Antimalarial Activity of Tri- and Tetra-Substituted Anilino Pyrazoles

Abstract

Pyrazole core represents a privilege scaffold in medicinal chemistry; a number of pyrazole compounds are endowed with various pharmacological activities in different therapeutic areas including antimalarial treatment. Supported by this evidence, a series of 5-anilino-3-(hetero)arylpyrazoles were evaluated for their antiplasmodial activity in in vitro assays. The compounds were synthesized according to regioselective and versatile protocols that combine active methylene reagents, aryl isothiocyanates and (substituted)hydrazines. The considered derivatives <b>2</b> allowed the definition of consistent structure-activity relationships and compounds <b>2b</b>,<b>e</b>,<b>k</b>,<b>l</b> were identified as the most interesting derivatives of the series showing micromolar IC₅₀ values against chloroquine-sensitive and chloroquine-resistant <i>Plasmodium</i> strains. Additionally, the most active anilino-pyrazoles did not show any cytotoxicity against tumor and normal cells and were predicted to have favorable drug-like and pharmacokinetic properties.