title: C6 modification of the pyridinone core of thrombin inhibitor L-374,087 as a means of enhancing its oral absorption.
abstract: 1 (L-374,087) is a potent, selective, efficacious, and orally bioavailable thrombin inhibitor that contains a core 3-amino-2-pyridinone moiety. Replacement of the C6 pyridinone methyl group of 1 by a propyl group gave 5 (L-375,052), which retained all the excellent properties of 1, and also yielded higher plasma levels after oral dosing in dogs and rats.
authors.affiliation: Department of Biological Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Isaacs
authors.forename: K J
authors.initials: KJ
authors.lastname: Cutrona
authors.forename: C L
authors.initials: CL
authors.lastname: Newton
authors.forename: P E
authors.initials: PE
authors.lastname: Sanderson
authors.forename: M G
authors.initials: MG
authors.lastname: Solinsky
authors.forename: E P
authors.initials: EP
authors.lastname: Baskin
authors.forename: I W
authors.initials: IW
authors.lastname: Chen
authors.forename: C M
authors.initials: CM
authors.lastname: Cooper
authors.forename: J J
authors.initials: JJ
authors.lastname: Cook
authors.forename: S J
authors.initials: SJ
authors.lastname: Gardell
authors.forename: S D
authors.initials: SD
authors.lastname: Lewis
authors.forename: R J
authors.initials: RJ
authors.lastname: Lucas
authors.forename: E A
authors.initials: EA
authors.lastname: Lyle
authors.forename: J J
authors.initials: JJ
authors.lastname: Lynch
authors.forename: A M
authors.initials: AM
authors.lastname: Naylor-Olsen
authors.forename: M T
authors.initials: MT
authors.lastname: Stranieri
authors.forename: K
authors.initials: K
authors.lastname: Vastag
authors.forename: J P
authors.initials: JP
authors.lastname: Vacca
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011728:Pyridones / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D013424:Sulfanilamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000991:Antithrombins; C116624:L 374087; C116663:L 375052; D011725:Pyridines; D011728:Pyridones; D013424:Sulfanilamides; D013449:Sulfonamides