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

doi:10.1016/j.jfluchem.2014.07.010

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 journal › Article › peer-review

5 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 K_i = 23 nM for CB₁, which is very close to that displayed by Rimonabant (SR141716), and fairly good CB₁/CB₂ selectivity (K_i CB₂/K_i CB₁ = 35.5), thus representing a promising candidate for [¹⁸F]radiolabeling and PET Imaging studies of the CB₁ receptor.

Original language	English
Pages (from-to)	184-191
Number of pages	8
Journal	Journal of Fluorine Chemistry
Volume	167
Early online date	21 Jul 2014
DOIs	https://doi.org/10.1016/j.jfluchem.2014.07.010
Publication status	Published - Nov 2014

Bibliographical 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.

Keywords

"Click" chemistry
Cannabinoids
Fluorine
PET imaging
Sonogashira reaction

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10.1016/j.jfluchem.2014.07.010

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

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.",

keywords = "{"}Click{"} chemistry, Cannabinoids, Fluorine, PET imaging, Sonogashira reaction",

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.",

year = "2014",

month = nov,

doi = "10.1016/j.jfluchem.2014.07.010",

language = "English",

volume = "167",

pages = "184--191",

journal = "Journal of Fluorine Chemistry",

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TY - JOUR

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.

PY - 2014/11

Y1 - 2014/11

N2 - 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.

AB - 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.

KW - "Click" chemistry

KW - Cannabinoids

KW - Fluorine

KW - PET imaging

KW - Sonogashira reaction

UR - http://www.scopus.com/inward/record.url?scp=85027936857&partnerID=8YFLogxK

U2 - 10.1016/j.jfluchem.2014.07.010

DO - 10.1016/j.jfluchem.2014.07.010

M3 - Article

AN - SCOPUS:85027936857

SN - 0022-1139

VL - 167

SP - 184

EP - 191

JO - Journal of Fluorine Chemistry

JF - Journal of Fluorine Chemistry

ER -

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

Abstract

Bibliographical note

Keywords

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