N-(2-(hetaryl)aryl)arylsulfonamides and N-(2-(hetaryl)hetaryl)arylsulfonamides

摘要

Compounds are provided that act as potent antagonists of the CCR9 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists.

主权项

1. A compound, salt, or N-oxide of the formula (I): where Ar1 is a substituted or unsubstituted C6-10 aryl or substituted or unsubstituted 5- to 10-membered heteroaryl; each having 0 to 5 substituents 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, ═O, —C(O)R3, —CO2R3, —C(O)NR3R4, —OR3, —OC(O)R3, —OC(O)NR3R4, —NR5C(O)R3, —NR5C(O)NR3R4, —NR3R4, —NR5CO2R3, —NR5S(O)2R3, —SR3, —S(O)R3, —S(O)2R3, —S(O)2NR3R4, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; A is N; X1X2X3 are selected from the group consisting of: N—N═N N—C(R6)═N N—N═C(R7) N—C(R6)═C(R7) C═N—C(R7) C═C(R6)—N(R5) R1 is hydrogen or C1-8 alkyl; each R2, R3, R4, R6 and R7, when present, are independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, —CN, ═O, —NO2, —OR′, —OC(O)R′, —CO2R′, —C(O)R′, —C(O)NR″R′, —OC(O)NR″R′, —NR′″C(O)R′, —NR′″C(O)NR″R′, —NR″R′, —NR′″CO2R′, —SR′, —S(O)R′, —S(O)2R′, —S(O)2NR″R′, —NR″S(O)2R′, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl; or R2 and R3 together with the atoms which they substitute form a substituted or unsubstituted 5-, 6-, or 7-membered ring; each R5 is independently selected from group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, —CO2R′, —C(O)R′, —C(O)NR″R′, —S(O)R′, —S(O)2R′, —S(O)2NR″R′, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; and R′, R″ and R′″ are each independently hydrogen or unsubstituted C1-4 alkyl; or R′ and R″ together with the atoms which they substitute form a substituted or unsubstituted 5-, 6-, or 7-membered ring.