Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase

Dominik Rejman, Magda Olesiak, Liqiang Chen, Steven E. Patterson, Daniel Wilson, Hiramagalur N. Jayaram, Lizbeth Hedstrom, Krzysztof W. Pankiewicz

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide (MAD) have been prepared as potential inhibitors of IMP dehydrogenase. A coupling of the mycophenolic (hydroxymethyl)-phosphonate 6 with the phosphitylated adenosine analogue 11 followed by oxidation and deprotection afforded the phosphophosphonate 8. A similar coupling between adenosine (hydroxymethyl)phosphonate 10 and phosphitylated mycophenolic alcohol 5 gave the corresponding phosphophosphonate 13. Both 8 and 13 (Ki = 20-87 nM) were found to be the most potent cofactor type inhibitors of IMP dehydrogenase.

Original languageEnglish
Pages (from-to)5018-5022
Number of pages5
JournalJournal of Medicinal Chemistry
Volume49
Issue number16
DOIs
StatePublished - Aug 10 2006

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IMP Dehydrogenase
Inosine Monophosphate
Organophosphonates
Adenosine
Oxidoreductases
Alcohols
Oxidation
mycophenolic adenine dinucleotide

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Rejman, D., Olesiak, M., Chen, L., Patterson, S. E., Wilson, D., Jayaram, H. N., ... Pankiewicz, K. W. (2006). Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase. Journal of Medicinal Chemistry, 49(16), 5018-5022. https://doi.org/10.1021/jm060479r

Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase. / Rejman, Dominik; Olesiak, Magda; Chen, Liqiang; Patterson, Steven E.; Wilson, Daniel; Jayaram, Hiramagalur N.; Hedstrom, Lizbeth; Pankiewicz, Krzysztof W.

In: Journal of Medicinal Chemistry, Vol. 49, No. 16, 10.08.2006, p. 5018-5022.

Research output: Contribution to journalArticle

Rejman, D, Olesiak, M, Chen, L, Patterson, SE, Wilson, D, Jayaram, HN, Hedstrom, L & Pankiewicz, KW 2006, 'Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase', Journal of Medicinal Chemistry, vol. 49, no. 16, pp. 5018-5022. https://doi.org/10.1021/jm060479r
Rejman, Dominik ; Olesiak, Magda ; Chen, Liqiang ; Patterson, Steven E. ; Wilson, Daniel ; Jayaram, Hiramagalur N. ; Hedstrom, Lizbeth ; Pankiewicz, Krzysztof W. / Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 16. pp. 5018-5022.
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AU - Pankiewicz, Krzysztof W.

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