Low molecular weight thrombin inhibitors with excellent potency, metabolic stability, and oral bioavailability.
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.
Morrissette
Matthew M
MM
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. matthew_morrissette@merck.com
Stauffer
Kenneth J
KJ
Williams
Peter D
PD
Lyle
Terry A
TA
Vacca
Joseph P
JP
Krueger
Julie A
JA
Lewis
S Dale
SD
Lucas
Bobby J
BJ
Wong
Bradley K
BK
White
Rebecca B
RB
Miller-Stein
Cynthia
C
Lyle
Elizabeth A
EA
Wallace
Audrey A
AA
Leonard
Yvonne M
YM
Welsh
Denise C
DC
Lynch
Joseph J
JJ
McMasters
Daniel R
DR
D000284:Administration, Oral; D000991:Antithrombins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D004355:Drug Stability; D008970:Molecular Weight
D000991:Antithrombins