5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia

Abstract

An efficient method to obtain six 4-alkoxy-2-oxo-but-3-enoic acid ethyl esters [EtO2CC(O)C(R2)=C(R1)OR, where R1/R2/R = Me/H/Me (2a), Ph/H/Me (2b), 4-MeC6H4/H/Me (2c), 4-BrC6H4/H/Me (2d), 4-FC6H4/H/Me (2e), H/Me/Et (2f)] from acylation of enol ethers or acetals with ethyl oxalyl chloride is reported. The cyclocondensation reaction of these substrates and their trifluormethylated analogues (5a-f) [CF3C(O)C(R2)=C(OR)R1] with salicylic hydrazide furnished a series of ethyl 5-hydroxy-1-(2-hydroxybenzoyl)-4,5-dihydro-1H-pyrazole-5-carboxylates (6) and 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-(2-hydroxybenzoyl)pyrazoles (7), respectively. The structure of the obtained compounds was determined by spectroscopy and confirmed by crystallographic studies. The design of these compounds explore the hypothesis that the hybridization of salicylic acid with an appropriate 4,5-dihydro-1Hpyrazole scaffold can supply novel potent analgesic agents. The oral administration of one compound of each series of pyrazoles (6a, 7a) caused significant analgesia in the writhing test in mice, which was similar to the analgesia caused by aspirin.