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

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

Uses

Used in Pharmaceutical Industry:
ACEA is used as a synthetic agonist for the cannabinoid receptor 1 (CB1R) for its potential therapeutic applications in various medical conditions. Its high selectivity for CB1R makes it a valuable compound for research and development in the pharmaceutical industry.
Used in Research and Development:
ACEA is used as a research tool to study the effects and mechanisms of action of cannabinoid receptor 1 agonists. Its selective binding to CB1R allows scientists to investigate the role of this receptor in various physiological processes and potential therapeutic applications.
Used in Drug Design and Development:
ACEA's potent and selective agonist activity towards CB1R makes it a useful starting point for the design and development of new drugs targeting the endocannabinoid system. Its properties can be leveraged to create more effective and targeted therapies for a range of medical conditions.
Used in Neurological and Pain Research:
ACEA's ability to induce hypothermia in mice and its interaction with the CB1 receptor make it a valuable compound for studying the role of the endocannabinoid system in neurological disorders and pain management. This can lead to the development of new treatments for conditions such as multiple sclerosis, epilepsy, and chronic pain.

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

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

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

Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1)

Two subtypes of the cannabinoid receptor (CB1 and CB2) are expressed in mammalian tissues. Although selective antagonists are available for each of the subtypes, most of the available cannabinoid agonists bind to both CB1 and CB2 with similar affinities. We have synthesized two analogs of N- arachidonylethanolamine (AEA), arachidonylcyclopropylamide (ACPA) and arachidonyl-2-chloroethylamide (ACEA), that bind to the CB1 receptor with very high affinity (K1 values of 2.2 ± 0.4 nM and 1.4 ± 0.3 nM, respectively) and to the CB2 receptor with low affinity (K, values of 0.7 ± 0.01 μM and 3.1 ± 1.0 μM, respectively). Both ACPA and ACEA have the characteristics of agonists at the CB1 receptor; both inhibit forskolin- induced accumulation of cAMP in Chinese hamster ovary cells expressing the human CB1 receptor, and both analogs increase the binding of [35S]GTPγS to cerebellar membranes and inhibit electrically evoked contractions of the mouse vas deferens. ACPA and ACEA produce hypothermia in mice; and this effect is inhibited by coadministration of the CB1 receptor antagonist SR141716A. Therefore, ACPA and ACEA are high-affinity agonists of the CB1 receptor but do not bind the CB2 receptor, suggesting that structural analogs of AEA can be designed with considerable selectivity for the CB1 receptor over the CB2 receptor.

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.