Pyrazole‐Enaminones as Promising Prototypes for the Development of Analgesic Drugs.

This study reports the chemo‐ and regioselective synthesis, at good yields, of (E)‐4‐(amino)‐1,1,1‐trifluoro‐5‐(4,5‐alkyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐1‐yl)pent‐3‐en‐2‐ones (pyrazole‐enaminones), from the of N‐alkylation reaction of trifluoromethyl pyrazoles with 5‐bromo enaminones. The obtained compounds were tested as potential analgesics in a screening test involving mice. Three of these compounds significantly reduced the spontaneous nociception induced by the application of capsaicin, which is an algogenic substance. Compound 5 g presented satisfactory antinociceptive activity compared to celecoxib, a drug used as a positive control, without promoting locomotor changes in the mice. Moreover, molecular modeling simulations showed that compound 5 g interacts with the cyclooxygenase enzyme at the same binding site as celecoxib. Together, our data suggest that compound 5 g is a promising prototype for the development of new analgesic drugs. [ABSTRACT FROM AUTHOR]