A pyrazolyl-thiazole derivative causes antinociception in mice

Abstract

The present study investigates the antinociceptive effect of the pyrazolyl-thiazole derivative 2-(5-trichloromethyl-5-hydroxy-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)-5-methylthiazole (B50) in mice. Male albino Swiss mice (30-40 g) were used in the acetic acid-induced abdominal writhes and tail-immersion tests. B50 caused dose-dependent antinociception (8, 23 and 80 µmol/kg, sc) in the acetic acid writhing assay (number of writhes: vehicle: 27.69 ± 6.15; B50 (8 µmol/kg): 16.92 ± 3.84; B50 (23 µmol/kg): 13.85 ± 3.84; B50 (80 µmol/kg): 9.54 ± 3.08; data are reported as means ± SEM for 9 animals per group). On the other hand, B50 did not cause antinociception in the tail immersion assay. Naloxone (2.75 µmol/kg, sc) prevented B50-induced antinociception (number of writhes: vehicle-saline: 31.11 ± 3.15; vehicle-naloxone: 27.41 ± 3.70; B50 (80 µmol/kg)-saline: 8.70 ± 3.33; B50 (80 µmol/kg)-naloxone: 31.84 ± 4.26; morphine-saline: 2.04 ± 3.52; morphine-naloxone: 21.11 ± 4.26; 8-9 animals per group). The removal of the methyl group of the thiazole ring of B50 or substitution of the bromo substituent with the methyl at position 4 of the phenyl group, which is attached to the thiazole ring of B50, resulted in loss of activity, suggesting that these substituents are important for antinociceptive activity. B50 had no effect on spontaneous locomotion or rotarod performance, indicating that the antinociceptive effect of B50 is not related to nonspecific motor effects. The antinociceptive profile of B50 seems to be closer to nonsteroidal anti-inflammatory drugs than to classic opioid agents, since it had no analgesic effect in a thermally motivated test. Key wordsThe pyrazole ring is a heterocycle compound containing two contiguous nitrogen atoms and three carbon atoms. Until 1995, in a few cases, only 5-trifluoromethyl-5-hydroxy-1H-pyrazolines and pyrazolidines could be synthesized, and pyrazolines other than 5-trifluoromethylated ones had been detected only by special nuclear magnetic resonance techniques (1). In 1999, Bonacorso et al. (2) described for the first time the synthesis and structural elucidation by nuclear magnetic resonance, Austin Model 1 calculations and X-ray diffraction of a novel series of twelve 3-aryl(alkyl)-5-hydroxy-1-

Antinociceptive action of 4-methyl-5-trifluoromethyl-5-hydroxy-4, 5-dihydro-1H-pyrazole methyl ester in models of inflammatory pain in mice

“…MPF4 is a novel pyrazole derivative discovered by screening compounds containing a pyrazole scaffold to find new antinociceptive drugs (De Souza et al, 2001;Godoy et al, 2004;Tabarelli et al, 2004;Prokopp et al, 2006;Sauzem et al, 2008). Recently, it was reported that MPF4 presented antinociceptive effects in formalin and hot-plate tests with efficacies similar to dipyrone or morphine (Milano et al, 2008).…”

Crystal structure of (E)-2-(5-(4-fluorophenyl)-3-(furan-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)-5-((4-fluorophenyl)diazenyl)-4-methylthiazole, C23H17F2N5OS

“…Many pyrazolylthiazoles have been synthesized using different procedures and showed antinociceptive, anti-inflammatory and antimicrobial activities [2][3][4][5][6][7][8][9][10]. The X-ray crystal structures for related compounds have been published recently [11,12].…”

An Efficient One‐pot Synthesis of Aryl‐substituted 1‐(Thiazol‐2‐yl)‐1H‐pyrazole‐3‐carboxylates via a Hantzsch Synthesis‐Knorr Reaction Sequence

“…7,159.7,152.4,146.0,145.6,133.6,129.8 (2C),129.4,129.2,128.6 (2C),128.3,128.0 (2C),125.9 (2C),111.7,111.4,61.5,14.4;HRMS (ESI) (d,J＝7.2 Hz,2H),7.49 (d,J＝8.4 Hz,2H),7.43 (d,J＝8.4 Hz,2H),4H),6.99 (s,1H),4.47 (q,J＝7.2 Hz,2H), 1.44 (t, J＝7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ: 161. 3, 128.0, 125.8 (2C), 121.6, 110.4, 61.3, 14.4, 9.4 2,159.6,152.2,143.6,138.5,136.3,136.1,133.6,132.9,129.4,128.7 (2C),128.2,128.1,127.1,125.7 (2C),122.5,110.0,61.3,14.4,9.2;HRMS (ESI) 3,159.8,152.2,…”