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.
- CB1 receptor ligands
- Cannabinoid receptors
- CB1 receptor
- CB1 ligands
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