197587-19-2Relevant academic research and scientific papers
Synthesis of covalent probes for the radiolabeling of the cannabinoid receptor
Chu, Chester,Ramamurthy, Arun,Makriyannis, Alexandros,Tius, Marcus A.
, p. 55 - 61 (2003)
The main psychoactive constituent of marijuana, (-)-Α9-tetrahydrocannabinol, produces most of its physiological effects by interacting with the CB1 cannabinoid receptor, a membrane protein belonging to the large superfamily of G-protein coupled receptors. The 3-D structure of the receptor binding site is of value in the design of novel medications for a variety of therapeutic indications. To obtain information on the amino acid residues associated with this binding site, we have designed and synthesized a cannabinergic CB1 ligand prototype carrying an electrophilic isothiocyanato group capable of reacting covalently with amino acid residues bearing thiol or unprotonated amino groups. The ligand also incorporates an iodide atom, which can serve as a high-activity radiolabel. The key step in our synthesis involves a rapid intramolecular Diels-Alder reaction of a transiently formed o-quinone methide, which proceeds stereospecifically with the formation of the tricyclic cannabinoid template. Introduction of the iodo group is the last step in the sequence and is compatible with the use of 125I-radiolabel.
Highly Selective, Amine-Derived Cannabinoid Receptor 2 Probes
Carreira, Erick M.,Grether, Uwe,Guba, Wolfgang,Osterwald, Anja,Sarott, Roman C.,Ullmer, Christoph,Westphal, Matthias V.,Zirwes, Elisabeth A.
supporting information, p. 1380 - 1387 (2020/02/05)
The endocannabinoid (eCB) system is implied in various human diseases ranging from central nervous system to autoimmune disorders. Cannabinoid receptor 2 (CB2R) is an integral component of the eCB system. Yet, the downstream effects elicited by this G protein-coupled receptor upon binding of endogenous or synthetic ligands are insufficiently understood—likely due to the limited arsenal of reliable biological and chemical tools. Herein, we report the design and synthesis of CB2R-selective cannabinoids along with their in vitro pharmacological characterization (binding and functional studies). They combine structural features of HU-308 and AM841 to give chimeric ligands that emerge as potent CB2R agonists with high selectivity over the closely related cannabinoid receptor 1 (CB1R). The synthesis work includes convenient preparation of substituted resorcinols often found in cannabinoids. The utility of the synthetic cannabinoids in this study is showcased by preparation of the most selective high-affinity fluorescent probe for CB2R to date.
Synthesis of a bifunctional cannabinoid ligand
Tius, Marcus A.,Busch-Petersen, Jakob,Marris, Andrew R.
, p. 1867 - 1868 (2007/10/03)
A novel bifunctional classical-nonclassical hybrid cannabinoid has been prepared expeditiously through the Diels-Alder reaction of an ortho-quinomethane.
