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 journalArticlepeer-review

21 Scopus citations

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 (US)
Pages (from-to)5018-5022
Number of pages5
JournalJournal of medicinal chemistry
Volume49
Issue number16
DOIs
StatePublished - Aug 10 2006

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