Synthesis and structure-activity relationship studies of new 3-methyl-5-(5-propyl-1H-1-R'-3-pyrazolyl)-1H-1-R-4-nitrosopyrazoles as antimicotic agents

We have reported that some 4-nitrosopyrazoles derivatives displayed in vitro and in vivo potent antifungal activity at no cytotoxic concentration and some of these compounds were 4 times more potent than Amphotericine B and Fluconazole respectively against Cryptococcus.Neoformans and C. Krusei.We reported also that the absence of NO group or its replacement with NO2 or NH2 groups gave compounds devoid of antimycotical activity. To better understand the mechanism of action and with the aim of identifying the chemical features responsible for the action, we synthesized and tested a new class of compounds in which the 4-NO group was replaced with 4-CN group having, these last, similar steric and electronic features, but different routes by which may be metabolized in vivo.