Discovery of EST73502, a Dual 娓?Opioid Receptor Agonist and 锜?sub>1 Receptor Antagonist Clinical Candidate for the Treatment of Pain was written by Garcia, Monica;Virgili, Marina;Alonso, Monica;Alegret, Carles;Farran, Joan;Fernandez, Begona;Bordas, Magda;Pascual, Rosalia;Burgueno, Javier;Vidal-Torres, Alba;Fernandez de Henestrosa, Antonio R.;Ayet, Eva;Merlos, Manuel;Vela, Jose Miguel;Plata-Salaman, Carlos R.;Almansa, Carmen. And the article was included in Journal of Medicinal Chemistry in 2020.Formula: C7H9Br2N This article mentions the following:
The synthesis and pharmacol. activity of a new series of 4-alkyl-1-oxa-4,9-diazaspiro[5.5]undecane derivatives as potent dual ligands for the 锜?sub>1 receptor (锜?sub>1R) and the 娓?opioid receptor (MOR) are reported. A lead optimization program over the initial 4-aryl analogs provided 4-alkyl derivatives with the desired functionality and good selectivity and ADME profiles. Compound I (EST73502) showed MOR agonism and 锜?sub>1R antagonism and a potent analgesic activity, comparable to the MOR agonist oxycodone in animal models of acute and chronic pain after single and repeated administration. Contrary to oxycodone, I produces analgesic activity with reduced opioid-induced relevant adverse events, like intestinal transit inhibition and naloxone-precipitated behavioral signs of opiate withdrawal. These results provide evidence that dual MOR agonism and 锜?sub>1R antagonism may be a useful strategy for obtaining potent and safer analgesics and were the basis for the selection of I as a clin. candidate for the treatment of pain. In the experiment, the researchers used many compounds, for example, 2-(2-Bromoethyl)pyridine hydrobromide (cas: 72996-65-7Formula: C7H9Br2N).
2-(2-Bromoethyl)pyridine hydrobromide (cas: 72996-65-7) belongs to pyridine derivatives. Pyridine’s the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.Formula: C7H9Br2N