Modulators of atp-binding cassette transporters

A kit for use in measuring the activity of a ABC transporter or a fragment thereof in a biological sample in vitro or in vivo, comprising:

• (i) a composition comprising 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;
• wherein each occurrence of WRW is selected from halo, cyano, CF3, CHF2, OCHF2, Me, Et, CH(Me)2, CHMeEt, n-propyl, t-butyl, OMe, OEt, OPh, O-fluorophenyl, O-difluorophenyl, O-methoxyphenyl, O-tolyl, O-benzyl, SMe, SCF3, SCHF2, SEt, CH2CN, NH2, NHMe, N(Me)2, NHEt, N(Et)2, C(O)CH3, C(O)Ph, C(O)NH2, SPh, SO2-(amino-pyridyl), SO2NH2, SO2Ph, SO2NHPh, SO2—N-morpholino, SO2—N-pyrrolidyl, N-pyrrolyl, N-morpholino, 1-piperidyl, phenyl, benzyl, (cyclohexyl-methylamino)methyl, 4-Methyl-2,4-dihydro-pyrazol-3-one-2-yl, benzimidazol-2yl, furan-2-yl, 4-methyl-4H-[1,2,4]triazol-3-yl, 3-(4′-chlorophenyl)-[1,2,4]oxadiazol-5-yl, NHC(O)Me, NHC(O)Et, NHC(O)Ph, 2-indolyl, 5-indolyl, —CH2CH2OH, —OCF3, O-(2,3-dimethylphenyl), 5-methylfuryl, —SO2—N-piperidyl, 2-tolyl, 3-tolyl, 4-tolyl, O-butyl, NHCO2C(Me)3, CO2C(Me)3, isopropenyl, n-butyl, O-(2,4-dichlorophenyl), NHSO2PhMe, O-β-chloro-5-trifluoromethyl-2-pyridyl), phenylhydroxymethyl, 2,5-dimethylpyrrolyl, NHCOCH2C(Me)3, O-(2-tert-butyl)phenyl, 2,3-dimethylphenyl, 3,4-dimethylphenyl, 4-hydroxymethyl phenyl, 4-dimethylaminophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-cyanomethylphenyl, 4-isobutylphenyl, 3-pyridyl, 4-pyridyl, 4-isopropylphenyl, 3-isopropylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-methylenedioxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-methylthiophenyl, 4-methylthiophenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4-dimethoxyphenyl, 5-chloro-2-methoxyphenyl, 2-OCF3-phenyl, 3-trifluoromethoxy-phenyl, 4-trifluoromethoxyphenyl, 2-phenoxyphenyl, 4-phenoxyphenyl, 2-fluoro-3-methoxy-phenyl, 2,4-dimethoxy-5-pyrimidyl, 5-isopropyl-2-methoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-cyanophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-difluorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3-chloro-4-fluoro-phenyl, 3,5-dichlorophenyl, 2,5-dichlorophenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 2,4-dichlorophenyl, 3-methoxycarbonylphenyl, 4-methoxycarbonyl phenyl, 3-isopropyloxycarbonylphenyl, 3-acetamidophenyl, 4-fluoro-3-methylphenyl, 4-methanesulfinyl-phenyl, 4-methanesulfonyl-phenyl, 4-N-(2-N,N-dimethylaminoethyl)carbamoylphenyl, 5-acetyl-2-thienyl, 2-benzothienyl, 3-benzothienyl, furan-3-yl, 4-methyl-2-thienyl, 5-cyano-2-thienyl, N′-phenylcarbonyl-N-piperazinyl, —NHCO2Et, —NHCO2Me, N-pyrrolidinyl, —NHSO2(CH2)2 N-piperidine, —NHSO2(CH2)2 N-morpholine, —NHSO2(CH2)2N(Me)2, COCH2N(Me)COCH2NHMe, —CO2Et, O-propyl, —CH2CH2NHCO2C(Me)3, hydroxy, aminomethyl, pentyl, adamantyl, cyclopentyl, ethoxyethyl, C(Me)2CH2OH, C(Me)2CO2Et, —CHOHMe, CH2CO2Et, —C(Me)2CH2NHCO2C(Me)3, O(CH2)2OEt, O(CH2)2OH, CO2Me, hydroxymethyl, 1-methyl-1-cyclohexyl, 1-methyl-1-cyclooctyl, 1-methyl-1-cycloheptyl, C(Et)2C(Me)3, C(Et)3, CONHCH2CH(Me)2, 2-aminomethyl-phenyl, ethenyl, 1-piperidinylcarbonyl, ethynyl, cyclohexyl, 4-methylpiperidinyl, —OCO2Me, —C(Me)2CH2NHCO2CH2CH(Me)2, —C(Me)2CH2NHCO2CH2CH2CH3, —C(Me)2CH2NHCO2Et, —C(Me)2CH2NHCO2Me, —C(Me)2CH2NHCO2CH2C(Me)3, —CH2NHCOCF3, —CH2NHCO2C(Me)3, —C(Me)2CH2NHCO2(CH2)3CH3, C(Me)2CH2NHCO2(CH2)2OMe, C(OH) (CF3)2, —C(Me)2CH2NHCO2CH2-tetrahydrofuran-3-yl, C(Me)2CH2O(CH2)2OMe, or 3-ethyl-2,6-dioxopiperidin-3-yl;
• 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 C1-6 aliphatic group;
• R7 is hydrogen;
• 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 the following compounds of FIG. 1 are excluded:
• and
• (ii) instructions for:
• a) contacting the composition with the biological sample;
• and
• b) measuring activity of said ABC transporter or a fragment thereof.