Replacement of the 3-carbonylaminopiperidine substitutent with a "click" 4-[N-(4-fluorobutyl)-(1,2,3-triazolyl)] group in Rimonabant-type pyrazoles produced a novel class of nanomolar CB1 receptor ligands. Molecule 1d is the most promising lead with a Ki = 23 nM for CB1, which is very close to that displayed by Rimonabant (SR141716), and fairly good CB1/CB2 selectivity (Ki CB2/Ki CB1 = 35.5), thus representing a promising candidate for [18F]radiolabeling and PET Imaging studies of the CB1 receptor.
We thank the European Commission for financial support (Industry Academia Partnerships and Pathways project “PET BRAIN”, Contract No 251482) and the EPSRC National Mass Spectrometry Service Centre (Swansea, UK), for performing HRMS analyses.
- "Click" chemistry
- PET imaging
- Sonogashira reaction