학술논문
Design and synthesis of conformationally restricted eight-Membered ring diketones as potential serine protease inhibitors
Document Type
Article
Author
Source
Subject
*KETONES
*AMIDES
*SERINE proteinases
*PLASMIN
*
*
*
Language
ISSN
0960-894X
Abstract
The design of conformationally restricted eight-membered ring diketones as transition state mimics of the mechanism of action of cyclotheonamides on serine proteases is described. Two target compounds are prepared from mutilin, derived from the natural product pleuromutilin. Compound 3 shows significant inhibition of plasmin and urokinase in enzyme rate assays, but an analogue 4 in which the amide moiety has been omitted does not. An X-ray crystal structure of the diketone 3 confirms the conformational predictions made by molecular modelling. [Copyright &y& Elsevier]