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J Med Chem ; 47(13): 3455-61, 2004 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-15189042

RESUMO

Tuberculosis is one of the most common infectious diseases known to man. About 37% of the world's population (about 1.86 billion people) are infected with Mycobacterium tuberculosis. According to the World Health Organization, every year approximately 8 million people develop active tuberculosis and almost 2 million of those die from the disease. The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing. The present drug regimen for treating tuberculosis has been in existence for 30 years. New drugs that will shorten total treatment duration, improve the treatment of MDR-TB, and address latent tuberculosis are the most urgent need of tuberculosis control programs. A new series of synthetic 3-amino-4-arylpyridazino[4,3-b]indoles (pyridazinoindoles) were identified as inhibitors of Mycobacterium tuberculosis. The design, synthesis, and antimycobacterial activity of these compounds are described. While the most active compounds are still not comparable to the front-line drugs rifampicin and isoniazid, they do show promise. Most of the pyridazinoindoles with appreciable antituberculosis activity also inhibit monoamine oxidase, suggestive of a novel inhibitory effect on mycobacterial redox reactions.


Assuntos
Antituberculosos/síntese química , Indóis/síntese química , Inibidores da Monoaminoxidase/síntese química , Mycobacterium tuberculosis/efeitos dos fármacos , Piridazinas/síntese química , Animais , Antituberculosos/química , Antituberculosos/farmacologia , Indóis/química , Indóis/farmacologia , Mitocôndrias Hepáticas/enzimologia , Monoaminoxidase/química , Monoaminoxidase/isolamento & purificação , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Piridazinas/química , Piridazinas/farmacologia , Ratos
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