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