(3 R)-3-Amino-4-(2,4,5-trifluorophenyl)- N-{4-[6-(2-methoxyethoxy)benzothiazol-2-yl]tetrahydropyran-4-yl}butanamide as a potent dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

Novel series of 3-amino- N-(4-aryl-1,1-dioxothian-4-yl)butanamides and 3-amino- N-(4-aryltetrahydropyran-4-yl)butanamides were synthesized and evaluated as dipeptidyl peptidase IV (DPP-IV) inhibitors. Derivatives incorporating the 6-substituted benzothiazole group showed highly potent DPP-IV inhibitory activity. Oral administration of (3 R)-3-amino-4-(2,4,5-trifluorophenyl)- N-{4-[6-(2-methoxyethoxy)benzothiazol-2-yl]tetrahydropyran-4-yl}butanamide ( 12u) reduced blood glucose excursion in an oral glucose tolerance test.