title: Synthesis and evaluation of acylguanidine FXa inhibitors.
abstract: A series of acylguanidine derivatives were prepared and investigated as inhibitors of Factor Xa (FXa). These compounds were made by guanidine acylation with carboxylic acids using carbonyl diimidazole (CDI) as the coupling reagent. Conditions for the rapid synthesis and purification of these compounds are described along with their ability to inhibit FXa. The best FXa inhibitor is 1 with a FXa IC(50) of 6 nM.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08543-5400, USA. steve.oconnor@bms.com
authors.forename: Stephen P
authors.initials: SP
authors.lastname: O'Connor
authors.forename: Karnail
authors.initials: K
authors.lastname: Atwal
authors.forename: Chi
authors.initials: C
authors.lastname: Li
authors.forename: Eddie C-K
authors.initials: EC
authors.lastname: Liu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Seiler
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Shi
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Philip D
authors.initials: PD
authors.lastname: Stein
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis / Q000494:pharmacology; D000990:Antithrombin III / Q000138:chemical synthesis* / Q000494:pharmacology*; D001777:Blood Coagulation; D002264:Carboxylic Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D015951:Factor Xa / Q000737:chemistry*; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006147:Guanine / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure
chemical_list: D000925:Anticoagulants; D002264:Carboxylic Acids; D006146:Guanidines; D007093:Imidazoles; D006147:Guanine; D000990:Antithrombin III; D015951:Factor Xa