Non-nucleoside inhibitors of the measles virus RNA-dependent RNA polymerase complex activity: Synthesis and in vitro evaluation

High-throughput screening has identified 1-methyl-3-(trifluoromethyl)-N-[4-(pyrrolidinylsulfonyl)phenyl]-1H-pyrazole-5-carboxamide 16677 as a novel and potent (IC50 = 35–145 nM) inhibitor against multiple primary isolates of diverse measles virus (MV) genotypes currently circulating worldwide. The synthesis of 16677 and several analogs together with effects on MV replication is described. The most potent analog displays nanomolar inhibition against the MV and a selectivity ratio (CC50/IC50) of ca. 16,500.

Graphical abstractHigh-throughput screening has identified a nanomolar inhibitor of measles virus. A series of analogs have been synthesized and the most active compound, 14d displayed low-nanomolar inhibition against the MV.Figure optionsDownload full-size imageDownload as PowerPoint slide