α-glucosidase inhibitors with a phthalimide skeleton:: Structure-activity relationship study

alpha-Glucosidase inhibitors with a phthalimide skeleton were prepared. Structure-activity relationship studies indicated a critical role for the hydrophobicity of the substituent at the nitrogen atom of the phthalimide skeleton. Introduction of electron-withdrawing groups, including a nitro group and chlorine, influenced the activity. Optimization studies led us to design 4,5,6,7-tetrachluro-N-phenylphthalimide (CPOP) and its N-phenylalkyl derivatives. CPOP and 4.5,6,7-tetrachloro-N-(4-phenylbutyl)phthalimide (CP4P) proved to be more potent alpha-glucosidase inhibitors than the known inhibitor 1-deoxynojirimycin.