title: Design and synthesis of glycolic and mandelic acid derivatives as factor Xa inhibitors.
abstract: A series of glycolic and mandelic acid derivatives was synthesized and investigated for their factor Xa inhibitory activity. These analogues are highly potent and selective inhibitors against fXa. In a rabbit deep vein thrombosis model, compound 26 showed significant antithrombotic effects (81% inhibition of thrombus formation) at 1.1 microM plasma concentration following intravenous administration.
authors.affiliation: COR Therapeutics, Inc., 256 East Grand Avenue, South San Francisco, CA 94080, USA. tsu@corr.com
authors.forename: T
authors.initials: T
authors.lastname: Su
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: B
authors.initials: B
authors.lastname: Doughan
authors.forename: K
authors.initials: K
authors.lastname: Kane-Maguire
authors.forename: C K
authors.initials: CK
authors.lastname: Marlowe
authors.forename: J P
authors.initials: JP
authors.lastname: Kanter
authors.forename: J
authors.initials: J
authors.lastname: Woolfrey
authors.forename: B
authors.initials: B
authors.lastname: Huang
authors.forename: P
authors.initials: P
authors.lastname: Wong
authors.forename: U
authors.initials: U
authors.lastname: Sinha
authors.forename: G
authors.initials: G
authors.lastname: Park
authors.forename: J
authors.initials: J
authors.lastname: Malinowski
authors.forename: S
authors.initials: S
authors.lastname: Hollenbach
authors.forename: R M
authors.initials: RM
authors.lastname: Scarborough
authors.forename: B Y
authors.initials: BY
authors.lastname: Zhu
mesh_terms: D000083:Acetanilides; D000578:Amidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D001780:Blood Coagulation Tests; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D065427:Factor Xa Inhibitors; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D008333:Mandelic Acids / Q000737:chemistry*; D010648:Phenylacetates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020246:Venous Thrombosis / Q000188:drug therapy
chemical_list: D000083:Acetanilides; D000578:Amidines; D065427:Factor Xa Inhibitors; D008333:Mandelic Acids; D010648:Phenylacetates; D015842:Serine Proteinase Inhibitors; C442369:alpha-(3-amidinylphenoxy)-2-bromo-N-(5-(pyrrolidin-1-ylcarbonyl)phenyl)phenylacetamide; D005341:Fibrinolysin; C037938:mandelic acid