RESUMO
Three (S)-prolinol-derived conformationally restricted analogues of the antitubercular agent ethambutol were prepared and tested against Mycobacterium tuberculosis.
Assuntos
Antituberculosos/síntese química , Antituberculosos/farmacologia , Etambutol/síntese química , Etambutol/farmacologia , Antituberculosos/química , Desenho de Fármacos , Etambutol/análogos & derivados , Etambutol/química , Iminas/química , Modelos Moleculares , Conformação Molecular , Mycobacterium tuberculosis/efeitos dos fármacosRESUMO
The stereoselective preparation of novel C-alkyl 5-membered ring imino sugars and their biological evaluation with regard to GCS inhibition and cytotoxicity in a murine melanoma model are reported.
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Glucosiltransferases/antagonistas & inibidores , Imino Açúcares/química , Imino Açúcares/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
We developed a stereocontrolled route allowing potential access to the eight isomers of 4-benzylaminohex-5-ene-1,2,3-triol in two or four steps and ca. 50% yield from readily available chiral nonracemic cis- or trans-alpha,beta-epoxyimine precursors. A new (NH(4))(2)CO(3)-based carboxylation/intramolecular cyclization sequence allowed regio- and stereocontrolled C-3 epoxide opening while neat C-2 hydrolysis was ensured by simple aqueous acidic treatment.