ABSTRACT
2-Azetidinones, commonly known as beta-lactams, are well-known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel beta-lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform-selectivity of these compounds towards HDAC6 and HDAC8. The isoform selectivity changed in response to modification of the azetidinone-ring nitrogen atom substituent. The presence of an N-thiomethyl group is a prerequisite for the activity of these compounds in the micromolar range towards HDAC8.
Subject(s)
Azetidines/chemistry , Azetidines/pharmacology , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Zinc/metabolism , Azetidines/chemical synthesis , Histone Deacetylase Inhibitors/chemical synthesis , Histone Deacetylases/chemistry , Humans , Models, Molecular , Molecular Structure , Protein Binding , Protein Isoforms/chemistry , Protein Isoforms/metabolism , Structure-Activity RelationshipABSTRACT
Remarkable generality in scope of DATs/Cu catalysts for enantioselective nitroaldol reaction is described; excellent levels of stereoinduction are recorded for a range of aldehydes (ee 81-99%, 17 examples) and the possibility to employ the present catalytic system as the key step for the preparation of highly functionalized tetrahydro-isoquinolines is demonstrated.
