Display options
Cite
Gomtsyan A, McDonald HA, Schmidt RG, et al. TRPV1 ligands with hyperthermic, hypothermic and no temperature effects in rats. Temperature (Austin). 2015;2(2):297-301doi: 10.1080/23328940.2015.1046013.
Gomtsyan, A., McDonald, H. A., Schmidt, R. G., Daanen, J. F., Voight, E. A., Segreti, J. A., Puttfarcken, P. S., Reilly, R. M., Kort, M. E., Dart, M. J., & Kym, P. R. (2015). TRPV1 ligands with hyperthermic, hypothermic and no temperature effects in rats. Temperature (Austin, Tex.), 2(2), 297-301. https://doi.org/10.1080/23328940.2015.1046013
Gomtsyan, Arthur, et al. "TRPV1 ligands with hyperthermic, hypothermic and no temperature effects in rats." Temperature (Austin, Tex.) vol. 2,2 (2015): 297-301. doi: https://doi.org/10.1080/23328940.2015.1046013
Gomtsyan A, McDonald HA, Schmidt RG, Daanen JF, Voight EA, Segreti JA, Puttfarcken PS, Reilly RM, Kort ME, Dart MJ, Kym PR. TRPV1 ligands with hyperthermic, hypothermic and no temperature effects in rats. Temperature (Austin). 2015 May 22;2(2):297-301. doi: 10.1080/23328940.2015.1046013. eCollection 2015. PMID: 27227030; PMCID: PMC4843892.
Copy Download .nbib Format: NLM
Share it on

Temperature (Austin). 2015 May 22;2(2):297-301. doi: 10.1080/23328940.2015.1046013. eCollection 2015.

TRPV1 ligands with hyperthermic, hypothermic and no temperature effects in rats.

Temperature (Austin, Tex.)

Arthur Gomtsyan, Heath A McDonald, Robert G Schmidt, Jerome F Daanen, Eric A Voight, Jason A Segreti, Pamela S Puttfarcken, Regina M Reilly, Michael E Kort, Michael J Dart, Philip R Kym

Affiliations

  1. Research & Development; AbbVie Inc. ; Chicago, IL, USA.

PMID: 27227030 PMCID: PMC4843892 DOI: 10.1080/23328940.2015.1046013

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a multifunctional ion channel playing important roles in a numerous biological processes including the regulation of body temperature. Within distinct and tight chemical space of chromanyl ureas TRPV1 ligands were identified that exhibit distinctive pharmacology and a spectrum of thermoregulatory effects ranging from hypothermia to hyperthermia. The ability to manipulate these effects by subtle structural modifications of chromanyl ureas may serve as a productive approach in TRPV1 drug discovery programs addressing either side effect or desired target profiles of the compounds. Because chromanyl ureas in the TRPV1 context are generally antagonists, we verified observed partial agonist effects of a subset of compounds within that chemotype by comparing the in vitro profile of Compound 3 with known partial agonist 5'-I-RTX.

Keywords: 5′-I-RTX, 5′-iodo-resiniferatoxi; 5′-iodo-RTX; Compound 1, (R)-1-(2,2-dimethyl-7-(trifluoromethyl)chroman-4-yl)-3-(3,6-dimethylisoquinolin-5-yl)urea; Compound 2, (R)-1-(2,2-dimethyl-7-(trifluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea; Compound 3, (R)-1-(2,2-dimethyl-8-(trifluoromethoxy)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea; FLIPR, fluorometric imaging plate reader; OA, osteoarthritis; TRPV1; TRPV1 agonists; TRPV1 antagonists; TRPV1, transient receptor potential vanilloid 1; chromanyl ureas; hyperthermia; hypothermia; thermoregulation

References

  1. J Chem Inf Model. 2015 Mar 23;55(3):572-88 - PubMed
  2. J Pharmacol Exp Ther. 2012 Aug;342(2):416-28 - PubMed
  3. J Biol Chem. 2004 May 7;279(19):20283-95 - PubMed
  4. Biochemistry. 2004 Mar 9;43(9):2501-11 - PubMed
  5. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1338-41 - PubMed
  6. J Med Chem. 2014 Sep 11;57(17):7412-24 - PubMed
  7. J Pharmacol Exp Ther. 2005 Sep;314(3):1378-85 - PubMed
  8. Nature. 2000 May 11;405(6783):183-7 - PubMed
  9. Cell. 2002 Feb 8;108(3):421-30 - PubMed
  10. J Biol Chem. 2004 Apr 23;279(17):17165-72 - PubMed
  11. Nat Rev Drug Discov. 2007 May;6(5):357-72 - PubMed
  12. J Neurosci. 2010 Jan 27;30(4):1435-40 - PubMed
  13. Annu Rev Neurosci. 2001;24:487-517 - PubMed
  14. Science. 2000 Apr 14;288(5464):306-13 - PubMed
  15. Nat Rev Drug Discov. 2009 Jan;8(1):55-68 - PubMed
  16. Recent Pat CNS Drug Discov. 2013 Dec;8(3):180-204 - PubMed
  17. Nat Rev Neurosci. 2014 Sep;15(9):573-89 - PubMed
  18. Nature. 2013 Dec 5;504(7478):113-8 - PubMed
  19. Nature. 2013 Dec 5;504(7478):107-12 - PubMed
  20. J Pharmacol Exp Ther. 2002 Dec;303(3):1052-60 - PubMed
  21. Br J Pharmacol. 2004 Dec;143(8):1023-32 - PubMed
  22. Br J Pharmacol. 2003 Mar;138(5):977-85 - PubMed
  23. J Pharmacol Exp Ther. 2008 Jul;326(1):218-29 - PubMed
  24. Neurosci Lett. 2004 Nov 3;370(1):55-60 - PubMed
  25. Nature. 2001 Jun 21;411(6840):957-62 - PubMed
  26. Compr Physiol. 2012 Jan;2(1):563-608 - PubMed

Publication Types