Pyrazoles with a "click" 4-[N-(4-fluorobutyl)-1,2,3-triazole] substituent in position 3 are nanomolar CB1 receptor ligands

Rita Distinto, Chiara Zanato, Serena Montanari, Maria Grazia Cascio, Paolo Lazzari, Roger Pertwee, Matteo Zanda*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)184-191
Number of pages8
JournalJournal of Fluorine Chemistry
Volume167
Early online date21 Jul 2014
DOIs
Publication statusPublished - Nov 2014

Fingerprint

rimonabant
Pyrazoles
Cannabinoid Receptor CB1
Triazoles
ligand
replacement
Ligands
ligands
selectivity
Imaging techniques
molecules
Molecules

Keywords

  • "Click" chemistry
  • Cannabinoids
  • Fluorine
  • PET imaging
  • Sonogashira reaction

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Environmental Chemistry

Cite this

Pyrazoles with a "click" 4-[N-(4-fluorobutyl)-1,2,3-triazole] substituent in position 3 are nanomolar CB1 receptor ligands. / Distinto, Rita; Zanato, Chiara; Montanari, Serena; Cascio, Maria Grazia; Lazzari, Paolo; Pertwee, Roger; Zanda, Matteo.

In: Journal of Fluorine Chemistry, Vol. 167, 11.2014, p. 184-191.

Research output: Contribution to journalArticle

Distinto, Rita ; Zanato, Chiara ; Montanari, Serena ; Cascio, Maria Grazia ; Lazzari, Paolo ; Pertwee, Roger ; Zanda, Matteo. / Pyrazoles with a "click" 4-[N-(4-fluorobutyl)-1,2,3-triazole] substituent in position 3 are nanomolar CB1 receptor ligands. In: Journal of Fluorine Chemistry. 2014 ; Vol. 167. pp. 184-191.
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abstract = "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.",
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author = "Rita Distinto and Chiara Zanato and Serena Montanari and Cascio, {Maria Grazia} and Paolo Lazzari and Roger Pertwee and Matteo Zanda",
note = "Acknowledgments 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.",
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T1 - Pyrazoles with a "click" 4-[N-(4-fluorobutyl)-1,2,3-triazole] substituent in position 3 are nanomolar CB1 receptor ligands

AU - Distinto, Rita

AU - Zanato, Chiara

AU - Montanari, Serena

AU - Cascio, Maria Grazia

AU - Lazzari, Paolo

AU - Pertwee, Roger

AU - Zanda, Matteo

N1 - Acknowledgments 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.

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