2-acylaminopropoanol-type glucosylceramide synthase inhibitors

A compound represented by the following structural formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is a phenyl group optionally substituted with one or more substituents selected from halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, —OR30, —SR30, —N(R31)2, Ar1, —Vo—OR30, —Vo—N(R31)2, —Vo—Ar1, —O—Vo—Ar1, —O—V1—N(R31)2, —S—Vo—Ar1, —S—V1—N(R31)2, —N(R31)—Vo—Ar1, —N(R31)—V1—N(R31)2, —O—[CH2]p—O—, —S—[CH2]p—S— or —[CH2]q—;
• Ar1 is a phenyl group each optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl or C1-C6 haloalkyl;
• and
• each R30 is independently
• i) hydrogen;
• ii) a phenyl group optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl or C1-C6 haloalkyl;
• or
• iii) an C1-C10 alkyl group optionally substituted with one or more substituents selected from halogen, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl or C1-C6 haloalkyl;
• and
• each R31 is independently R30, or —N(R31)2 is an optionally substituted non-aromatic heterocyclic group;
• —N(R2R3) is a pyrrolidinyl group optionally substituted with one or more substituents selected from halogen, alkyl, haloalkyl, —OR40, —O(haloalkyl), —SR40, —NO2, —CN, —N(R41)2, —NR41C(O)R40, —NR41C(O)OR42, —N(R41)C(O)N(R41)2, —C(O)R40, —C(S)R40, —C(O)OR40, —OC(O)R40, —C(O)N(R41)2, —S(O)2R40, —SO2N(R41)2, —S(O)R42, —SO3R40, Ar2, V2—Ar2, —V2—OR40, —V2—O(haloalkyl), —V2—SR40, —V2—NO2, —V2—CN, —V2—N(R41)2, —V2—NR41C(O)R40, —V2—NR41CO2R42, —V2—N(R41)C(O)N(R41)2, —V2—C(O)R40, —V2—C(S)R40, —V2—CO2R40, —V2—OC(O)R40, —V2—C(O)N(R41)2—, —V2—S(O)2R40, —V2—SO2N(R41)2, —V2—S(O)R42, —V2—SO3R40, —O—V2—Ar2 or —S—V2—Ar2;
• each V2 is independently a C1-C4 alkylene group;
• Ar2 is an aryl group each optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl or C1-C6 haloalkyl;
• and
• each R40 is independently
• i) hydrogen;
• ii) an aryl group optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl or C1-C6 haloalkyl;
• or
• iii) an C1-C10 alkyl group optionally substituted with one or more substituents selected from halogen, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl or C1-C6 haloalkyl;
• and
• each R41 is independently R40, —CO2R40, —SO2R40 or —C(O)R40;
• or
• —N(R41)2 taken together is an optionally substituted non-aromatic heterocyclic group;
• and each R42 is independently:
• i) an aryl group optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl or C1-C6 haloalkyl;
• or
• ii) an C1-C10 alkyl group optionally substituted with one or more substituents selected from halogen, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl or C1-C6 haloalkyl;
• R4 is an aliphatic group or an aryl group optionally substituted with one or more substituents selected from halogen, alkyl, haloalkyl, Ar3, Ar3—Ar3, —OR50, —O(haloalkyl), —SR50, —NO2, —CN, —NCS, —N(R51)2, —NR51C(O)R50, —NR51C(O)OR52, —N(R51)C(O)N(R51)2, —C(O)R50, —C(S)R50, —C(O)OR50, —OC(O)R50, —C(O)N(R51)2, —S(O)2R50, —SO2N(R51)2, —S(O)R52, —SO3R50, —NR51SO2N(R51)2, —NR51SO2R52, —V4—Ar3, —V—OR50, —V4—O(haloalkyl), —V4—SR50, —V4—NO2, —V4—CN, —V4—N(R51)2, —V4—NR51C(O)R50, —V4—NR51CO2R52, —V4—N(R51)C(O)N(R51)2, —V4—C(O)R50, —V4—C(S)R50, —V4—CO2R50, —V4—OC(O)R50, —V4—C(O)N(R51)2—, —V4—S(O)2R50, —V4—SO2N(R51)2, —V4—S(O)R52, —V4—SO3R50, —V4—NR51SO2N(R51)2, —V4—NR51SO2R52, —O—V4—Ar3, —O—V5—N(R51)2, —S—V4—Ar3, —S—V5—N(R51)2, —N(R51)—V4—Ar3, —N(R51)—V5—N(R51)2, —NR51C(O)—V4—N(R51)2, —NR51C(O)—V4—Ar3, —C(O)—V4—N(R51)2, —C(O)—V4—Ar3, —C(S)—V4—N(R51)2, —C(S)—V4—Ar3, —C(O)O—V5—N(R51)2, —C(O)O—V4—Ar3, —O—C(O)—V5—N(R51)2, —O—C(O)—V4—Ar3, —C(O)N(R51)—V5—N(R51)2, —C(O)N(R51)—V4—Ar3, —S(O)2—V4—N(R51)2, —S(O)2—V4—Ar3, —SO2N(R51)—V5—N(R51)2, —SO2N(R51)—V4—Ar3, —S(O)—V4—N(R51)2, —S(O)—V4—Ar3, —S(O)2—O—V5—N(R51)2, —S(O)2—O—V4—Ar3, —NR51SO2—V4—N(R51)2, —NR51SO2—V4—Ar3, —O—[CH2]p′—O—, —S—[CH2]p′—S—, or —[CH2]q′—;
• each V4 is independently a C1-C10 alkylene group;
• each V5 is independently a C2-C10 alkylene group;
• each Ar3 is independently an aryl group each optionally substituted with one or more substituents selected from halogen, alkyl, amino, alkylamino, dialkylamino, alkoxy, nitro, cyano, hydroxy, haloalkoxy or haloalkyl;
• and
• each R50 is independently
• i) hydrogen;
• ii) an aryl group optionally substituted with one or more substituents selected from halogen, alkyl, amino, alkylamino, dialkylamino, alkoxy, nitro, cyano, hydroxy, haloalkoxy, alkoxycarbonyl, alkylcarbonyl or haloalkyl;
• or
• iii) an alkyl group optionally substituted with one or more substituents selected from halogen, amino, alkylamino, dialkylamino, alkoxy, nitro, cyano, hydroxy, haloalkoxy, alkoxycarbonyl, alkylcarbonyl or haloalkyl;
• and
• each R51 is independently R50, —CO2R50, —SO2R50 or —C(O)R50;
• or
• —N(R51)2 taken together is an optionally substituted non-aromatic heterocyclic group;
• and each R52 is independently:
• i) an aryl group optionally substituted with one or two substituents selected from halogen, alkyl, amino, alkylamino, dialkylamino, alkoxy, nitro, cyano, hydroxy, haloalkoxy, alkoxycarbonyl, alkylcarbonyl or haloalkyl;
• or
• ii) an alkyl group optionally substituted with one or more substituents selected from halogen, amino, alkylamino, dialkylamino, alkoxy, nitro, cyano, hydroxy, haloalkoxy, alkoxycarbonyl, alkylcarbonyl or haloalkyl;
• and
• each p′ is 1, 2, 3 or 4;
• and
• each q′ is 3, 4, 5 or 6;
• and
• R7 is —H or C1-C6 alkyl.