AUTHOR=Desideri Nicoletta , Fioravanti Rossella , Proietti Monaco Luca , Atzori Elena Maria , Carta Antonio , Delogu Ilenia , Collu Gabriella , Loddo Roberta 

TITLE=Design, Synthesis, Antiviral Evaluation, and SAR Studies of New 1-(Phenylsulfonyl)-1H-Pyrazol−4-yl-Methylaniline Derivatives

JOURNAL=Frontiers in Chemistry

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2019.00214

DOI=10.3389/fchem.2019.00214

ISSN=2296-2646

ABSTRACT=<p>A series of <italic>N</italic>-((3-phenyl-1-(phenylsulfonyl)-1<italic>H</italic>-pyrazol-4-yl)methyl)anilines <bold>7a-p</bold> and <bold>8a-l</bold>, structurally related to previously synthesized and tested (<italic>N</italic>-(1,3-diphenyl-1<italic>H</italic>-pyrazol-4-yl)methyl)anilines (<bold>1a-v</bold>), were designed and synthesized. The new derivatives were evaluated in cell-based assays for their cytotoxicity and antiviral activity against a large panel of RNA and DNA viruses of public health significance. Generally, the tested compounds did not display cytotoxicity toward the cell lines used. The majority of derivatives <bold>7a</bold>-<bold>p</bold> were able to interfered with YFV and RSV replication in the micromolar range showing a marked improvement in potency and selectivity with respect to the reference inhibitors 6-azauridine and ribavirin, respectively. The introduction of a <italic>p</italic>-methoxy substituent on the phenylsulfonyl group (compounds <bold>8a-l</bold>) completely abolished the anti-RSV activity and reduced or eliminated the potency against YFV. On the contrary, several <italic>p</italic>-methoxy analogs were able to interfere with BVDV replication with a comparable (<bold>8b, 8c, 8g</bold>, and <bold>8k</bold>) or better (<bold>8a</bold> and <bold>8f</bold>) potency than the reference inhibitor, ribavirin. Compound <bold>7e</bold>, selected for time of addition experiments on BHK-21 cell cultures infected with YFV, achieved the highest reduction of virus titer when added 2 h post infection and maintained up to 4 h post infection.</p>