4-phenylsulfonamidopiperidines as calcium channel blockers

A compound having the Formula I:

• 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, and hydroxy;
• R3 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, hydroxyalkyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrofuranyl alkyl, 3-tetrahydrofuranylalkyl, alkylsulfonylaminoalkyl, and aminocarbonylalkyl;
• Z is selected from the group consisting of Z1, Z3, and Z4, wherein
• R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkylthiol, aminoalkyl and phenyl;
• or R4 and R5 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring wherein one or more carbon atoms of the heterocyclic ring are optionally replaced with NR16, O, or S, wherein R16 is hydrogen or C1-3 alkyl;
• R6 is hydrogen and R7 is selected from the group consisting of alkyl;
• hydroxyalkyl;
• alkoxyalkyl;
• haloalkyl;
• aminoalkyl;
• cycloalkyl;
• phenyl optionally substituted with one or two substituents independently selected from the group consisting of alkyl, cycloalkyl, halogen, cyano, amino, alkylamino, dialkylamino, hydroxy, nitro, haloalkyl, and alkoxy;
• benzyl optionally substituted with one or two substituents independently selected from the group consisting of alkyl, cycloalkyl, halogen, cyano, amino, alkylamino, dialkylamino, hydroxy, nitro, haloalkyl, and alkoxy;
• and
• benzyloxyalkyl;
• or
• R6 and R7 together with the carbon atom to which they are attached form a C3-7cycloalkyl group, or
• R7 is hydrogen, R4 is hydrogen or C1-3alkyl, and R5 and R6 together form a bridge —CH2—CH2—CH2— or —CH2—CHG1-CHG2-CH2—, wherein G1 and G2 are both hydrogen or together with the carbon atoms to which they are attached form a fused phenyl group;
• R8 and R9 are both hydrogen or together form ═O;
• R14 is selected from the group consisting of
• phenyl substituted with one or two substituents independently selected from the group consisting of 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;
• and
• 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;
• R15 is phenyl or naphthyl, either of which is optionally substituted with one or two substituents independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, amino, alkylamino and dialkylamino;
• D is C═O, —CH═CH—, or absent;
• m is 0 or 1;
• and
• o is 0, 1, 2, or 3;
• with the proviso that when Z is Z4, then R3 is cyclopropyl.