Nonpeptide small-molecular inhibitors of dipeptidyl peptidase IV: N-phenylphthalimide analogs.
A novel series of nonpeptide small-molecular dipeptidyl peptidase IV (DPP-IV) inhibitors with an N-phenylphthalimide skeleton has been developed. Some of 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-diisopropylphenyl)phthalimide (12), and thiocarbonyl analogs of (2,6-diisopropylphenyl)phthalimide and their 4,5,6,7-tetrafluorinated derivative (18, 19 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-IV-specific inhibitor, while the others also showed inhibitory activity toward another peptidase, aminopeptidase N (APN).
Shimazawa
R
R
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Takayama
H
H
Kato
F
F
Kato
M
M
Hashimoto
Y
Y
D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects*; D006801:Humans; D010797:Phthalimides / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*
D010797:Phthalimides; D011480:Protease Inhibitors; C037430:N-phenylphthalimide; D018819:Dipeptidyl Peptidase 4