Novel Fubinaca/Rimonabant hybrids as endocannabinoid system modulators

Amino Acids
Azzurra StefanucciAdriano Mollica

Abstract

The discovery of novel modulators of the cannabinoid system is a current topic in medicinal chemistry. In this paper, we report nine novel carboxamides designed as hybrids of Fubinaca family compounds and Rimonabant. These hybrids were obtained by linking the 1-benzyl-2,5-dichloroindazole-3-carboxylic acid to different amino acids bearing a hydrophobic side chain and three different C-terminus. The new chemical entities were tested in vitro to evaluate their bioactivity by means of receptor binding assays and [35S]GTPγS stimulation assays to reveal their affinity and potency. We found that all compounds were able to bind to the cannabinoid receptors in the low nanomolar range with a marked selectivity towards the CB1 cannabinoid receptor. Some of them are full agonists, whereas the others act as partial agonists. These molecules could be potentially used as anti-obesity agents, antiemetic and analgesics.

References

Jan 1, 1984·Oncology·A Caputo, B Silvestrini
Jul 12, 2005·Bioorganic & Medicinal Chemistry Letters·John W HuffmanBilly R Martin
Mar 5, 2013·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Axel RomingerOliver Pogarell
Oct 12, 2013·Life Sciences·Anita H LewinP Anantha Reddy
Mar 3, 2015·The Journal of Emergency Medicine·Michael D SchwartzRoy R Gerona
Jul 15, 2015·The New England Journal of Medicine·Jordan TreckiMichael D Schwartz
Aug 13, 2015·Bioorganic & Medicinal Chemistry·Adriano MollicaClaudiu T Supuran
Jan 18, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Adriano MollicaRomano Silvestri

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Citations

Jan 31, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Giulio PoliCarlotta Granchi
Mar 13, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yu TianXu-Dong Xu
Feb 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Günter A MüllerTimo D Müller
Dec 29, 2019·International Journal of Molecular Sciences·Giulia ZuccariniGiorgio Roberto Merlo
May 9, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Alexandru SavaLenuţa Profire
Jul 3, 2021·International Journal of Molecular Sciences·Tatiana WojciechowiczMarek Skrzypski
Aug 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Marilisa Pia DimmitoAdriano Mollica

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Methods Mentioned

BETA
column chromatography
competition binding

Software Mentioned

GraphPad Prism

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