220556-69-4

Basic information

• Product Name: ACEA
• Synonyms: N-(2-CHLOROETHYL)-5Z,8Z,11Z,14Z-EICOSATETRAENAMIDE;ARACHIDONYL-2'-CHLOROETHYLAMIDE;ARACHIDONYL-2-CHLOROETHYLAMIDE;ARACHIDONOYL 2'-CHLOROETHYLAMIDE;ACEA;2'-CHLORO-AEA;ARACHIDONYL-2'-CHLOROETHYLAMIDE HYDRATE;ACEA (ethanol solution)
• CAS NO: 220556-69-4
• Molecular Formula: C22H36ClNO
• Molecular Weight: 365.98
• Product Categories: Cannabinoid receptor;Cannabinoid;Agonist;Fatty Acid Derivatives & Lipids;Glycerols;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 220556-69-4.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 517.9 °C at 760 mmHg
• Flash Point: 267 °C
• Appearance: pale yellow/oil
• Density: 0.954 g/cm³
• Storage Temp.: −20°C
• Solubility: DMSO: soluble
• Water Solubility: DMSO: soluble
• Sensitive: Air Sensitive
• CAS DataBase Reference: ACEA(CAS DataBase Reference)
• NIST Chemistry Reference: ACEA(220556-69-4)
• EPA Substance Registry System: ACEA(220556-69-4)

Safety Data

• WGK Germany: 3
• RTECS: JX3840800
• Hazardous Substances Data: 220556-69-4(Hazardous Substances Data)

Usage

Description

Arachidonoyl 2-chloroethylamide (ACEA) is a potent and selective cannabinoid (CB) receptor 1 agonist with Ki values of 1.4 and >2,000 nM for CB1 and CB2 receptors, respectively. In whole animal experiments, ACEA induces hypothermia in mice with the same efficacy as arachidonoyl ethanolamide (AEA; ), in spite of its higher affinity for the CB1 receptor. These data have been interpreted to indicate that ACEA may be a substrate for fatty acid amide hydrolase (FAAH), and thus only transiently available in whole animal experiments.

Uses

A synthetic agonist of the cannabinoid receptor 1 (CB1R). ACEA is considered to be a selective cannabinoid agonist as it binds primarily to the CB1R and has low affinity to the cannabinoid receptor 2 (CB2R).

Biological Activity

Potent and highly selective CB 1 receptor agonist (K i = 1.4 nM). Displays > 1400-fold selectivity over CB 2 receptors. Active in vivo . Also available as part of the Cannabinoid CB 1 Receptor Tocriset? .

Biochem/physiol Actions

Potent and selective neuronal CB1 cannabinoid receptor agonist.

Enzyme inhibitor

This synthetic CB1 receptor agonist and anandamide (N- arachidonylethanolamide) analogue (FW = 365.99 g/mol; CAS 220556-69-4; Symbol: ACEA) is a selective agonist of cannabinoid receptor-1 (Ki = 1.4 nM) but has low affinity to the cannabinoid receptor 2 (Ki = 3.1 μM). ACEA inhibits forskolin-induced cAMP accumulation in Chinese hamster ovary cells expressing the human CB1 receptor. It also increases the binding of [ 35 S]GTPgS to cerebellar membranes and inhibits electrically evoked contractions of the mouse vas deferens. ACEA produces hypothermia in mice, an effect that is inhibited by co-administration of the CB1 receptor antagonist SR141716A.

Upstream product

• 506-32-1 all cis 5,8,11,14-eicosatetraenoic acid 
• 870-24-6 2-chloroethanamine hydrochloride 
• 57303-04-5 arachidonoyl chloride 

Relevant articles and documents

Cannabimimetic lipid amides as useful medications

Novel analogs of arachidonylethanolamide are presented which have higher affinities for the cannabinoid CB1 and/or CB2 receptor sites. Further, most of the analogs exhibit greater metabolic stability than arachidonylethanolamide. The improved receptor aff

Novel analogues of arachidonylethanolamide (anandamide): Affinities for the CB1 and CB2 cannabinoid receptors and metabolic stability

Several analogues of the endogenous cannabinoid receptor ligand arachidonylethanolamide (anandamide) were synthesized and evaluated in order to study (a) the structural requirements for high-affinity binding to the CB1 and CB2 cannabinoid receptors and (b) their hydrolytic stability toward anandamide amidase. The series reported here was aimed at exploring structure-activity relationships (SAR) primarily with regard to stereoelectronic requirements of ethanolamido headgroup for interaction with the cannabinoid receptor active site. Receptor affinities, reported as K(i) values, were obtained by a standard receptor binding assay using [3H]CP- 55,940 as the radioligand, while stability toward the amidase was evaluated by comparing the K(i) of each analogue in the presence and absence of phenylmethanesulfonyl fluoride (PMSF), a serine protease blocker and inhibitor of anandamide amidase. Introduction of a methyl group in the 1'- and 2'-positions or substitution of the ethanolamido headgroup with a butylamido group gave analogues with vastly improved biochemical stability. This is accomplished in some cases with increased receptor affinity. Conversely, oxazolyl and methyloxazolyl headgroups led to low-affinity analogues. Substitution of the hydroxyl group with electronegative substituents such as fluoro, chloro, allyl, and propargyl groups significantly increased receptor affinity but did not influence the biochemical stability. The 2'-chloro analogue of anandamide was found to have the highest affinity for CB1. Additionally, reversing the positions of the carbonyl and NH in the amido group produces retro-anandamides possessing considerably higher metabolic stability. Replacement of the arachidonyl tail with oleyl or linoleyl results in analogues with low affinities for both receptors. All of the analogues in this study showed high selectivity for the CB1 receptor over the peripheral CB2 receptor. The most potent analogues were tested for their ability to stimulate the binding of [35S]GTPγS to G- proteins and were shown to be potent cannabimimetic agonists. The results are discussed in terms of pharmacophoric features affecting receptor affinity and enzymatic stability.