Quadruple Functionalized Pyrazole Pharmacophores by One‐pot Regioselective [3+2] Cycloaddition of Fluorinated Nitrile Imines and Dicyanoalkenes. Issue 15 (9th June 2022)

• Record Type: Journal Article
• Authors: Zhou, Yin; Gao, Cheng‐Feng; Ma, Hai; Nie, Jing; Ma, Jun‐An; Zhang, Fa‐Guang
• Is Part Of: Chemistry, an Asian journal. Volume 17:Issue 15(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-09
• Subjects: pyrazoles -- pharmacophores -- di/trifluoromethyl group -- cycloaddition -- COX-2 inhibitors; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/asia.202200436
• Languages: English
• ISSNs: 1861-4728

Abstract

Abstract: Here we present a quadruple functionalization approach for the modular construction of fully substituted N 1 ‐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. Abstract : Quadruple Functionalization : A one‐pot regioselective [3+2] cycloaddition platform of fluorinated nitrile imines with dicyanoalkenes was established to produce a broad variety of fully substituted N 1 ‐aryl 3‐di/trifluoromethyl‐4/5‐cyanopyrazole pharmacophores.