A series of novel acylide derivatives have been synthesized from clarithromyc｜n A via a tacile procedure. The C-3 modifications involved replacing the natural C-3 cladinosyl group in clarithromycin core with differen...A series of novel acylide derivatives have been synthesized from clarithromyc｜n A via a tacile procedure. The C-3 modifications involved replacing the natural C-3 cladinosyl group in clarithromycin core with different aryl-piperzine sidechain via chemical synthesis, Meanwhile a distinctive intermediate with 10,11-epoxy moiety was obtained, The structure and stereochemistry of this novel structure were confirmed via NMR and X-ray crystallography. Potential anti-bacterial activities against both Grampositive and Gram-negative bacteria were reported. Because of existence of C10,11-epoxide, these derivatives can be used as intermediates for further structural modification.展开更多
Ligand-and structure-based virtual screening methods were employed to identify novel non-hydroxamate histone deacetylase(HDAC)inhibitors.Based on the newly identified hit compound 17a,three series of compounds were sy...Ligand-and structure-based virtual screening methods were employed to identify novel non-hydroxamate histone deacetylase(HDAC)inhibitors.Based on the newly identified hit compound 17a,three series of compounds were synthesized and evaluated for both HDAC1 inhibitory activity and cytotoxicity.Binding modes of representative structures were analyzed using the docking method to explain the observed disparity in HDAC1 inhibitory activities.展开更多
基金supported by Jiangsu Hengrui Pharmaceutical Company.The X-ray crystallography was performed at Shanghai Institute of Organic Chemistry,China Academy of Science
文摘A series of novel acylide derivatives have been synthesized from clarithromyc｜n A via a tacile procedure. The C-3 modifications involved replacing the natural C-3 cladinosyl group in clarithromycin core with different aryl-piperzine sidechain via chemical synthesis, Meanwhile a distinctive intermediate with 10,11-epoxy moiety was obtained, The structure and stereochemistry of this novel structure were confirmed via NMR and X-ray crystallography. Potential anti-bacterial activities against both Grampositive and Gram-negative bacteria were reported. Because of existence of C10,11-epoxide, these derivatives can be used as intermediates for further structural modification.
文摘Ligand-and structure-based virtual screening methods were employed to identify novel non-hydroxamate histone deacetylase(HDAC)inhibitors.Based on the newly identified hit compound 17a,three series of compounds were synthesized and evaluated for both HDAC1 inhibitory activity and cytotoxicity.Binding modes of representative structures were analyzed using the docking method to explain the observed disparity in HDAC1 inhibitory activities.
