Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. matthew_morrissette@merck.com
Modification of lead compound 1 by reducing lipophilicity in the P3 group produced a series of low molecular weight thrombin inhibitors with excellent potency in functional assays, metabolic stability, and oral bioavailability. These modifications led to the identification of two optimized compounds, 14 and 16.