title: Optimization of the beta-aminoester class of factor Xa inhibitors. Part 1: P(4) and side-chain modifications for improved in vitro potency.
abstract: A systematic modification of the C(3) side-chain of the beta-aminoester class of factor Xa inhibitors and a survey of P(4) variations is described. These changes have resulted in the identification of sub-nanomolar inhibitors with improved selectivity versus related proteases. Coagulation parameters (i.e., APTT doubling concentrations) are also improved.
authors.affiliation: Drug Innovation and Approval, Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ 08807, USA. mark.czekaj@aventis.com
authors.forename: Mark
authors.initials: M
authors.lastname: Czekaj
authors.forename: Scott I
authors.initials: SI
authors.lastname: Klein
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Guertin
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Gardner
authors.forename: Allison L
authors.initials: AL
authors.lastname: Zulli
authors.forename: Henry W
authors.initials: HW
authors.lastname: Pauls
authors.forename: Alfred P
authors.initials: AP
authors.lastname: Spada
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Cheney
authors.forename: Karen D
authors.initials: KD
authors.lastname: Brown
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Colussi
authors.forename: Valeria
authors.initials: V
authors.lastname: Chu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Leadley
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Dunwiddie
mesh_terms: D004952:Esters; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004952:Esters; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors