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

A series of -((3-phenyl-1-(phenylsulfonyl)-1-pyrazol-4-yl)methyl)anilines and , structurally related to previously synthesized and tested (-(1,3-diphenyl-1-pyrazol-4-yl)methyl)anilines (), 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 - 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 -methoxy substituent on the phenylsulfonyl group (compounds ) completely abolished the anti-RSV activity and reduced or eliminated the potency against YFV. On the contrary, several -methoxy analogs were able to interfere with BVDV replication with a comparable (, and ) or better ( and ) potency than the reference inhibitor, ribavirin. Compound , 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.