Alpha-glucosidase inhibitors with a 4,5,6,7-tetrachlorophthalimide skeleton pendanted with a cycloalkyl or dicarba-closo-dodecaborane group.
Previous studies of alpha-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 alpha-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).
Sou
S
S
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Takahashi
H
H
Yamasaki
R
R
Kagechika
H
H
Endo
Y
Y
Hashimoto
Y
Y
D001880:Boranes / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D010797:Phthalimides / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
D001880:Boranes; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D010797:Phthalimides