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Design, Synthesis and Biological Evaluation of Novel Non-Peptide Opioid Ligands for Human Pain

  • Xuejun Tang
  • Xuyuan Gu
  • Jinfa Ying
  • Vadim A. Soloshonok
  • Victor J. Hruby
Part of the American Peptide Symposia book series (APSY, volume 7)

Abstract

To find therapeutics for human pain with efficacy but without the side effects which accompany morphine-related drugs is a critical need. Based on extensive structure-activity studies of cyclic enkaphalins, we have designed and synthesized a series of conformationally constrained peptide analogues such as [(2S,3R)-TMT1]-DPDPE, which are essentially specific for the δ-opioid receptor [1]. Aiming to transfer the pharmacophores in these peptide ligands to a non-peptide scaffold and to maintain the high binding affinity and biological activities at the δ-receptor, first and second generation non-peptide ligands were successfully designed with the aid of computer modeling [2,3]. In an effort to optimize these ligands, we present some newly designed ligands such as 6–11 that are based on computer modeling and our understanding of current successful examples like SL-3111.

Keywords

High Binding Affinity Biological Evaluation Peptide Ligand Phenol Ring Effective Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Hruby, V.J., Yumamura, H.I., Porreca, F. Ann. N.Y. Acad. Sci. 757, 7 (1995).PubMedCrossRefGoogle Scholar
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    Liao, S., Alfaro-Lopez, J., Shendrovich, M.D., Hosohata, K., Yumamura, H.I., Hruby, V.J. J. Med. Chem. 41, 4767 (1998).PubMedCrossRefGoogle Scholar
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    Alfaro-Lopez, J., Okayama, T., Hosohata, K., Davis, P., Porreca, F., Yamamura, H.I., Hruby, V.J. J. Med. Chem. 42, 5359 (1999).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • Xuejun Tang
    • 1
  • Xuyuan Gu
    • 1
  • Jinfa Ying
    • 1
  • Vadim A. Soloshonok
    • 1
  • Victor J. Hruby
    • 1
  1. 1.Department of ChemistryUniversity of ArizonaTucsonUSA

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