Synthesis, molecular modeling and biological evaluation of aza-proline and aza-pipecolic derivatives as FKBP12 ligands and their in vivo neuroprotective effects

Douglas E. Wilkinson, Bert E. Thomas IV, David C. Limburg, Agnes Holmes, Hansjorg Sauer, Douglas T. Ross, Raj Soni, Yi Chen, Hong Guo, Pamela Howorth, Heather Valentine, Dawn Spicer, Mike Fuller, Joseph P. Steiner, Gregory S. Hamilton, Yong Qian Wu

Research output: Contribution to journalArticlepeer-review

Abstract

Nonimmunosuppressant ligands, exemplified by GPI 1046 (1), for the peptidyl-prolyl isomerase FKBP12 have been found to unexpectedly possess powerful neuroprotective and neuroregenerative effects in vitro and in vivo. We have extensively explored the therapeutic utility of FKBP12 ligands based on analogues of proline and pipecolic acid. As part of our ongoing program to explore novel structural classes of FKBP12 ligands, we herein wish to report a new class of FKBP12 ligands containing aza-proline and aza-pipecolic acid analogues. Details of the synthetic studies, together with biological activity will be presented.

Original languageEnglish (US)
Pages (from-to)4815-4825
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume11
Issue number22
DOIs
StatePublished - Nov 1 2003

ASJC Scopus subject areas

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

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