title: Non-covalent thrombin inhibitors featuring P(3)-heterocycles with P(1)-monocyclic arginine surrogates.
abstract: Investigations on P(2)-P(3)-heterocyclic dipeptide surrogates directed towards identification of an orally bioavailable thrombin inhibitor led us to pursue novel classes of achiral, non-covalent P(1)-arginine derivatives. The design, synthesis, and biological activity of inhibitors NC1-NC30 that feature three classes of monocyclic P(1)-arginine surrogates will be disclosed: (1) (hetero)aromatic amidines, amines and hydroxyamidines, (2) 2-aminopyrazines, and (3) 2-aminopyrimidines and 2-aminotetrahydropyrimidines.
authors.affiliation: Department of Medicinal Chemistry, Corvas International, Inc., 3030 Science Park Road, San Diego, CA 92121, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Reiner
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Siev
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Araldi
authors.forename: Jingrong Jean
authors.initials: JJ
authors.lastname: Cui
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Ho
authors.forename: Komandla Malla
authors.initials: KM
authors.lastname: Reddy
authors.forename: Lala
authors.initials: L
authors.lastname: Mamedova
authors.forename: Phong H
authors.initials: PH
authors.lastname: Vu
authors.forename: Kuen Shan S
authors.initials: KS
authors.lastname: Lee
authors.forename: Nathaniel K
authors.initials: NK
authors.lastname: Minami
authors.forename: Tony S
authors.initials: TS
authors.lastname: Gibson
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Anderson
authors.forename: Annette E
authors.initials: AE
authors.lastname: Bradbury
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Nolan
authors.forename: J Edward
authors.initials: JE
authors.lastname: Semple
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001120:Arginine / Q000737:chemistry*; D004285:Dogs; D006571:Heterocyclic Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000991:Antithrombins; D006571:Heterocyclic Compounds; D001120:Arginine