α-glucosidase inhibitors with a 4,5,6,7-tetrachlorophthalimide skeleton pendanted with a cycloalkyl or dicarba-closo-dodecaborane group

Abstract

Previous studies of α-glucosidase inhibitors derived from thalidomide revealed that 4,5,6,7-tetrachloro-N-alkylphthalimide derivatives are superior lead compounds. Structure - activity relationship studies indicated that a hydrophobic group at the N(2) position is mandatory for potent activity. Accordingly, we have designed and synthesized some 4,5,6,7-tetrachloro-N-cycloalkylphthalimide and 4,5,6,7-tetrachloro-N-dicarba-closo-dodecaborane derivatives. The prepared compounds exhibited potent α-glucosidase-inhibitory activity. Among them, 4,5,6,7-tetrachloro-N-cycloheptylphthalimide (9) showed the most potent activity, being approximately 30 times more active than the classical inhibitor, 1-deoxynojirimycin (1).