Development of tryptase inhibitors derived from thalidomide.
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.
Tetsuhashi
Masashi
M
Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Ishikawa
Minoru
M
Hashimoto
Mariko
M
Hashimoto
Yuichi
Y
Aoyama
Hiroshi
H
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D010797:Phthalimides / Q000737:chemistry; D013792:Thalidomide / Q000737:chemistry* / Q000494:pharmacology*; D053802:Tryptases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D010797:Phthalimides; D013792:Thalidomide; C037430:N-phenylphthalimide; D053802:Tryptases