An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology

Structure-activity studies associated with the salicylic acid-derived inhib itor of influenza fusion, BMY-27709, were examined using a parallel synthes is approach. This SAR survey led to the discovery of potent influenza inhib itory activity in a series of aromatic amides and thioamides derived from 1 ,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were charac terized as inhibitors of the HI subtype of influenza A viruses that act by preventing the pl-l-induced fusion process, thereby blocking viral entry in to host cells. In a plaque-reduction assay, the most potent inhibitors disp layed EC50 values of 0.02-0.14 mug/mL. (C) 2001 Elsevier Science Ltd. All r ights reserved.