title: Design, synthesis, and thrombin-inhibitory activity of pyridin-2-ones as P2/P3 core motifs.
abstract: Guided by available X-ray crystal structure data on the serine protease thrombin, a series of pyridin-2-one derivatives were designed and synthesized having diverse functionality at the P(1) and P(3) sites. Potent in vitro activity against thrombin, with excellent selectivity over trypsin was found for selected analogues.
authors.affiliation: Department of Chemistry, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Que., Canada H3C 3J7. stephen.hanessian@umontreal.ca
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
authors.forename: Daniel
authors.initials: D
authors.lastname: Simard
authors.forename: Malken
authors.initials: M
authors.lastname: Bayrakdarian
authors.forename: Eric
authors.initials: E
authors.lastname: Therrien
authors.forename: Ingemar
authors.initials: I
authors.lastname: Nilsson
authors.forename: Ola
authors.initials: O
authors.lastname: Fjellström
mesh_terms: D000588:Amines / Q000737:chemistry; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000588:Amines; D011728:Pyridones; D013449:Sulfonamides; C017679:2-hydroxypyridine; D014357:Trypsin; D013917:Thrombin