Design and microwave-assisted synthesis of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles: novel agents with analgesic and anti-inflammatory properties.
In this work, we reported the synthesis and evaluation of the analgesic and anti-inflammatory properties of novel 3- or 4-substituted 5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-1-carboxyamidepyrazoles (where 3-/4-substituent=H/H, Me/H, Et/H, Pr/H, i-Pr/H, Bu/H, t-Bu/H, Ph/H, 4-Br-Ph/H and H/Me) designed in the exploration of the bioisosteric replacement of benzene present in salicylamide with a 5-trifluoromethyl-4,5-dihydro-1H-pyrazole scaffold. Target compounds were synthesized from the cyclocondensation of 4-alkoxy-1,1,1-trifluoromethyl-3-alken-2-ones with semicarbazide hydrochloride through a rapid one-pot reaction via microwave irradiation. In addition to spectroscopic data, the structure of the compounds was supported by X-ray diffraction. Subcutaneous administration of the 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles decreased pain-related behavior during neurogenic and inflammatory phases of the formalin test in mice. Moreover, the more active analgesic compounds (3-/4-=Et/H and H/Me) significantly decreased carrageenan-induced paw edema in mice. The data obtained in this work suggest that the synthesized compounds could be promising candidates for the future development of novel analgesic and anti-inflammatory agents.
Sauzem
Patricia D
PD
Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil.
Machado
Pablo
P
Rubin
Maribel A
MA
da S Sant'anna
Gabriela
G
Faber
Henrique B
HB
de Souza
Alessandra H
AH
Mello
Carlos F
CF
Beck
Paulo
P
Burrow
Robert A
RA
Bonacorso
Helio G
HG
Zanatta
Nilo
N
Martins
Marcos A P
MA
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008872:Microwaves; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011720:Pyrazoles