Mycophenolic acid analogs with a modified metabolic profile

Liqiang Chen, Daniel J. Wilson, Nicholas P. Labello, Hiremagalur N. Jayaram, Krzysztof W. Pankiewicz

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9340-9345
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number20
DOIs
StatePublished - Oct 15 2008

Fingerprint

Mycophenolic Acid
Metabolome
Inosine Monophosphate
Glucuronides
Lactones
Structure-Activity Relationship
Immunosuppressive Agents
Hydroxyl Radical
Oxidoreductases
Substitution reactions

Keywords

  • Allylic substitution
  • Inosine monophosphate dehydrogenase
  • Mycophenolic acid

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Chen, L., Wilson, D. J., Labello, N. P., Jayaram, H. N., & Pankiewicz, K. W. (2008). Mycophenolic acid analogs with a modified metabolic profile. Bioorganic and Medicinal Chemistry, 16(20), 9340-9345. https://doi.org/10.1016/j.bmc.2008.08.062

Mycophenolic acid analogs with a modified metabolic profile. / Chen, Liqiang; Wilson, Daniel J.; Labello, Nicholas P.; Jayaram, Hiremagalur N.; Pankiewicz, Krzysztof W.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 20, 15.10.2008, p. 9340-9345.

Research output: Contribution to journalArticle

Chen, L, Wilson, DJ, Labello, NP, Jayaram, HN & Pankiewicz, KW 2008, 'Mycophenolic acid analogs with a modified metabolic profile', Bioorganic and Medicinal Chemistry, vol. 16, no. 20, pp. 9340-9345. https://doi.org/10.1016/j.bmc.2008.08.062
Chen L, Wilson DJ, Labello NP, Jayaram HN, Pankiewicz KW. Mycophenolic acid analogs with a modified metabolic profile. Bioorganic and Medicinal Chemistry. 2008 Oct 15;16(20):9340-9345. https://doi.org/10.1016/j.bmc.2008.08.062
Chen, Liqiang ; Wilson, Daniel J. ; Labello, Nicholas P. ; Jayaram, Hiremagalur N. ; Pankiewicz, Krzysztof W. / Mycophenolic acid analogs with a modified metabolic profile. In: Bioorganic and Medicinal Chemistry. 2008 ; Vol. 16, No. 20. pp. 9340-9345.
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