New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo (2023)

Brizzi, A., Brizzi, V., Cascio, M. G., Corelli, F., Guida, F., Ligresti, A., Maione, S., Martinelli, A., Pasquini, S., Tuccinardi, T., & Di Marzo, V. (2009). New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo. Journal of Medicinal Chemistry, 52(8), 2506-2514. https://doi.org/10.1021/jm8016255

New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo. / Brizzi, Antonella; Brizzi, Vittorio; Cascio, Maria Grazia et al.

In: Journal of Medicinal Chemistry, Vol. 52, No. 8, 23.04.2009, p. 2506-2514.

Research output: Contribution to journal › Article › peer-review

Brizzi, A, Brizzi, V, Cascio, MG, Corelli, F, Guida, F, Ligresti, A, Maione, S, Martinelli, A, Pasquini, S, Tuccinardi, T & Di Marzo, V 2009, 'New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo', Journal of Medicinal Chemistry, vol. 52, no. 8, pp. 2506-2514. https://doi.org/10.1021/jm8016255

Brizzi A, Brizzi V, Cascio MG, Corelli F, Guida F, Ligresti A et al. New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo. Journal of Medicinal Chemistry. 2009 Apr 23;52(8):2506-2514. Epub 2009 Mar 30. doi: 10.1021/jm8016255

Brizzi, Antonella ; Brizzi, Vittorio ; Cascio, Maria Grazia et al. / New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo. In: Journal of Medicinal Chemistry. 2009 ; Vol. 52, No. 8. pp. 2506-2514.

@article{b2a3fc1869f64ef5b841ff76ffc816a0,

title = "New resorcinol-anandamide {"}hybrids{"} as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo",

abstract = "Bearing in mind the pharmacophoric requirements of both (-)-trans-Δ 9-tetrahydrocannabinol (THC) and anandamide (AEA), we designed a novel pharmacophore consisting of both a rigid aromatic backbone and a flexible chain with the aim to develop a series of stable and potent ligands of cannabinoid receptors. In this paper we report the synthesis, docking studies, and structure-activity relationships of new resorcinol-anandamide {"}hybrids{"} differing in the side chain group. Compounds bearing a 2-methyloctan-2-yl group at position 5 showed a significantly higher affinity for cannabinoid (CB) receptors, in particular when an alkyloxy chain of 7 or 10 carbon atoms was also present at position 1. Derivative 32 was a potent CB 1 and CB 2 ligand, with K i values similar to that of WIN 55-212 and potent antinociceptive activity in vivo. Moreover, derivative 38, although less potent, proved to be the most selective ligand for CB 2 receptor (K i(CB 1)) 1 μM, K i(CB 2)) 35 nM).",

author = "Antonella Brizzi and Vittorio Brizzi and Cascio, {Maria Grazia} and Federico Corelli and Francesca Guida and Alessia Ligresti and Sabatino Maione and Adriano Martinelli and Serena Pasquini and Tiziano Tuccinardi and {Di Marzo}, Vincenzo",

note = "Acknowledgement: The authors from the University of Siena thank the Ministero dell{\textquoteright}Universit{\`a} e della Ricerca (PRIN 2006, Prot. n 2006030948_002) for financial support. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH Grant P41 RR-01081). The authors are grateful to Marco Allar{\`a} for technical assistance with the binding assays.",

year = "2009",

month = apr,

day = "23",

doi = "10.1021/jm8016255",

language = "English",

volume = "52",

pages = "2506--2514",

journal = "Journal of Medicinal Chemistry",

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T1 - New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo

AU - Brizzi, Antonella

AU - Brizzi, Vittorio

AU - Cascio, Maria Grazia

AU - Corelli, Federico

AU - Guida, Francesca

AU - Ligresti, Alessia

AU - Maione, Sabatino

AU - Martinelli, Adriano

AU - Pasquini, Serena

AU - Tuccinardi, Tiziano

AU - Di Marzo, Vincenzo

N1 - Acknowledgement: The authors from the University of Siena thank the Ministero dell’Università e della Ricerca (PRIN 2006, Prot. n 2006030948_002) for financial support. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH Grant P41 RR-01081). The authors are grateful to Marco Allarà for technical assistance with the binding assays.

PY - 2009/4/23

Y1 - 2009/4/23

N2 - Bearing in mind the pharmacophoric requirements of both (-)-trans-Δ 9-tetrahydrocannabinol (THC) and anandamide (AEA), we designed a novel pharmacophore consisting of both a rigid aromatic backbone and a flexible chain with the aim to develop a series of stable and potent ligands of cannabinoid receptors. In this paper we report the synthesis, docking studies, and structure-activity relationships of new resorcinol-anandamide "hybrids" differing in the side chain group. Compounds bearing a 2-methyloctan-2-yl group at position 5 showed a significantly higher affinity for cannabinoid (CB) receptors, in particular when an alkyloxy chain of 7 or 10 carbon atoms was also present at position 1. Derivative 32 was a potent CB 1 and CB 2 ligand, with K i values similar to that of WIN 55-212 and potent antinociceptive activity in vivo. Moreover, derivative 38, although less potent, proved to be the most selective ligand for CB 2 receptor (K i(CB 1)) 1 μM, K i(CB 2)) 35 nM).

AB - Bearing in mind the pharmacophoric requirements of both (-)-trans-Δ 9-tetrahydrocannabinol (THC) and anandamide (AEA), we designed a novel pharmacophore consisting of both a rigid aromatic backbone and a flexible chain with the aim to develop a series of stable and potent ligands of cannabinoid receptors. In this paper we report the synthesis, docking studies, and structure-activity relationships of new resorcinol-anandamide "hybrids" differing in the side chain group. Compounds bearing a 2-methyloctan-2-yl group at position 5 showed a significantly higher affinity for cannabinoid (CB) receptors, in particular when an alkyloxy chain of 7 or 10 carbon atoms was also present at position 1. Derivative 32 was a potent CB 1 and CB 2 ligand, with K i values similar to that of WIN 55-212 and potent antinociceptive activity in vivo. Moreover, derivative 38, although less potent, proved to be the most selective ligand for CB 2 receptor (K i(CB 1)) 1 μM, K i(CB 2)) 35 nM).

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