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

doi:10.1016/S0968-0896(03)00478-4

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

School of Medicine

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

19 Scopus citations

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 language	English (US)
Pages (from-to)	4815-4825
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	11
Issue number	22
DOIs	https://doi.org/10.1016/S0968-0896(03)00478-4
State	Published - Nov 1 2003

ASJC Scopus subject areas

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

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10.1016/S0968-0896(03)00478-4

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Wilkinson, D. E., Thomas IV, B. E., Limburg, D. C., Holmes, A., Sauer, H., Ross, D. T., Soni, R., Chen, Y., Guo, H., Howorth, P., Valentine, H., Spicer, D., Fuller, M., Steiner, J. P., Hamilton, G. S., & Wu, Y. Q. (2003). Synthesis, molecular modeling and biological evaluation of aza-proline and aza-pipecolic derivatives as FKBP12 ligands and their in vivo neuroprotective effects. Bioorganic and Medicinal Chemistry, 11(22), 4815-4825. https://doi.org/10.1016/S0968-0896(03)00478-4

Synthesis, molecular modeling and biological evaluation of aza-proline and aza-pipecolic derivatives as FKBP12 ligands and their in vivo neuroprotective effects. / Wilkinson, Douglas E.; Thomas IV, Bert E.; Limburg, David C. et al.
In: Bioorganic and Medicinal Chemistry, Vol. 11, No. 22, 01.11.2003, p. 4815-4825.

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

Wilkinson, DE, Thomas IV, BE, Limburg, DC, Holmes, A, Sauer, H, Ross, DT, Soni, R, Chen, Y, Guo, H, Howorth, P, Valentine, H, Spicer, D, Fuller, M, Steiner, JP, Hamilton, GS & Wu, YQ 2003, 'Synthesis, molecular modeling and biological evaluation of aza-proline and aza-pipecolic derivatives as FKBP12 ligands and their in vivo neuroprotective effects', Bioorganic and Medicinal Chemistry, vol. 11, no. 22, pp. 4815-4825. https://doi.org/10.1016/S0968-0896(03)00478-4

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

Abstract

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