Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor

Liqiang Chen, Guangyao Gao, Laurent Bonnac, Daniel J. Wilson, Eric M. Bennett, Hiremagalur N. Jayaram, Krzysztof W. Pankiewicz

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3152-3155
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number11
DOIs
StatePublished - Jun 1 2007

Fingerprint

Inosine Monophosphate
NAD
Oxidoreductases
Sulfonamides
Nucleosides
methylenebis(sulfonamide)

Keywords

  • IMPDH
  • Inosine monophosphate dehydrogenase
  • Methylenebis(sulfonamide)
  • NAD analogue
  • Pyrophosphate mimics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor. / Chen, Liqiang; Gao, Guangyao; Bonnac, Laurent; Wilson, Daniel J.; Bennett, Eric M.; Jayaram, Hiremagalur N.; Pankiewicz, Krzysztof W.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 11, 01.06.2007, p. 3152-3155.

Research output: Contribution to journalArticle

Chen, Liqiang ; Gao, Guangyao ; Bonnac, Laurent ; Wilson, Daniel J. ; Bennett, Eric M. ; Jayaram, Hiremagalur N. ; Pankiewicz, Krzysztof W. / Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 11. pp. 3152-3155.
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