title: The de novo design and synthesis of cyclic urea inhibitors of factor Xa: optimization of the S4 ligand.
abstract: In this report refinements to the S4 ligand group leads to compound 19, an inhibitor of fXa with good potency in vitro and an improved pharmacokinetic profile in rabbit. The X-ray crystallographic study of a representative analogue confirms our binding model for this series.
authors.affiliation: DuPont Pharmaceuticals Company, Wilmington, DE 19880-0500, USA. robert.a.galemmo@dupontpharma.com
authors.forename: R A
authors.initials: RA
authors.lastname: Galemmo
authors.forename: B L
authors.initials: BL
authors.lastname: Wells
authors.forename: K A
authors.initials: KA
authors.lastname: Rossi
authors.forename: R S
authors.initials: RS
authors.lastname: Alexander
authors.forename: C
authors.initials: C
authors.lastname: Dominguez
authors.forename: T P
authors.initials: TP
authors.lastname: Maduskuie
authors.forename: P F
authors.initials: PF
authors.lastname: Stouten
authors.forename: M R
authors.initials: MR
authors.lastname: Wright
authors.forename: B J
authors.initials: BJ
authors.lastname: Aungst
authors.forename: P C
authors.initials: PC
authors.lastname: Wong
authors.forename: R M
authors.initials: RM
authors.lastname: Knabb
authors.forename: R R
authors.initials: RR
authors.lastname: Wexler
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D065427:Factor Xa Inhibitors; D008024:Ligands; D008958:Models, Molecular; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D014508:Urea / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D065427:Factor Xa Inhibitors; D008024:Ligands; D015842:Serine Proteinase Inhibitors; D014508:Urea