2. Academic Validation
  3. Mycophenolic acid analogs with a modified metabolic profile

Mycophenolic acid analogs with a modified metabolic profile

  • Bioorg Med Chem. 2008 Oct 15;16(20):9340-5. doi: 10.1016/j.bmc.2008.08.062.
Liqiang Chen 1,  Daniel J Wilson,  Nicholas P Labello,  Hiremagalur N Jayaram,  Krzysztof W Pankiewicz
Affiliations

Affiliation

  • 1 Center for Drug Design, Academic Health Center, University of Minnesota, 516 Delaware Street S.E., Minneapolis, MN 55455, USA. [email protected]
PMID: 18809333 DOI: 10.1016/j.bmc.2008.08.062
Abstract

Mycophenolic acid (MPA), a clinically used immunosuppressant, is extensively metabolized into an inactive C7-glucuronide and removed from circulation. To circumvent the metabolic liability imposed by the C7-hydroxyl group, we have designed a series of hybrid MPA analogs based on the pharmacophores present in MPA and new generations of inosine monophosphate dehydrogenase (IMPDH) inhibitors. The synthesis of MPA analogs has been accomplished by an allylic substitution of a common lactone. Biological evaluations of these analogs and a preliminary structure-activity relationship (SAR) are presented.

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