157182-50-8

Usage

Biological Activity

s-1 methanandamide is a cb1 receptor ligand.the cannabinoid receptor type 1 (cb1), is a g protein-coupled cannabinoid receptor located mainly in the central and peripheral nervous system. cb1 is also expressed in several cells relating to metabolism, such as muscle cells, fat cells, liver cells, and the digestive tract. the cb1 receptor has been involved in the maintenance of homeostasis in health and disease, preventing the development of excessive neuronal activity, reducing pain and other inflammatory symptoms. enhanced receptor expression has been identified in human hepatocellular carcinoma tumor samples and human prostate cancer cells [2].s-1 methanandamide was a less potent than the c-1 (r) methyl isomer when binding with cb1 receptor. s-1 methanandamide inhibited electrically evoked contractions in isolated mouse vasa deferentia with an ic50 value of 230 nm. the binding affinity of s-1 methanandamide for cb1 receptors was less than that of aea, with a ki of 175 nm for the displacement of radiolabeled cp 55,940 [1].

Upstream product

• 35320-23-1 (R)-2-aminopropan-1-ol 
• 57303-04-5 arachidonoyl chloride 
• 506-32-1 all cis 5,8,11,14-eicosatetraenoic acid 
• 2749-11-3 (S)-Alaninol 
• 69287-38-3 5,8,11,14-eicosatetraenoic acid methyl ester 
• 6168-72-5 2-Amino-1-propanol 
• 95285-77-1 ethyl arachidonate 

Relevant academic research and scientific papers

Pharmacological and behavioral evaluation of alkylated anandamide analogs

Anandamide (arachidonylethanolamide), isolated from porcine brain, has been shown to bind to the cannabinoid receptor and also to produce cannabimimetic activity in pharmacological assays. This study examined structure-activity relationships in alkylated anandamide analogs. The analogs were evaluated for their ability to displace [3H]CP-55,940 in a filtration binding assay using rat brain membranes in the presence and absence of the enzyme inhibitor phenylmethylsulfonyl fluoride (PMSF). Behavioral activity was assessed by the ability of the analogs to produce hypomotility and antinociception. Methylations at carbons 2 and 1' produced compounds stable in the absence of PMSF with similar affinities and behavioral activity as anandamide. Addition of larger alkyl groups at these positions or nitrogen methylation reduced receptor affinity and behavioral potency. These results indicate that methylations at specific carbons of anandamide confer stability in vitro.

Improved enzymatic procedure for the synthesis of anandamide and N-fatty acylalkanolamine analogues: A combination strategy to antitumor activity

Twenty N-fatty acylamines from linolenic and arachidonic acids, fifteen of them new compounds, were obtained through Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields and with high chemoselectivity. The optimal reaction conditions were achieved by studying the reaction parameters (temperature, E/S ratio, alcohol and alkanolamine/fatty acid ratio, time, solvent, free-solvent system, etc.). To identify ideal enzymatic methods for generating the alkanolamides we evaluated enzyme performance in three procedures: i) aminolysis of ethyl ester, ii) direct condensation between the fatty acid and the alkanolamine, and iii) a one-pot/two-step conversion of fatty acids into alkanolamides via in situ formation of the ethyl ester and subsequent aminolysis by the alkanolamine. The advantages noted with the enzymatic methodology, such as mild reaction conditions and low environmental impact, underscore biocatalysis as a convenient way to prepare the reported compounds. The cytotoxic activities of all compounds and mixtures of anandamide and its analogues were evaluated in rat glioma C6 cells. These studies reveal that some anandamide analogues enhance the antitumor effects of anandamide, suggesting their possible application as therapeutic tools in cancer treatment. Twenty N-fatty acylamines from linolenic and arachidonic acids were obtained by one-pot/two-step Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields with high chemoselectivity. Cytotoxicity assays using rat glioma C6 cells revealed that some analogues enhanced the antitumor effects of anandamide (AEA), suggesting possible anticancer applications.

Enzymatic synthesis of N-acylethanolamines: Direct method for the aminolysis of esters

Immobilized Candida antarctica (Novozyme 435) catalyzed synthesis of N-acylethanolamines is described. Treatment of methyl esters with lipase and amines yielded the desired amides within 2-24 h with yields ranging from 41% to 98%.

Anandamide prodrugs: 1. Water-soluble phosphate esters of arachidonylethanolamide and R-methanandamide

Phosphate esters of arachidonylethanolamide (AEA) and R-methanandamide were synthesized and evaluated as water-soluble prodrugs. Various physicochemical properties (pKa, partition coefficient, aqueous solubility) were determined for the synthesized phosphate esters. The chemical stability of phosphate esters was determined at pH 7.4. In vitro enzymatic hydrolysis rates were determined in 10% liver homogenate, and in a pure enzyme-containing (alkaline phosphatase) solution at pH 7.4. The intraocular pressure (IOP) lowering properties of R-methanandamide phosphate ester were tested on normotensive rabbits. The phosphate promoiety increased the aqueous solubility of the parent compounds by more than 16 500-fold at pH 7.4. Phosphate esters were stable in buffer solutions, but rapidly hydrolyzed to their parent compounds in alkaline phosphatase solution (t1/21/2=8-9 min). The phosphate ester of R-methanandamide reduced IOP in rabbits. These results indicate that the phosphate esters of AEA and R-methanandamide are useful water-soluble prodrugs.

(R)-methanandamide: A chiral novel anandamide possessing higher potency and metabolic stability

Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas deferens. The lead analog was also tested for its potency in vivo. Of the analogs tested, (R)-(+)-arachidonyl-1'-hydroxy- 2'-propylamide [(R)-methanandamide] exhibited the highest affinity for the cannabinoid receptor with a K(i) of 20 ± 1.6 nM, 4-fold lower than that of anandamide (K(i) = 78 ± 2 nM). Moreover, determination of the cannabinoid binding affinity in the presence and absence of the protease inhibitor phenylmethanesulfonyl fluoride (PMSF) revealed that (R)-methanandamide possesses a remarkable stability to aminopeptidase hydrolysis. Pharmacological studies on mouse isolated vasa deferentia demonstrated that all four analogs produce concentration-related inhibition of the twitch response and the order of potency is the same as the rank order of the affinities of these agonists for cannabinoid binding sites. Furthermore, experiments with mice have demonstrated that (R)-methanandamide also possesses cannabimimetric properties in vivo, as established by the four tests of hypothermia, hypokinesia, ring immobility, and antinociception.