4-Cyano-5-(2-Thiophenyl)-Pyrazoles are High Affinity CB1 Receptor Ligands

Stefano Altomonte, Gemma Louise Baillie, Ruth Ross, Matteo Zanda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Pyrazoles bearing a 5-thiophenyl and a 4-cyano group were synthesised and tested for their affinity to the cannabinoid CB1 receptor showing in many cases single digit nanomolar Ki values and moderate to good selectivity towards the CB2 receptor. Some of these pyrazole ligands, such as 8g, displayed relatively low lipophilicity (experimental logP < 4) and high calculated Topological Polar Surface Area (TPSA) (>90) suggesting that these compounds may behave as peripherally restricted CB1 ligands. Furthermore, 2-fluoroethyl carboxamides 8d, 8h and 8l are interesting candidates for further development into PET tracers.
Original languageEnglish
Pages (from-to)13692-13701
Number of pages10
JournalRSC Advances
Volume5
Issue number18
Early online date21 Jan 2015
DOIs
Publication statusPublished - 2015

Fingerprint

Pyrazoles
Cannabinoid Receptor CB1
Bearings (structural)
Ligands
Cannabinoid Receptor CB2

Keywords

  • 4-Cyano-5-(2-thiophenyl)-pyrazoles
  • CB1 receptor ligands
  • Cannabinoid receptors
  • CB1 receptor
  • CB1 ligands

Cite this

Altomonte, S., Baillie, G. L., Ross, R., & Zanda, M. (2015). 4-Cyano-5-(2-Thiophenyl)-Pyrazoles are High Affinity CB1 Receptor Ligands. RSC Advances, 5(18), 13692-13701. https://doi.org/10.1039/C4RA17274D

4-Cyano-5-(2-Thiophenyl)-Pyrazoles are High Affinity CB1 Receptor Ligands. / Altomonte, Stefano; Baillie, Gemma Louise; Ross, Ruth; Zanda, Matteo.

In: RSC Advances, Vol. 5, No. 18, 2015, p. 13692-13701.

Research output: Contribution to journalArticle

Altomonte, S, Baillie, GL, Ross, R & Zanda, M 2015, '4-Cyano-5-(2-Thiophenyl)-Pyrazoles are High Affinity CB1 Receptor Ligands', RSC Advances, vol. 5, no. 18, pp. 13692-13701. https://doi.org/10.1039/C4RA17274D
Altomonte, Stefano ; Baillie, Gemma Louise ; Ross, Ruth ; Zanda, Matteo. / 4-Cyano-5-(2-Thiophenyl)-Pyrazoles are High Affinity CB1 Receptor Ligands. In: RSC Advances. 2015 ; Vol. 5, No. 18. pp. 13692-13701.
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abstract = "Pyrazoles bearing a 5-thiophenyl and a 4-cyano group were synthesised and tested for their affinity to the cannabinoid CB1 receptor showing in many cases single digit nanomolar Ki values and moderate to good selectivity towards the CB2 receptor. Some of these pyrazole ligands, such as 8g, displayed relatively low lipophilicity (experimental logP < 4) and high calculated Topological Polar Surface Area (TPSA) (>90) suggesting that these compounds may behave as peripherally restricted CB1 ligands. Furthermore, 2-fluoroethyl carboxamides 8d, 8h and 8l are interesting candidates for further development into PET tracers.",
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