Nonpeptide small-molecular inhibitors of dipeptidyl peptidase IV: N-phenylphthalimide analogs

A novel series of nonpeptide small-molecular dipeptidyl peptidase IV (DPP-M inhibitors with an N-phenylphthalimide skeleton has been developed. Some o f the compounds, including 4-amino-(2,6-dimethylphenyl)phthalimides (7), 4- and 5-hydroxy-(2,6-diethylphenyl)phthalimide (11 and 14), 4-hydroxy-(2,6-d iisopropylphenyl)phthalimide (12), and thiocarbonyl analogs of (2,6-diisopr opylphenyl)phthalimide and their 4,5,6,7-tetrafluorinated derivative (18, 1 9 and 20), were more potent than the well-known DPP-IV-specific inhibitor, Pro-boroPro (PBP). Among them, 18 was revealed to be a DPP-TV-specific inhi bitor, while the others also showed inhibitory activity toward another pept idase, aminopeptidase N (APN). (C) 1999 Elsevier Science Ltd. All rights re served.