RESUMEN
Three (S)-prolinol-derived conformationally restricted analogues of the antitubercular agent ethambutol were prepared and tested against Mycobacterium tuberculosis.
Asunto(s)
Antituberculosos/síntesis química , Antituberculosos/farmacología , Etambutol/síntesis química , Etambutol/farmacología , Antituberculosos/química , Diseño de Fármacos , Etambutol/análogos & derivados , Etambutol/química , Iminas/química , Modelos Moleculares , Conformación Molecular , Mycobacterium tuberculosis/efectos de los fármacosRESUMEN
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.
Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Glucosiltransferasas/antagonistas & inhibidores , Iminoazúcares/química , Iminoazúcares/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Estructura Molecular , Relación Estructura-ActividadRESUMEN
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.