Design and synthesis of indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives as novel HCV inhibitors

Abstract An efficient synthetic methodology to provide indole, 2,3-dihydro-indole, and 3,4-dihydro-2 H -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 NH 2 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 (EC 50  = 510 nM) against HCV without significant cytotoxicity (CC 50 >50 μM).