Author/Authors :
Daniel J. Sall، نويسنده , , Stephen L. Briggs، نويسنده , , Nickolay Y. Chirgadze، نويسنده , , David K. Clawson، نويسنده , , Donetta S. Gifford-Moore، نويسنده , , Valentine J. Klimkowski، نويسنده , , Jefferson R. McCowan، نويسنده , , Gerald F. Smith، نويسنده , , James H. Wikel، نويسنده ,
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.
