An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology.
Deshpande MS, Wei J, Luo G, Cianci C, Danetz S, Torri A, Tiley L, Krystal M, Yu KL, Huang S, Gao Q, Meanwell NA.
Structure-activity studies associated with the salicylic acid-derived inhibitor of influenza fusion, BMY-27709, were examined using a parallel synthesis approach. This SAR survey led to the discovery of potent influenza inhibitory activity in a series of aromatic amides and thioamides derived from 1,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH-induced fusion process, thereby blocking viral entry into host cells. In a plaque-reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14 microg/mL.