RESUMO
A protecting-group-free synthetic approach to 1-phenylisoquinolin-4-ols was developed by the intramolecular thermal cyclization of methyl 2-[(diphenylmethylidene)amino]acetates. R1 and R2 substituents were found to affect the required reaction temperatures, time, and yields of the cyclized products. The reactivity of the Schiff bases increased upon introduction of α-benzoyl and α-ester groups (R2). The cyclization yield also depended on the position of the R1 substituents on the phenyl groups.
RESUMO
Four new pentacyclic benzodiazepine derivatives (PBDTs 13-16) were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.
Assuntos
Ansiolíticos/síntese química , Anticonvulsivantes/síntese química , Benzodiazepinonas/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Hipnóticos e Sedativos/síntese química , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Benzodiazepinonas/farmacologia , Benzodiazepinonas/uso terapêutico , Comportamento Exploratório/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Pentobarbital/toxicidade , Picrotoxina/toxicidade , Reflexo Anormal/efeitos dos fármacos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Estricnina/toxicidadeRESUMO
A series of amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives was synthesized from isatoic anhydride, and their cytotoxicity against the MRC-5 and Mahlavu cell lines was evaluated. The results suggest that compound PBDT-7i with the meta-trifluoromethylbenzoyl substituent can selectively inhibit the growth of Mahlavu cells and has low toxicity towards MRC-5 cells.