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

R Shimazawa; H Takayama; F Kato; M Kato; Y Hashimoto

doi:10.1016/s0960-894x(99)00034-7

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

Bioorg Med Chem Lett. 1999 Feb 22;9(4):559-62. doi: 10.1016/s0960-894x(99)00034-7.

Authors

R Shimazawa¹, H Takayama, F Kato, M Kato, Y Hashimoto

Affiliation

¹ Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.

PMID: 10098663
DOI: 10.1016/s0960-894x(99)00034-7

Abstract

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Dipeptidyl Peptidase 4 / drug effects*
Humans
Phthalimides / chemistry*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*

Substances

Phthalimides
Protease Inhibitors
N-phenylphthalimide
Dipeptidyl Peptidase 4