title: Non-nucleoside inhibitors of the measles virus RNA-dependent RNA polymerase complex activity: Synthesis and in vitro evaluation.
abstract: High-throughput screening has identified 1-methyl-3-(trifluoromethyl)-N-[4-(pyrrolidinylsulfonyl)phenyl]-1H-pyrazole-5-carboxamide 16677 as a novel and potent (IC(50)=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 (CC(50)/IC(50)) of ca. 16,500.
authors.affiliation: Department of Chemistry, 1515 Dickey Drive, Emory University, Atlanta, GA 30322, USA. asun2@emory.edu
authors.forename: Aiming
authors.initials: A
authors.lastname: Sun
authors.forename: Nizal
authors.initials: N
authors.lastname: Chandrakumar
authors.forename: Jeong-Joong
authors.initials: JJ
authors.lastname: Yoon
authors.forename: Richard K
authors.initials: RK
authors.lastname: Plemper
authors.forename: James P
authors.initials: JP
authors.lastname: Snyder
mesh_terms: D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008459:Measles virus / Q000201:enzymology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D012324:RNA-Dependent RNA Polymerase