Low molecular weight thrombin inhibitors with excellent potency, metabolic stability, and oral bioavailability.
Morrissette MM,
Stauffer KJ,
Williams PD,
Lyle TA,
Vacca JP,
Krueger JA,
Lewis SD,
Lucas BJ,
Wong BK,
White RB,
Miller-Stein C,
Lyle EA,
Wallace AA,
Leonard YM,
Welsh DC,
Lynch JJ,
McMasters DR.
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.
PMID: 15261262 [PubMed - indexed for MEDLINE]