New synthetic thrombin inhibitors: molecular design and experimental verification.

ABSTRACT:

Background

The development of new anticoagulants is an important goal for the improvement of thromboses treatments.

Objectives

The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration.

Methods

Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field. This program takes into account the effects of solvent. The designed molecules with the best scoring functions (calculated binding energies) were synthesized and their thrombin inhibitory activity evaluated experimentally in vitro using a chromogenic substrate i

SUBMITTER: Sinauridze EI 

PROVIDER: S-EPMC3095642 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature