title: Structure-activity relationships of substituted benzothiophene-anthranilamide factor Xa inhibitors.
abstract: Compound 1 was identified by high throughput screening as a novel, potent, non-amidine factor Xa inhibitor with good selectivity against thrombin and trypsin. A series of modifications of the three aromatic groups of 1 was investigated. Substitution of chlorine or bromine for fluorine on the aniline ring led to the discovery of subnanomolar factor Xa inhibitors. Positions on the anthranilic acid ring that can accommodate further substitution were also identified.
authors.affiliation: Department of Medicinal Chemistry, Berlex Biosciences, PO Box 4099, Richmond, CA 94804-0099, USA. you-ling_chou@berlex.com
authors.forename: Yuo-Ling
authors.initials: YL
authors.lastname: Chou
authors.forename: David D
authors.initials: DD
authors.lastname: Davey
authors.forename: Keith A
authors.initials: KA
authors.lastname: Eagen
authors.forename: Brian D
authors.initials: BD
authors.lastname: Griedel
authors.forename: Rushad
authors.initials: R
authors.lastname: Karanjawala
authors.forename: Gary B
authors.initials: GB
authors.lastname: Phillips
authors.forename: Karna L
authors.initials: KL
authors.lastname: Sacchi
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Shaw
authors.forename: Shung C
authors.initials: SC
authors.lastname: Wu
authors.forename: Dao
authors.initials: D
authors.lastname: Lentz
authors.forename: Amy M
authors.initials: AM
authors.lastname: Liang
authors.forename: Lan
authors.initials: L
authors.lastname: Trinh
authors.forename: Michael M
authors.initials: MM
authors.lastname: Morrissey
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Kochanny
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis / Q000494:pharmacology; D002417:Cattle; D065427:Factor Xa Inhibitors; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D011517:Prothrombin Time; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D015842:Serine Proteinase Inhibitors; D013876:Thiophenes; D014361:Trypsin Inhibitors; D062367:ortho-Aminobenzoates; D013917:Thrombin