ABSTRACT
Three (S)-prolinol-derived conformationally restricted analogues of the antitubercular agent ethambutol were prepared and tested against Mycobacterium tuberculosis.
Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Ethambutol/chemical synthesis , Ethambutol/pharmacology , Antitubercular Agents/chemistry , Drug Design , Ethambutol/analogs & derivatives , Ethambutol/chemistry , Imines/chemistry , Models, Molecular , Molecular Conformation , Mycobacterium tuberculosis/drug effectsABSTRACT
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.
Subject(s)
Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glucosyltransferases/antagonists & inhibitors , Imino Sugars/chemistry , Imino Sugars/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Humans , Molecular Structure , Structure-Activity RelationshipABSTRACT
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.
