Function-oriented synthesis of simplified caprazamycins: discovery of oxazolidine-containing uridine derivatives as antibacterial agents against drug-...
Basic Information
ID: ALA1157746
Journal: J Med Chem
Title: Function-oriented synthesis of simplified caprazamycins: discovery of oxazolidine-containing uridine derivatives as antibacterial agents against drug-resistant bacteria.
Authors: Ii K, Ichikawa S, Al-Dabbagh B, Bouhss A, Matsuda A.
Abstract: The rational simplification of the caprazamycin (CPZ) class of nucleoside natural products was carried out to address their molecular complexity. First, analogues 6-8, where the diazepanone ring of the CPZ was removed and a lipophilic side chain was attached to either the C-7' or N(6') atom, were used to investigate the conformation-activity relationship. On the basis of this relationship, we designed the oxazolidine-containing uridine derivatives 18-21 by restricting the conformation of 6-8. As a result, the (t)Bu ester derivatives 20 were found to be the most active against a range of bacterial strains containing VRE with a potency similar to that of the parent CPZs. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria.
CiteXplore: 20405928
DOI: 10.1021/jm100243n
Patent ID: ┄