PSNCBAM-1 analogs: Structural evolutions and allosteric properties at cannabinoid CB1 receptor.


Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
01 Oct 2020
Historique:
received: 15 04 2020
revised: 17 06 2020
accepted: 18 06 2020
pubmed: 19 7 2020
medline: 23 4 2021
entrez: 19 7 2020
Statut: ppublish

Résumé

Allosteric modulation of the CB1Rs could represent an alternative strategy for the treatment of diseases in which these receptors are involved, without the undesirable effects associated with their orthosteric stimulation. PSNCBAM-1 is a reference diaryl urea derivative that positively affects the binding affinity of orthosteric ligands (PAM) and negatively affects the functional activity of orthosteric ligands (NAM) at CB1Rs. In this work we reported the design, synthesis and biological evaluation of three different series of compounds, derived from structural modifications of PSNCBAM-1 and its analogs reported in the recent literature. Almost all the new compounds increased the percentage of binding affinity of CP55940 at CB1Rs, showing a PAM profile. When tested alone in the [

Identifiants

pubmed: 32682199
pii: S0223-5234(20)30578-X
doi: 10.1016/j.ejmech.2020.112606
pii:
doi:

Substances chimiques

1-(4-chlorophenyl)-3-(3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl)urea 0
Ligands 0
Phenylurea Compounds 0
Pyridines 0
Receptor, Cannabinoid, CB1 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

112606

Informations de copyright

Copyright © 2020 Elsevier Masson SAS. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no competing financial interest.

Auteurs

Serena Meini (S)

Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.

Francesca Gado (F)

Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.

Lesley A Stevenson (LA)

School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD Aberdeen, Scotland, UK.

Maria Digiacomo (M)

Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.

Alessandro Saba (A)

Department of Surgical Pathology, Molecular Medicine and of the Critical Area, University of Pisa, Via Savi 10, 56126, Pisa, Italy.

Simone Codini (S)

Department of Surgical Pathology, Molecular Medicine and of the Critical Area, University of Pisa, Via Savi 10, 56126, Pisa, Italy.

Marco Macchia (M)

Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.

Roger G Pertwee (RG)

School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD Aberdeen, Scotland, UK.

Simone Bertini (S)

Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy. Electronic address: simone.bertini@unipi.it.

Clementina Manera (C)

Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.

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Classifications MeSH