title: N-(4-{[4-(1H-Benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamide derivatives as small molecule heparanase inhibitors.
abstract: A novel class of N-(4-{[4-(1H-benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamides are described as inhibitors of the endo-beta-glucuronidase heparanase. Among them are N-(4-{[4-(1H-benzoimidazol-2-yl)-phenylamino]-methyl}-phenyl)-3-bromo-4-methoxy-benzamide (15h), and N-(4-{[5-(1H-benzoimidazol-2-yl)-pyridin-2-ylamino]-methyl}- phenyl)-3-bromo-4-methoxy-benzamide (23) which displayed good heparanase inhibitory activity (IC(50) 0.23-0.29 microM), with the latter showing oral exposure in mice.
authors.affiliation: Department of Chemistry, ImClone Systems Incorporated, 710 Parkside Avenue, Brooklyn, NY 11226, USA.
authors.forename: Yong-Jiang
authors.initials: YJ
authors.lastname: Xu
authors.forename: Hua-Quan
authors.initials: HQ
authors.lastname: Miao
authors.forename: Weitao
authors.initials: W
authors.lastname: Pan
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Navarro
authors.forename: James R
authors.initials: JR
authors.lastname: Tonra
authors.forename: Stan
authors.initials: S
authors.lastname: Mitelman
authors.forename: M Margarita
authors.initials: MM
authors.lastname: Camara
authors.forename: Dhanvanthri S
authors.initials: DS
authors.lastname: Deevi
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kiselyov
authors.forename: Paul
authors.initials: P
authors.lastname: Kussie
authors.forename: Wai C
authors.initials: WC
authors.lastname: Wong
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D015394:Molecular Structure; D008970:Molecular Weight; D013329:Structure-Activity Relationship; D000099175:Heparanase
chemical_list: D001549:Benzamides; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D000099175:Heparanase