title: Oxyguanidines. Part 2: Discovery of a novel orally active thrombin inhibitor through structure-based drug design and parallel synthesis.
abstract: Through structure-based drug design and parallel synthesis, we have discovered a novel series of nonpeptidic phenyl-based thrombin inhibitors using oxyguanidines as guanidine bioisosteres. These compounds have been found to be highly potent, highly selective, and orally bioavailable.
authors.affiliation: 3-Dimensional Pharmaceuticals, Inc., 665 Stockton Drive, Exton, PA 19341, USA. tlu3@prdus.jnj.com
authors.forename: Tianbao
authors.initials: T
authors.lastname: Lu
authors.forename: Thomas
authors.initials: T
authors.lastname: Markotan
authors.forename: Frank
authors.initials: F
authors.lastname: Coppo
authors.forename: Bruce
authors.initials: B
authors.lastname: Tomczuk
authors.forename: Carl
authors.initials: C
authors.lastname: Crysler
authors.forename: Stephen
authors.initials: S
authors.lastname: Eisennagel
authors.forename: John
authors.initials: J
authors.lastname: Spurlino
authors.forename: Lisa
authors.initials: L
authors.lastname: Gremminger
authors.forename: Richard M
authors.initials: RM
authors.lastname: Soll
authors.forename: Edward C
authors.initials: EC
authors.lastname: Giardino
authors.forename: Roger
authors.initials: R
authors.lastname: Bone
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D004285:Dogs; D015195:Drug Design; D006146:Guanidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006801:Humans; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D013917:Thrombin