Synthesis and CB1 receptor activities of dimethylheptyl derivatives of 2-arachidonoyl glycerol (2-AG) and 2-arachidonyl glyceryl ether (2-AGE)

A1 Journal article (refereed)

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Publication Details

List of Authors: Parkkari, Salo, Huttunen, Savinainen, Laitinen, Poso, Nevalainen, Järvinen
Publication year: 2006
Journal: Bioorganic and Medicinal Chemistry
Journal acronym: Bioorg Med Chem
Volume number: 14
Issue number: 8
Start page: 2850
End page: 2858
ISSN: 0968-0896
eISSN: 1464-3391


Results from a factor analysis and activity studies of commercially available endocannabinoid-type compounds set the starting point for the current study where dimethylheptyl (DMH) analogues of two endocannabinoids, 2-arachidonoyl glycerol (2-AG) and 2-arachidonyl glyceryl ether (2-AGE), were synthesized and their ability to activate the CB1 receptors was determined by the [35S]GTPgammaS binding assay using rat cerebellar membranes. The main goal of the study was to examine how the DMH end tail affects the activity properties of 2-AG (1) and its stable ether (2) and urea analogues (5). The importance of the chain length was also explored by synthesizing 2-AG and 2-AGE derivatives (3 and 4) possessing the chain length C21 instead of C22. Replacement of the pentyl end chain with the DMH resulted in distinct potency decrease as compared to the reference compounds. The modification did not have such a strong impact on the efficacy values. In fact, the efficacy of the derivatives of 2-AGE (2 and 4) was comparable or even improved. Introducing a more stable and hydrophilic urea bond led to a dramatic decrease in biological activity.

Last updated on 2020-25-09 at 06:50