Treating diabetes with dipeptidyl peptidase-IV inhibitors

摘要

The present invention is directed to novel substituted dihydropyrrolopyrazoles of structural Formula I which are inhibitors of the dipeptidyl peptidase-N enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase IV enzyme is involved.;

主权项

1. A compound of structural Formula I:or a pharmaceutically acceptable salt thereof; wherein
R1, R2 and R4 are independently selected from the group consisting of C1-6alkyl, halogen and hydrogen; R3 is hydrogen or halogen or, taken together with R5, form a C5-7 cycloalkyl or 5-7 membered heterocycle wherein the cycloalkyl or heterocycle is unsubstituted or substituted with 1-3 substituents selected from the group consisting of —OH, C1-6alkyl, halogen and C1-6 alkoxy; R5 is hydrogen, halogen, heterocycle, C3-7 cycloalkyl or, taken together with the carbon R5 is attached, form a C3-7 cycloalkyl or 4-7 membered heterocycle wherein the cycloalkyl or heterocycle is unsubstituted or substituted with 1-3 substituents selected from the group consisting of —OH, C1-6 alkyl, halogen and C1-6 alkoxy or, taken together with R3, form a C5-7 cycloalkyl or 5-7 membered heterocycle wherein the cycloalkyl or heterocycle is unsubstituted or substituted with 1-3 substituents selected from the group consisting of —OH, C1-6alkyl, halogen and C1-6alkoxy or, taken together with R6, form an aryl, cyclopropyl C5-7cycloalkyl or 5-7 membered heterocycle wherein the aryl, cycloalkyl or heterocycle is unsubstituted or substituted with 1-3 substituents selected from the group consisting of —OH, C1-6 alkyl, halogen and C1-6alkoxy; R6 is hydrogen, heterocycle, C3-7 cycloalkyl or, together with the carbon R6 is attached, form a C3-7 cycloalkyl or 4-7 membered heterocycle wherein the cycloalkyl or heterocycle is unsubstituted or substituted with 1-3 substituents selected from the group consisting of —OH, C1-6alkyl, halogen and C1-6alkoxy or taken together with R5 form an aryl, cyclopropyl C5-7cycloalkyl or 5-7 membered heterocycle wherein the aryl, cycloalkyl or heterocycle is unsubstituted or substituted with 1-3 substituents selected from the group consisting of —OH, C1-6alkyl, halogen and C1-6alkoxy; R7 is selected from the group consisting of hydrogen C1-6alkyl, C1-6alkylOH and C1-6alkoxy; wherein R5, R6, and R7 cannot be simultaneously hydrogen; and R8 is selected from the group consisting of hydrogen, C1-6 alkyl, SO2C1-6 alkyl, and SO2C3-6 cycloalkyl.