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New 2‐Oxoimidazolidine Derivatives: Design,Synthesis and Evaluation of Anti‐BK Virus Activities in Vitro
Authors:Yurii Kornii  Svitlana Chumachenko  Oleg Shablykin  Mark N Prichard  Scott H James  Caroll Hartline  Victor Zhirnov  Volodymyr Brovarets
Abstract:A series of novel 2‐oxoimidazolidine derivatives were synthesized and their antiviral activities against BK human polyomavirus type 1 (BKPyV) were evaluated in vitro. Bioassays showed that the synthesized compounds 1‐{(4E)‐5‐(dichloromethylidene)‐2‐oxoimidazolidin‐4‐ylidene]sulfamoyl}piperidine‐4‐carboxylic acid ( 5 ) and N‐Cyclobutyl‐N′‐(4E)‐5‐(dichloromethylidene)‐2‐oxoimidazolidin‐4‐ylidene]sulfuric diamide ( 4 ) exhibited moderate activities against BKPyV (EC50=5.4 and 5.5 μm , respectively) that are comparable to the standard drug Cidofovir. Compound 5 exhibited the same cytotoxicity in HFF cells and selectivity index (SI50) as Cidofovir. The selectivity index of compound 4 is three times less than that of Cidofovir due to the higher toxicity of this compound. Hence, these compounds may be taken as lead compound for further development of novel ant‐BKPyV agents.
Keywords:2-oxoimidazolidine derivatives  BK polyomavirus  antiviral activity  cytotoxicity
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