Benzylmaltosides as inhibitors of smooth muscle cell proliferation

A method of treating or inhibiting hyperproliferative vascular disorders in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of formula I having the structure

• Y is hydrogen, halogen, azido, or Het optionally substituted with R10;
• Het is 1,3-dioxo-1,3-dihydro-isoindol-2-yl, imidazol-1-yl, or benzimidazol-1-yl;
• R1, R2, R3 and R4, are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, benzoyl, or benzyl;
• R5 is hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, nitrile, nitro, alkoxy of 1-6 carbon atoms;
• R6 and R7, are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, perfluoroalkylsulfonyl of 1-6 carbon atoms, arylsulfonyl of 6-10 carbon atoms, or arylsulfonyl substituted with halo of 6-10 carbon atoms;
• R8 and R9, are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitriloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, aryl of 6-10 carbon atoms, aryl of 6-10 carbon atoms substituted with R11, aralkyl of 7-12 carbon atoms or aralkyl of 7-12 carbon atoms substituted with R11;
• R10 is halogen, nitrile, nitro, amino, acylamino of 2-7 carbon atoms, perfluoroacylamino of 2-7 carbon atoms, carboxyl, carboxyaldehyde, perfluoroalkyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, perfluoroalkoxy of 1-6 carbon atoms, alkoxycarbonyl of 2-7 carbon atoms, perfluoroalkoxycarbonyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, or mercapto;
• R11 is halogen, nitrile, nitro, or perfluoroalkyl of 1-6 carbon atoms;
• or a pharmaceutically acceptable salt thereof.

A method of treating or inhibiting restenosis in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of formula I having the structure

• Y is hydrogen, halogen, azido, or Het optionally substituted with R10;
• Het is 1,3-dioxo-1,3-dihydro-isoindol-2-yl, imidazol-1-yl, or benzimidazol-1-yl;
• R1, R2, R3 and R4, are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, benzoyl, or benzyl;
• R5 is hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, nitrile, nitro, alkoxy of 1-6 carbon atoms;
• R6 and R7, are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, perfluoroalkylsulfonyl of 1-6 carbon atoms, arylsulfonyl of 6-10 carbon atoms, or arylsulfonyl substituted with halo of 6-10 carbon atoms;
• R8 and R9, are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitriloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, aryl of 6-10 carbon atoms, aryl of 6-10 carbon atoms substituted with R11, aralkyl of 7-12 carbon atoms or aralkyl of 7-12 carbon atoms substituted with R11;
• R10 is halogen, nitrile, nitro, amino, acylamino of 2-7 carbon atoms, perfluoroacylamino of 2-7 carbon atoms, carboxyl, carboxyaldehyde, perfluoroalkyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, perfluoroalkoxy of 1-6 carbon atoms, alkoxycarbonyl of 2-7 carbon atoms, perfluoroalkoxycarbonyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, or mercapto;
• R11 is halogen, nitrile, nitro, or perfluoroalkyl of 1-6 carbon atoms;
• or a pharmaceutically acceptable salt thereof.

A method of inhibiting angiogenesis in a malignant tumor, sarcoma, or neoplastic tissue in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of formula I having the structure

• Y is hydrogen, halogen, azido, or Het optionally substituted with R10;
• Het is 1,3-dioxo-1,3-dihydro-isoindol-2-yl, imidazol-1-yl, or benzimidazol-1-yl;
• R1, R2, R3 and R4, are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, benzoyl, or benzyl;
• R5 is hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, nitrile, nitro, alkoxy of 1-6 carbon atoms;
• R6 and R7, are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, perfluoroalkylsulfonyl of 1-6 carbon atoms, arylsulfonyl of 6-10 carbon atoms, or arylsulfonyl substituted with halo of 6-10 carbon atoms;
• R8 and R9, are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitriloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, aryl of 6-10 carbon atoms, aryl of 6-10 carbon atoms substituted with R11, aralkyl of 7-12 carbon atoms or aralkyl of 7-12 carbon atoms substituted with R11;
• R10 is halogen, nitrile, nitro, amino, acylamino of 2-7 carbon atoms, perfluoroacylamino of 2-7 carbon atoms, carboxyl, carboxyaldehyde, perfluoroalkyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, perfluoroalkoxy of 1-6 carbon atoms, alkoxycarbonyl of 2-7 carbon atoms, perfluoroalkoxycarbonyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, or mercapto;
• R11 is halogen, nitrile, nitro, or perfluoroalkyl of 1-6 carbon atoms;
• or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition which comprises a compound of formula I having the structure

• Y is hydrogen, halogen, azido, or Het optionally substituted with R10;
• Het is 1,3-dioxo-1,3-dihydro-isoindol-2-yl, imidazol-1-yl, or benzimidazol-1-yl;
• R1, R2, R3 and R4, are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, benzoyl, or benzyl;
• R5 is hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, nitrile, nitro, alkoxy of 1-6 carbon atoms;
• R6 and R7, are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, perfluoroalkylsulfonyl of 1-6 carbon atoms, arylsulfonyl of 6-10 carbon atoms, or arylsulfonyl substituted with halo of 6-10 carbon atoms;
• R8 and R9, are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitriloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, aryl of 6-10 carbon atoms, aryl of 6-10 carbon atoms substituted with R11, aralkyl of 7-12 carbon atoms or aralkyl of 7-12 carbon atoms substituted with R11;
• R10 is halogen, nitrile, nitro, amino, acylamino of 2-7 carbon atoms, perfluoroacylamino of 2-7 carbon atoms, carboxyl, carboxyaldehyde, perfluoroalkyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, perfluoroalkoxy of 1-6 carbon atoms, alkoxycarbonyl of 2-7 carbon atoms, perfluoroalkoxycarbonyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, or mercapto;
• R11 is halogen, nitrile, nitro, or perfluoroalkyl of 1-6 carbon atoms;
• or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.