Development of novel tail-modified anandamide analogs

Abstract

To explore the hydrophobic groove subsite within the CB1 cannabinoid receptor we have designed and synthesized a group of tail-substituted anandamide analogs. Our design involves the introduction of aryl or heterocyclic ring as terminal substituents that are connected to the last cis-arachidonyl double bond through aliphatic chains of variable lengths. Our results indicate that there are strict stereochemical requirements for the interaction of such analogs with the CB1 receptor. The optimal pharmacophore includes the phenyl, p-substituted phenyl or 3-furyl substitutents attached to the cis-double bond through a four methylene chain.

Application of chemoenzymatic hydrolysis in the synthesis of 2-monoacylglycerols

“…An excess of fatty acid is not required for this method which is important when the preparation of the modified fatty acid involves laborious multistep-synthesis. 38–40 This will further enhance the study of structure activity relationships of these biologically important lipid signaling molecules.…”

Evaluation of endogenous fatty acid amides and their synthetic analogues as potential anti-inflammatory leads

“…Based on previous studies on the SAR of bioactive fatty acid amides, it was suggested that both fatty acid component and amine headgroup of the molecule are important for their bioactivity. [19][20][21][22][23] Therefore, each fatty acid component was incorporated with different amine headgroups.…”

“…Inhibitory effects of selected fatty acid amides(2,6,10, 14,18,21,22,24,28, 37, 45, 53, 62, 69, and 77) on the production of NO in LPS-activated RAW264.7 cells. The RAW264.7 cells (1.5 Â 10 5 cells/mL) were stimulated with LPS (1 lg/mL) alone or with test samples at concentrations of 3.125, 6.25, 12.5, and 25 lM for 24 h (BL, blank).…”

Síntese de novas amidas graxas a partir da aminólise de ésteres metílicos

“…Neste trabalho, descreveu-se a síntese de novas amidas graxas com base na similaridade estrutural das amidas já descritas na literatura como, por exemplo, a palmitoiletanolamida (1), 41 anandamida (2), 42 cis-oleamida (3), 43 oleiletanolamida (4) 44 e macamida (5) 10 (Figura 1). A inovação ocorreu devido à presença dos diferentes substituintes ligados ao átomo de nitrogênio e a sua combinação com as cadeias graxas provenientes dos ácidos graxos comerciais, palmítico (6a), esteárico (6b) e oleico (6c) e do óleo de mamona (ricinus communis).…”