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

doi:10.1021/jm060479r

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

Center for Drug Design

Research output: Contribution to journal › Article › peer-review

22 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 (K_i = 20-87 nM) were found to be the most potent cofactor type inhibitors of IMP dehydrogenase.

Original language	English (US)
Pages (from-to)	5018-5022
Number of pages	5
Journal	Journal of medicinal chemistry
Volume	49
Issue number	16
DOIs	https://doi.org/10.1021/jm060479r
State	Published - Aug 10 2006

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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.",

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T1 - Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase

AU - Rejman, Dominik

AU - Olesiak, Magda

AU - Chen, Liqiang

AU - Patterson, Steven E.

AU - Wilson, Daniel

AU - Jayaram, Hiramagalur N.

AU - Hedstrom, Lizbeth

AU - Pankiewicz, Krzysztof W.

PY - 2006/8/10

Y1 - 2006/8/10

N2 - 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.

AB - 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.

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

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