Synthesis and kinetic activity analysis of substituted pyrazole, pyrazoline, and pyrazolidine alcohol dehydrogenase inhibitors

Alcohol dehydrogenase inhibitors may be employed for the treatment of parasitic infection in humans. A series of substituted pyrazoline derivatives were synthesized to elucidate the pharmacophore for the inhibition of ADH. Targeted structure modification was used to alter the electronic and steric interactions associated with the enzyme active site. This study identified several effective N-aryl-carboxamide derivatives with horse liver ADH inhibition, comparable to that of 4-methylpyrazole, a known ADH inhibitor. The identification of pharmacophoric regions will allow for the methodological modification of these compounds to improve enzyme affinity and targeted inhibition. Future research may include additional solubility, toxicity and docking analysis of these compounds