N-(4-{[4-(1 H-Benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamide derivatives as small molecule heparanase inhibitors

The development of small molecule heparanase inhibitor 23 (IC 50 = 0.29 μM) is reported. A novel class of N-(4-{[4-(1 H-benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamides are described as inhibitors of the endo-β-glucuronidase heparanase. Among them are N-(4-{[4-(1 H-benzoimidazol-2-yl)-phenylamino]-methyl}-phenyl)-3-bromo-4-methoxy-benzamide ( 15h), and N-(4-{[5-(1 H-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 μM), with the latter showing oral exposure in mice.