The design and synthesis of thrombin inhibitors: The introduction of in vivo efficacy and oral bioavailability into benzthiazolylalanine inhibitors

The further optimisation of the novel lead compound CGH752 (Fig. 1) is desc ribed. By introducing various substituents into the 6-position of the 3,3-d imethyltetrahydroquinoline (DMTHQS) ring we have been able to favourably af fect the in vitro and in vivo activity, and the pharmacokinetics of such co mpounds. One of the inhibitors synthesised (CGH1484) is bioavailable and sh ows efficacy in animal models of thrombosis. (C) 2000 Elsevier Science Ltd. All rights reserved.