Novel Fubinaca/Rimonabant hybrids as endocannabinoid system modulators

Stefanucci, Azzurra and Macedonio, Giorgia and Dvorácskó, Szabolcs and Tömböly, Csaba and Mollica, Adriano (2018) Novel Fubinaca/Rimonabant hybrids as endocannabinoid system modulators. AMINO ACIDS, 50 (11). pp. 1595-1605. ISSN 0939-4451

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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 [S-35]GTPS 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.

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