Synthesis and anti-tubercular activity of novel alkyl substituted riminophenazine derivatives / 药学学报
Acta Pharmaceutica Sinica
;
(12): 745-754, 2012.
Artigo
em Inglês
| WPRIM
| ID: wpr-276249
ABSTRACT
A series of novel riminophenazine derivatives bearing an alkyl substituent attached to N-5 and imino nitrogen at C-3 position of the phenazine ring were obtained through rational drug design, aiming to maintain high anti-tubercular activity, lower toxicity and reduce lipophilicity. All target compounds were prepared by utilizing simple and flexible synthetic route and evaluated against Mycobacterium tuberculosis H37Rv and screened for mammalian cytotoxicity. The results demonstrated that compounds with a cyclopropyl substituent at N-5 position were more active than the reference compound clofazimine. In particular, 2-(4-chloroanilino)-5-cyclopropyl-3-(4-methoxycyclohexyl) imino-3, 5-dihydrophenazine (25) was found to be the most potent compound with low cytotoxicity and lipophilicity. This compound could serve as a valuable lead molecule for further optimization.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Fenazinas
/
Células Vero
/
Desenho de Fármacos
/
Estrutura Molecular
/
Testes de Sensibilidade Microbiana
/
Chlorocebus aethiops
/
Química
/
Mycobacterium tuberculosis
/
Antituberculosos
Limite:
Animais
Idioma:
Inglês
Revista:
Acta Pharmaceutica Sinica
Ano de publicação:
2012
Tipo de documento:
Artigo
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