Quadruple Functionalized Pyrazole Pharmacophores by One‐pot Regioselective [3+2] Cycloaddition of Fluorinated Nitrile Imines and Dicyanoalkenes
Yin Zhou, Cheng‐Feng Gao, Hai Ma, Jing Nie, Jun‐An Ma, Fa‐Guang Zhang
Abstract
-aryl 3-di/trifluoro-methyl-4/5-cyanopyrazole pharmacophores from readily available hydrazonyl chlorides and dicyanoalkenes. The realization of this [3+2] cycloaddition reaction hinges upon the employment of N-aryl di/trifluoromethyl nitrile imines as the 1,3-dipoles to bypass external synthetic steps and dicyanoalkenes as the dipolarophiles to tune the regioselectivity. This one-pot strategy offers access to a divergent library of cyano analogues of prevalent 3-di/trifluoromethyl pyrazole pharmacophores, among which several compounds have shown potent inhibitory activity towards cyclooxygenase 2 (COX-2) compared with marketed drug Celecoxib.
Topics & Concepts
RegioselectivityNitrilePharmacophorePyrazoleCycloadditionChemistryCombinatorial chemistryOrganic chemistryStereochemistryCatalysisFluorine in Organic ChemistrySynthesis and Biological EvaluationSynthesis and Reactions of Organic Compounds