Synthesis of sulfone-based nucleotide isosteres: identification of CMP-sialic acid synthetase inhibitors.
A modular replacement approach to the synthesis of sulfo-nucleotide analogs prepared from condensation of nucleoside aldehydes with bis phosphonate Horner-Wadsworth-Emmons reagents is disclosed. These analogs were shown to be inhibitors of Neisseria meningitidis CSS (NmCSS), which is a key enzyme in the biosynthesis of the capsular polysaccharides required for bacterial infection.
Wong
Jessica H
JH
Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA, USA.
Sahni
Urvashi
U
Li
Yanhong
Y
Chen
Xi
X
Gervay-Hague
Jacquelyn
J
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003593:Cytoplasm / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D000216:N-Acylneuraminate Cytidylyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D009345:Neisseria meningitidis / Q000201:enzymology; D009711:Nucleotides / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry*
D004791:Enzyme Inhibitors; D009711:Nucleotides; D011134:Polysaccharides; D013450:Sulfones; D000216:N-Acylneuraminate Cytidylyltransferase