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

Dominik REJMAN; Magda OLESIAK; LIQIANG LIQIANG CHEN; Steven E PATTERSON; Daniel WILSON; Hiramagalur N JAYARAM; Lizbeth HEDSTROM; Krzysztof W PANKIEWICZ

doi:10.1021/jm060479r

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

Journal article

Peer reviewed

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

Dominik REJMAN, Magda OLESIAK, LIQIANG LIQIANG CHEN, Steven E PATTERSON, Daniel WILSON, Hiramagalur N JAYARAM, Lizbeth HEDSTROM and Krzysztof W PANKIEWICZ

Journal of Medicinal Chemistry, Vol.49(16), pp.5018-5022

2006

DOI: https://doi.org/10.1021/jm060479r

PMID: 16884314

Abstract

Biological and medical sciences

General aspects

Medical sciences

Pharmacology. Drug treatments

Antineoplastic Agents

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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Title: Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. inhibition of inosine monophosphate dehydrogenase
Creators: Dominik REJMAN - Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, United States
Magda OLESIAK - Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, United States
LIQIANG LIQIANG CHEN - Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, United States
Steven E PATTERSON - Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, United States
Daniel WILSON - Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, United States
Hiramagalur N JAYARAM - Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Richard Roudebush Veterans Affairs Medical Center, 1481 West Tenth Street, Indianapolis, Indiana 46202, United States
Lizbeth HEDSTROM - Department of Biochemistry, MS009, Brandeis University, Waltham, Massachusetts 02454, United States
Krzysztof W PANKIEWICZ - Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, United States
Publication Details: Journal of Medicinal Chemistry, Vol.49(16), pp.5018-5022
Publisher: American Chemical Society; Washington, DC
Identifiers: 9923957922801921
Academic Unit: Department of Biology; Department of Chemistry
Language: English
Resource Type: Journal article

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

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