An efficient synthetic methodology to provide indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives is described. These conformationally restricted heterobicyclic scaffolds were evaluated as a novel class of HCV inhibitors. Introduction of an acyl group at the NH2 of the thiourea moiety has been found to enhance inhibitory activity. The chain length and the position of the alkyl group on the indoline aromatic ring markedly influenced anti-HCV activity. The indoline scaffold was more potent than the corresponding indole and tetrahydroquinoline scaffolds and analogue 31 displayed excellent activity (EC50 = 510 nM) against HCV without significant cytotoxicity (CC50 >50 μM).
Date:
2009-08-01
Relation:
Bioorganic and Medicinal Chemistry Letters. 2009 Aug 1;19(15):4134-4138.
