A series of N-((3-phenyl-1-(phenylsulfonyl)-1H-pyrazol-4-yl)methyl)anilines 7a-p and 8a-l, structurally related to previously synthesized and tested (N-(1,3-diphenyl-1H-pyrazol-4-yl)methyl)anilines (1a-v), 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 7a-p 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 p-methoxy substituent on the phenylsulfonyl group (compounds 8a-l) completely abolished the anti-RSV activity and reduced or eliminated the potency against YFV. On the contrary, several p-methoxy analogs were able to interfere with BVDV replication with a comparable (8b, 8c, 8g, and 8k) or better (8a and 8f) potency than the reference inhibitor, ribavirin. Compound 7e, 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.

design, synthesis, antiviral evaluation, and SAR studies of new 1-(phenylsulfonyl)-1H-pyrazol-4-yl-methylaniline derivatives / Desideri, Nicoletta; Fioravanti, Rossella; Proietti Monaco, Luca; Atzori, Elena Maria; Carta, Antonio; Delogu, Ilenia; Collu, Gabriella; Loddo, Roberta. - In: FRONTIERS IN CHEMISTRY. - ISSN 2296-2646. - 7:(2019). [10.3389/fchem.2019.00214]

design, synthesis, antiviral evaluation, and SAR studies of new 1-(phenylsulfonyl)-1H-pyrazol-4-yl-methylaniline derivatives

Desideri, Nicoletta
Primo
;
Fioravanti, Rossella
Secondo
;
Proietti Monaco, Luca;Atzori, Elena Maria;
2019

Abstract

A series of N-((3-phenyl-1-(phenylsulfonyl)-1H-pyrazol-4-yl)methyl)anilines 7a-p and 8a-l, structurally related to previously synthesized and tested (N-(1,3-diphenyl-1H-pyrazol-4-yl)methyl)anilines (1a-v), 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 7a-p 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 p-methoxy substituent on the phenylsulfonyl group (compounds 8a-l) completely abolished the anti-RSV activity and reduced or eliminated the potency against YFV. On the contrary, several p-methoxy analogs were able to interfere with BVDV replication with a comparable (8b, 8c, 8g, and 8k) or better (8a and 8f) potency than the reference inhibitor, ribavirin. Compound 7e, 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.
1-(phenylsulfonyl)-1H-pyrazole derivatives; BVDV; RSV; anti-Flavivirus activity; antiviral activity
01 Pubblicazione su rivista::01a Articolo in rivista
design, synthesis, antiviral evaluation, and SAR studies of new 1-(phenylsulfonyl)-1H-pyrazol-4-yl-methylaniline derivatives / Desideri, Nicoletta; Fioravanti, Rossella; Proietti Monaco, Luca; Atzori, Elena Maria; Carta, Antonio; Delogu, Ilenia; Collu, Gabriella; Loddo, Roberta. - In: FRONTIERS IN CHEMISTRY. - ISSN 2296-2646. - 7:(2019). [10.3389/fchem.2019.00214]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1275821
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