1-[4-(1H-Benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea derivatives as small molecule heparanase inhibitors.
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.
Pan
Weitao
W
Department of Chemistry, ImClone Systems Incorporated, 710 Parkside Avenue, Brooklyn, NY 11226, USA.
Miao
Hua-Quan
HQ
Xu
Yong-Jiang
YJ
Navarro
Elizabeth C
EC
Tonra
James R
JR
Corcoran
Erik
E
Lahiji
Armin
A
Kussie
Paul
P
Kiselyov
Alexander S
AS
Wong
Wai C
WC
Liu
Hu
H
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
D002224:Carbanilides; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D000099175:Heparanase