Bis-aryl sulfonamides

A modulator of the formula (I) or a salt or N-oxide thereof:

• L is —C(O)—, —S—, —S(O)— or —S(O)2-;
• X represents from 1 to 5 substituents independently selected from the group consisting of halogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, —CN, —NO2, —C(O)R1, —CO2R1, —C(O)NR1R2, —OR1, —OC(O)R1, —OC(O)NR1R2, —NO2, —NR3C(O)R1, —NR3C(O)NR1R2, —NR1R2, —NR3CO2R1, —NR3S(O)2R1, —SR1, —S(O)R1, —S(O)2R1, —S(O)2NR1R2, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl;
• substituted C1-8 alkyl, substituted C2-8 alkenyl, or substituted C2-8 alkynyl may have from 1-5 substituents independently selected from the group consisting of halogen, —OH, —CN, —NO2, ═O, —OC(O)R1, —OR1, —C(O)R1, —C(O)NR1R2, —OC(O)NR1R2, —NR2C(O)R1, —NR1C(O)NR2R3, —CO2R1, —NR1R2, —NR2CO2R1, —SW, —S(O)R1, —S(O)2R1, —S(O)2NR1R2, —NR1S(O)2R2, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heterocyclyl;
• substituted C6-10 aryl, substituted 5- to 10-membered heteroaryl, or substituted 3- to 10-membered heterocyclyl, may have from 1-4 substituents independently selected from the group consisting of halogen, unsubstituted C1-8 alkyl, unsubstituted C1-8 haloalkyl, unsubstituted 4- to 7-membered heterocycle, —CN, —NO2, —OR1, ═O, —OC(O)R1, —CO2R1, —C(O)R1, —C(O)NR1R2, —OC(O)NR1R2, —NR2C(O)R1, —NR1C(O)NR2R3, —NR1R2, —NR2CO2R1, —SR1, —S(O)R1, —S(O)2R1, —S(O)2NR1R2, and —NR1S(O)2R, with the proviso that if X represents a heterocycle, suitable substituents preferably do not include another heterocycle;
• R1, R2 and R3 are each independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, aryl-C1-4 alkyl, aryloxy-C1-4 alkyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, or where R1 and R2, or R3 and R2, or R1 and R3, may together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring;
• and where the aliphatic and aromatic portions of R1, R2 and R3 are optionally further substituted with from 1 to 3 substituents selected from the group consisting of halogen, —OH, —ORm, —OC(O)NHRm, —OC(O)NRmRn, —SH, —SRm, —S(O)Rm, —S(O)2Rm, —S(O)2NH2, —S(O)2NHRm, —S(O)2NRmRn, —NHS(O)2Rm, —NRmS(O)2Rn, —C(O)NH2, —C(O)NHRm, —C(O)N(Rm)2, —C(O)Rm, —NHC(O)Rm, —NRmC(O)Rn, —NHC(O)NH2, —NRmC(O)NH2, —NRmC(O)NHRn, —NHC(O)NHRm, —NRoC(O)NRmRn, —NHC(O)N(Rm)2, —CO2H, —CO2Rm, —NHCO2Rm, —NRmCO2Rn, —CN, —NO2, —NH2, —NHRn, —NRmRn, —NRmS(O)NH2 and —NRmS(O)2NHRn, where Rm, Rn, and Ro are each independently unsubstituted C1-6 alkyl;
• Y represents from 1 to 4 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, —OR4, —C(O)R4, —CO2R4, —SR4, —S(O)R4, —S(O)2R4, and unsubstituted or substituted C1-4 alkyl;
• substituted C1-4 alkyl may have from 1 to 3 substituents independently selected from the group consisting of halogen, —OR4, —CN, —NO2, ═O, —OC(O)R4, —CO2R4, —C(O)R4, —CONR4R5, —OC(O)NR4R5, NR4C(O)R5, —NR4C(O)NR5R6, —NR4R5, —NR4CO2R5, —SR4, —SOR4, —SO2R4, —SO2NR4R5, and —NR4SO2R5;
• R4, R5 and R6 are each independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C6-10 aryl, and 5- to 10-membered heteroaryl;
• or where R4 and R5, or R6 and R4 or R5 and R6, together with the atom to which they are attached, form a substituted or unsubstituted 5-, 6- or 7-membered ring;
• and the aliphatic and aromatic portions of R4, R5, and R6 are optionally further substituted with from 1 to 3 substituents selected from the group consisting of halogen, —OH, —ORm, —OC(O)NHRm, —OC(O)NRmRn, —SH, —SRm, —S(O)Rm, —S(O)2Rm, —S(O)2NH2, —S(O)2NHRm, —S(O)2NRmRn, —NHS(O)2Rm, —NRmS(O)2Rn, —C(O)NH2, —C(O)NHRm, —C(O)N(Rm)2, —C(O)Rm, —NHC(O)Rm, —NRmC(O)Rn, —NHC(O)NH2, —NRmC(O)NH2, —NRmC(O)NHRn, —NHC(O)NHRm, —NRoC(O)NRmRn, —NHC(O)N(Rm)2, —CO2H, —CO2Rm, —NHCO2Rm, —NRmCO2Rn, —CN, —NO2, —NH2, —NHRn, —NRmRn, —NRmS(O)NH2 and —NRmS(O)2NHRn, where Rm, Rn, and Ro are each independently unsubstituted C1-6 alkyl;
• and
• Z represents from 0 to 5 substituents independently selected from the group consisting of halogen, unsubstituted or substituted C1-8 alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C2-8 alkynyl, —CN, —NO2, —OR7, —OC(O)R7, —CO2R7, —C(O)R7, —CONR7R8, —OC(O)NR7R8, —NR7C(O)R8, —NR7C(O)NR8R9, —NR7R8, —NR7CO2R8, —SR7, —S(O)R7, —S(O)2R7, —SO2NR7R8, —NR7SO2R8, unsubstituted or substituted C6-10 aryl, unsubstituted or substituted 5- to 10-membered heteroaryl and unsubstituted or substituted 3- to 10-membered heterocyclyl;
• substituted C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl substituents on Z may have from 1 to 5 substituents independently selected from the group consisting of halogen, —OR7, —CN, —NO2, ═O, —CN, —NO2, —OC(O)R7, —CO2R7, —C(O)R7, —CONR7R8, —OC(O)NR7R8, —NR7C(O)R8, —NR7C(O)NR8R9, —NR7R8, —NR7CO2R8, —SR7, —S(O)R7, —S(O)2R7, SO2NR7R8, —NR7SO2R8, unsubstituted or substituted phenyl, unsubstituted or substituted 5- or 6-membered heteroaryl, or unsubstituted or substituted 4- to 7-membered heterocyclyl;
• substituted aryl, heteroaryl and heterocyclyl substituents on Z may have from 1 to 5 substituents independently selected from the group consisting of halogen, —OR7, —CN, —NO2, ═O, —OC(O)R7, —OC(O)R7, —CO2R7, —C(O)R7, —CONR7R8, —OC(O)NR7R8, —NR7C(O)R8, —NR7C(O)NR8R9, —NR7R8, —NR7CO2R8, —SR7, —SOR7, —SO2R7, —SO2NR7R8, —NR7SO2R8, unsubstituted 4- to 7-membered heterocyclyl, unsubstituted C1-8 alkyl and unsubstituted C1-8 haloalkyl;
• R7, R8 and R9 are each independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C6-10 aryl, 5 to 10 membered heteroaryl and 3- to 10-membered heterocycle, or R7 and R8, or R8 and R9, or R7 and R9, may together with the atom(s) to which they are attached, form a substituted or unsubstituted 5-, 6-, or 7-membered ring;
• and
• the aliphatic and aromatic portions of R7, R8 and R9 are optionally further substituted with 1 to 3 substituents selected from the group consisting of halogen, —OH, —ORm, —OC(O)NHRm, —OC(O)NRmRn, —SH, —SRm, —S(O)Rm, —S(O)2Rm, —S(O)2NH2, —S(O)2NHRm, —S(O)2NRmRn, —NHS(O)2Rm, —NRmS(O)2Rn, —C(O)NH2, —C(O)NHRm, —C(O)N(Rm)2, —C(O)Rm, —NHC(O)Rm, —NRmC(O)Rn, —NHC(O)NH2, —NRmC(O)NH2, —NRmC(O)NHRn, —NHC(O)NHRm, —NRoC(O)NRmRn, —NHC(O)N(Rm)2, —CO2H, —CO2Rm, —NHCO2Rm, —NRmCO2Rn, —CN, —NO2, —NH2, —NHRn, —NRmRn, —NRmS(O)NH2 and —NRmS(O)2NHRn, where Rm, Rn, and Ro are each independently unsubstituted C1-6 alkyl.