Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor.
A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration.
Chen
Liqiang
L
Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA. chenx462@umn.edu
Gao
Guangyao
G
Bonnac
Laurent
L
Wilson
Daniel J
DJ
Bennett
Eric M
EM
Jayaram
Hiremagalur N
HN
Pankiewicz
Krzysztof W
KW
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009243:NAD / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry
D004791:Enzyme Inhibitors; D013449:Sulfonamides; C521565:methylenebis(sulfonamide); D009243:NAD; D007168:IMP Dehydrogenase