title: Synthesis and antinociceptive activity of new 2-substituted 4-(trifluoromethyl)-5,6-dihydrobenzo[h]quinazolines.
abstract: A useful synthetic route for an initial new series of 2-substituted 4-(trifluoromethyl)-5,6-dihydrobenzo[h]quinazolines (3), as well as an evaluation of their analgesic effect in a mice pain model, is reported. Five new quinazolines were formed from the cyclocondensation reactions of 2,2,2-trifluoro-1-(1-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)ethanone (1) with some well-known amidine salts [NH2CR(=NH)] (2), in which R=H, Me, Ph, NH2 and SMe, at a 40-70% yield. Subsequently, due to the importance of the pyrrole nucleus, a 2-(pyrrol-1-yl)quinazoline (4) was obtained through a Clauson-Kaas reaction from the respective 2-(amino)quinazoline, in a reaction with 2,5-dimethoxy-tetrahydrofuran. The analgesic evaluation demonstrated that four 5,6-dihydrobenzo[h]quinazolines (compounds of 3c (R=Ph), 3d (R=NH2), 3e (R=SMe), and 4 (R=pyrrol-1-yl); 100mg/kg, p.o.) and ketoprofen (100mg/kg, p.o.) significantly reduced the spontaneous nociception in a capsaicin-induced test. Moreover, in comparison with ketoprofen (100 and 300mg/kg, p.o.), compound 3c (30-300mg/kg, p.o.) showed an anti-hyperalgesic action in an arthritic pain model without locomotor alterations in the mice, suggesting that quinazoline 3c is a promising prototype scaffold for new analgesic drugs in the treatment of pathological pain such as that in arthritis.
authors: Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil. Electronic address: helio.bonacorso@ufsm.br.
authors: Helio G
authors: HG
authors: Bonacorso
authors: Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Wilian C
authors: WC
authors: Rosa
authors: Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Sara M
authors: SM
authors: Oliveira
authors: Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Indiara
authors: I
authors: Brusco
authors: Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Camila C Dalla
authors: CCD
authors: Pozza
authors: Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Pablo A
authors: PA
authors: Nogara
authors: Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Carson W
authors: CW
authors: Wiethan
authors: Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Melissa B
authors: MB
authors: Rodrigues
authors: Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Clarissa P
authors: CP
authors: Frizzo
authors: Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.
authors: Nilo
authors: N
authors: Zanatta
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D051379:Mice; D062105:Molecular Docking Simulation; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D011799:Quinazolines
keywords: Anti-hyperalgesic effect; Arthritis; Pyrroles; Quinazolines; Trifluoromethyl