Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 2. Exploring
D J Sall1, S L Briggs, N Y Chirgadze
1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Abstract:
In an effort to increase the thrombin inhibitory activity of a novel series of inhibitors (i.e., 1a), substituents were incorporated at the C-3" position of the C-3 aryl ring (2). Consistent with the X-ray crystallography studies, small hydrophobic groups at the C-3" site (Br and Me) enhanced thrombin inhibitory activity by 8-fold. However, a few more hydrophilic substituents (NO2 and OMe) also enhanced the potency of the series. The biological results are discussed in terms of molecular modeling studies.
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