Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Discovery of Novel TRPV1 Ligands through Rational Approach Based on Its Putative Endogenous Ligand, 12(S)-HPETE

  • Min, Kyung-Hoon (College of Pharmacy, Chung-Ang University) ;
  • Lee, Seul (College of Pharmacy, Chung-Ang University) ;
  • Kim, Hwa-Soon (Seoul Metropolitan Government Research Institute of Public Health and Environment) ;
  • Suh, Young-Ger (College of Pharmacy, Seoul National University)
  • Received : 2010.03.02
  • Accepted : 2010.03.31
  • Published : 2010.06.20
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Abstract

We report design and synthesis of the novel TRPV1 ligands through a rational approach. Simplified analogues of 12(S)-HPETE showing TRPV1 agonistic effect are disclosed. Biological evaluation revealed that substitution of functional groups without any change in conformation converted agonist into antagonist. Our work provided key information with regard to TRPV1 agonist/antagonist switching.

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References

  1. Szallasi, A.; Blumberg, P. M. Pharmacol. Rev. 1999, 51, 159-212.
  2. Szallasi, A.; Cortright, D. N.; Blum, C. A.; Eid, S. R. Nat. Rev. Drug Discov. 2007, 6, 357-372. https://doi.org/10.1038/nrd2280
  3. Bley, K. R. Expert Opin. Investig. Drugs 2004, 13, 1445-1456. https://doi.org/10.1517/13543784.13.11.1445
  4. Wood, J. Capsaicin in the Study of Pain; Academic press: San Diego, 1993.
  5. Gunthorpe, M. J.; Chizh, B. A. Drug Discov. Today 2009, 14, 1-2, 56-67. https://doi.org/10.1016/j.drudis.2008.11.005
  6. Pal, M.; Angaru, S.; Kodimuthali, A.; Dhingra, N.Curr. Pharm. Des. 2009, 15, 9, 1008-1026. https://doi.org/10.2174/138161209787581995
  7. Caterina, M. J.; Schumacher, M. A.; Tominaga, M.; Rosen, T.A.; Levine, J. D.; Julius, D. Nature 1997, 389, 816-824. https://doi.org/10.1038/39807
  8. Hwang, S. W.; Cho, H.; Kwak, J.; Lee, S. Y.; Kang, C. J.; Jung,J.; Cho, S.; Min, K. H.; Suh, Y. G.; Kim, D.; Oh, U. Proc. Natl. Acad. Sci. USA 2000, 97, 6155-6160. https://doi.org/10.1073/pnas.97.11.6155
  9. Corey. E. J.; William, S. Tetrahedron Lett. 1975, 16, 2647-2650. https://doi.org/10.1016/S0040-4039(00)75204-X
  10. Omura, K.; Swern, D. Tetrahedron 1978, 34(11), 1651-1660. https://doi.org/10.1016/0040-4020(78)80197-5
  11. Just, G.; Singh, R. Tetrahedron Lett. 1987, 28, 5981-5984. https://doi.org/10.1016/S0040-4039(00)96842-4

Cited by

  1. ChemInform Abstract: Discovery of Novel TRPV1 Ligands Through Rational Approach Based on Its Putative Endogenous Ligand, 12(S)-HPETE. vol.41, pp.45, 2010, https://doi.org/10.1002/chin.201045079