α-Methylated derivatives of 2-arachidonoyl glycerol:: Synthesis, CB1 receptor activity, and enzymatic stability

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:16

Article

Parkkari, T ; Myllymäki, M ; Savinainen, JR ; Saario, SM ; Castillo-Meléndez, JA ; Laitinen, JT ; Nevalainen, T ; Koskinen, AMP ; Järvinen, T

关键词: cannabinoid;    CB1 receptor;    2-AG;    enzymatic stability;    stereoselective synthesis;   

DOI  :  10.1016/j.bmcl.2006.01.101

来源: Elsevier

【 摘 要 】

alpha-Methylated analogues of the endogenous cannabinoid, 2-arachidonoyl glycerol (2-AG), were synthesized aiming to the improved enzymatic stability of 2-AG. In addition, the CB1 activity properties of fluoro derivatives of 2-AG were studied. The CB1 receptor activity was determined by the [S-35]GTP gamma S binding assay, and the enzymatic stability of alpha-methylated analogues was determined in rat cerebellar membranes. The results indicate that even if the alpha-methylated 2-AG derivatives are slightly weaker CB1 receptor agonists than 2-AG, they are clearly more stable than 2-AG. In addition, the results showed that the replacement of the hydroxyl group(s) of 2-AG by fluorine does not improve the CB1 activity of 2-AG. (C) 2006 Elsevier Ltd. All rights reserved.

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