title: 1-[4-(1H-Benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea derivatives as small molecule heparanase inhibitors.
abstract: A novel class of 1-[4-(1H-benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-ureas are described as potent inhibitors of heparanase. Among them are 1,3-bis-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea (7a) and 1,3-bis-[4-(5,6-dimethyl-1H-benzoimidazol-2-yl)-phenyl]-urea (7d), which displayed good heparanase inhibitory activity (IC(50) 0.075-0.27 microM). Compound 7a showed good efficacy in a B16 metastasis model.
authors.affiliation: Department of Chemistry, ImClone Systems Incorporated, 710 Parkside Avenue, Brooklyn, NY 11226, USA.
authors.forename: Weitao
authors.initials: W
authors.lastname: Pan
authors.forename: Hua-Quan
authors.initials: HQ
authors.lastname: Miao
authors.forename: Yong-Jiang
authors.initials: YJ
authors.lastname: Xu
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Navarro
authors.forename: James R
authors.initials: JR
authors.lastname: Tonra
authors.forename: Erik
authors.initials: E
authors.lastname: Corcoran
authors.forename: Armin
authors.initials: A
authors.lastname: Lahiji
authors.forename: Paul
authors.initials: P
authors.lastname: Kussie
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kiselyov
authors.forename: Wai C
authors.initials: WC
authors.lastname: Wong
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D002224:Carbanilides / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D009362:Neoplasm Metastasis / Q000188:drug therapy; D013329:Structure-Activity Relationship; D000099175:Heparanase
chemical_list: D002224:Carbanilides; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D000099175:Heparanase