Development of tryptase inhibitors derived from thalidomide

Masashi Tetsuhashi; Minoru Ishikawa; Mariko Hashimoto; Yuichi Hashimoto; Hiroshi Aoyama

doi:10.1016/j.bmc.2010.05.037

Development of tryptase inhibitors derived from thalidomide

Bioorg Med Chem. 2010 Jul 15;18(14):5323-38. doi: 10.1016/j.bmc.2010.05.037. Epub 2010 Jun 1.

Authors

Masashi Tetsuhashi¹, Minoru Ishikawa, Mariko Hashimoto, Yuichi Hashimoto, Hiroshi Aoyama

Affiliation

¹ Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

PMID: 20561792
DOI: 10.1016/j.bmc.2010.05.037

Abstract

A novel series of tryptase inhibitors with a N-phenylphthalimide skeleton structurally derived from thalidomide (1) has been developed. Structure-activity relationship studies led to a potent and selective tryptase inhibitor, 2-(4-cyanophenyl)isoindole-1,3-dione-5-yl 3-(2-aminopyridin-5-yl)propanoate (7), with the IC50 value of 78 nM.

Publication types

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

MeSH terms

Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Humans
Models, Molecular
Phthalimides / chemistry
Thalidomide / chemistry*
Thalidomide / pharmacology*
Tryptases / antagonists & inhibitors*
Tryptases / metabolism*

Substances

Enzyme Inhibitors
Phthalimides
Thalidomide
N-phenylphthalimide
Tryptases