not 5-methyl-1,2-oxazol-3-yl, thiazol-2-yl, 4-fluorophenyl, pyrimidin-2-yl, 1-methyl-1,2-(1H)-pyrazol-5-yl, pyridine-2-yl, phenyl, N-methyl-imidazol-2-yl, imidazol-2-yl, 5-methyl-imidazol-2-yl, 1,3-oxazol-2-yl, or 1,3,5-(1H)-triazol-2-yl;
• ix) when R1, R2, R3, R4, R5, R6, and R7 each is hydrogen, then Ar1 is not pyrimidin-2-yl, 4,6-dimethyl-pyrimidin-2-yl, 4-methoxy-6-methyl-1,3,5-triazin-2-yl;
• 5-bromo-pyridin-2-yl, pyridin-2-yl, or 3,5-dichloro-pyridin-2-yl;
• x) when R1, R2, R3, R4, R5 and R7 each is hydrogen, R6 is hydroxy, then Ar1 is not 2,6-dichloro-4-aminosulfonyl-phenyl;
• xi) when R2 or R3 is an optionally substituted N-piperazyl, N-piperidyl, or N-morpholinyl, then Ar1 is not an optionally substituted ring selected from thiazol-2-yl, pyridyl, phenyl, thiadiazolyl, benzothiazol-2-yl, or indazolyl;
• xii) when R2 is optionally substituted cyclohexylamino, then Ar1 is not optionally substituted phenyl, pyridyl, or thiadiazolyl;
• xiii) Ar1 is not optionally substituted tetrazolyl;
• xiv) when R2, R4, R5, R6, and R7 each is hydrogen, and R1 and R3 both are simultaneously CF3, chloro, methyl, or methoxy, then Ar1 is not 4,5-dihydro-1,3-thiazol-2-yl, thiazol-2-yl, or [3,5-bis(trifluoromethyl)-1H-1-pyrazol-1-yl]phenyl;
• xv) when R1, R4, R5, R6, and R7 each is hydrogen, and Ar1 is thiazol-2-yl, then neither R2 nor R3 is isopropyl, chloro, or CF3;
• xvi) when Ar1 is 4-methoxyphenyl, 4-trifluoromethylphenyl, 2-fluorophenyl, phenyl, or 3-chlorophenyl, then:
• a) when R1, R2, R4, R5, R6, and R7 each is hydrogen, then R3 is not methoxy;
• or
• b) when R1, R3, R4, R5, R6, and R7 each is hydrogen, then R2 is not chloro;
• or
• c) when R1, R2, R3, R5, R6, and R7 each is hydrogen, then R4 is not methoxy;
• or
• d) when R1, R3, R4, R6, and R7 each is hydrogen, and R5 is ethyl, then R2 is not chloro;
• e) when R1, R2, R4, R5, R6, and R7 each is hydrogen, then R3 is not chloro;
• xvi) when R1, R3, R4, R5, R6, and R7 each is hydrogen, and R2 is CF3 or OCF3, then Ar1 is not [3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl;
• xvii) when R1, R2, R4, R5, R6, and R7 each is hydrogen, and R3 is hydrogen or CF3, then Ar1 is not a phenyl substituted with —OCH2CH2Ph, —OCH2CH2(2-trifluoromethyl-phenyl), —OCH2CH2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl), or substituted 1H-pyrazol-3-yl;
• and
• xviii) the following two compounds are excluded: