Benzenesulfonamide compounds and their use as blockers of calcium channels

摘要

The invention relates to piperidinyl and hexahydroazepinyl compounds of Formula (I): and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein R1-R3, Z and q are defined as set forth in the specification. The invention is also directed to the use compounds of Formula (I) to treat, prevent or ameliorate a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.;

主权项

1. A compound having the Formula XI:or a pharmaceutically acceptable salt thereof, wherein:
R1 and R2 are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, halogen, alkoxy, haloalkoxy, cyano, nitro, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxy; q is 1; R3 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, hydroxyalkyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrofuranylalkyl, 3-tetrahydrofuranylalkyl, alkylsulfonylaminoalkyl, aminocarbonylalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cyanoalkyl, carboxyalkyl, and alkoxycarbonylalkyl; R8 and R9 are both hydrogen; p is 0, 1, 2, 3, or 4; D is —NH— or —N(alkyl)-, and R14 is selected from the group consisting of
phenyl optionally substituted with one or two substituents independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino;naphthyl optionally substituted with one or two substituents independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino;quinolinyl;pyridyl;phenyl substituted with phenyl, benzyl, phenoxy, or benzyloxy, wherein each phenyl ring is optionally substituted with one or two substituents independently selected from the group consisting of halogen, haloalkyl, alkyl, alkoxy, hydroxy, amino and cyano;alkyl optionally substituted with hydroxy; and—NR14aR14b, wherein R14a and R14b are each independently selected from the group consisting of
hydrogen; andalkyl; orR14a is hydrogen or alkyl, and R14b is selected from the group consisting ofaryl optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, alkoxycarbonyl, and haloalkoxy;benzyl optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, alkoxycarbonyl, and haloalkoxy;heteroaryl selected from pyridyl or benzothiazolyl optionally substituted with one of more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, alkoxycarbonyl, and haloalkoxy; andheteroarylalkyl selected from pyridylalkyl or benzothiazolylalkyl optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, alkoxycarbonyl, and haloalkoxy; or D is —C(O)—, —CH═CH—, or absent, and R14 is —NR14aR14b, wherein R14a and R14b are as defined above; provided that (i) when p is 0 and D is —NH—, then R14 is 3,5-trifluoromethylphenyl; or provided that (ii) R14a and R14b are not hydrogen at the same time.