title: Design and microwave-assisted synthesis of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles: novel agents with analgesic and anti-inflammatory properties.
abstract: 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.
authors: 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.
authors: Patricia D
authors: PD
authors: Sauzem
authors: Pablo
authors: P
authors: Machado
authors: Maribel A
authors: MA
authors: Rubin
authors: Gabriela
authors: G
authors: da S Sant'anna
authors: Henrique B
authors: HB
authors: Faber
authors: Alessandra H
authors: AH
authors: de Souza
authors: Carlos F
authors: CF
authors: Mello
authors: Paulo
authors: P
authors: Beck
authors: Robert A
authors: RA
authors: Burrow
authors: Helio G
authors: HG
authors: Bonacorso
authors: Nilo
authors: N
authors: Zanatta
authors: Marcos A P
authors: MA
authors: Martins
mesh_terms: 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
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011720:Pyrazoles