Novel Fubinaca/Rimonabant hybrids as endocannabinoid system modulators

Azzurra Stefanucci, Giorgia Macedonio, Szabolcs Dvorácskó, C. Tömböly, Adriano Mollica

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1595-1605
Number of pages11
JournalAmino Acids
Volume50
Issue number11
DOIs
Publication statusPublished - Nov 1 2018

Keywords

  • Amino acids
  • Cannabinoid receptors
  • Cannabinoids
  • Lonidamine
  • Selectivity

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Stefanucci, A., Macedonio, G., Dvorácskó, S., Tömböly, C., & Mollica, A. (2018). Novel Fubinaca/Rimonabant hybrids as endocannabinoid system modulators. Amino Acids, 50(11), 1595-1605. https://doi.org/10.1007/s00726-018-2636-1