N-(4-{[4-(1H-Benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamide derivatives as small molecule heparanase inhibitors.
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.
Xu
Yong-Jiang
YJ
Department of Chemistry, ImClone Systems Incorporated, 710 Parkside Avenue, Brooklyn, NY 11226, USA.
Miao
Hua-Quan
HQ
Pan
Weitao
W
Navarro
Elizabeth C
EC
Tonra
James R
JR
Mitelman
Stan
S
Camara
M Margarita
MM
Deevi
Dhanvanthri S
DS
Kiselyov
Alexander S
AS
Kussie
Paul
P
Wong
Wai C
WC
Liu
Hu
H
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
D001549:Benzamides; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D000099175:Heparanase