title: Neutral inhibitors of the serine protease factor Xa.
abstract: A neutral inhibitor of the serine protease factor Xa was identified via a high-throughput screen of a commercial library. The initial lead 1 demonstrated reversible and competitive inhibition kinetics for factor Xa and possessed a high degree of selectivity versus other related serine proteases. Initial modeling efforts and the generation of a series of analogues of 1 are described.
authors.affiliation: Departments of Medicinal Chemistry, Structural Chemistry and Enzymology, Axys Pharmaceuticals, Inc., 180 Kimball Way, 94080, South San Francisco, CA, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Shrader
authors.forename: W B
authors.initials: WB
authors.lastname: Young
authors.forename: P A
authors.initials: PA
authors.lastname: Sprengeler
authors.forename: J C
authors.initials: JC
authors.lastname: Sangalang
authors.forename: K
authors.initials: K
authors.lastname: Elrod
authors.forename: G
authors.initials: G
authors.lastname: Carr
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000990:Antithrombin III / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D020134:Catalytic Domain / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D005341:Fibrinolysin / Q000187:drug effects; D006801:Humans; D008403:Mass Screening; D008958:Models, Molecular; D009010:Monte Carlo Method; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013917:Thrombin / Q000187:drug effects*; D014357:Trypsin / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects*
chemical_list: D000814:Aniline Compounds; D013876:Thiophenes; D000990:Antithrombin III; D014357:Trypsin; D013917:Thrombin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator