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Updated: Sep 22, 2025

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
Published on: June 10, 2021
Quadruple Functionalized Pyrazole Pharmacophores by One-pot Regioselective [3+2] Cycloaddition of Fluorinated Nitrile
Yin Zhou1, Cheng-Feng Gao1, Hai Ma2
1Department of Chemistry, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Frontiers Science Center for Synthetic Biology (Ministry of Education), and Tianjin Collaborative Innovation Centre of Chemical Science & Engineering, Tianjin University, 300072, Tianjin, P. R. China.
Abstract:
Here we present a quadruple functionalization approach for the modular construction of fully substituted N1 -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.
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