Chemical Characterization and in vitro Metabolism of a Novel Class of Delta Opioid Receptor Agonists, Analogs of SNC‐80. Issue 7 (18th February 2019)

• Record Type: Journal Article
• Authors: Usai, Elisabetta Maria; Manca, Ilaria; Pettinau, Francesca; Mastino, Antonio; Pittau, Barbara
• Is Part Of: ChemistrySelect. Volume 4:Issue 7(2019)
• Page Start: 2109
• Page End: 2115
• Publication Date: 2019-02-18
• Subjects: Diazatricyclodecane derivatives -- In vitro metabolism -- Molecular characterization -- Opioids -- Stereoisomers; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201803906
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: The diazatricyclodecane derivatives belong to a novel class of δ opioid receptor agonists, conformationally restricted analogs of SNC‐80. To support further investigation on the potential use of this class of δ opioid receptor agonists in humans, synthesis and chemical characterization of three tricyclic compounds of this class, designated as3–4 ‐5, was carried out. Moreover, drug metabolism of the same compounds was investigated using human liver microsomes. Being drug candidates chiral compounds, they were also evaluated in terms of stereoisomers presence in the drug substances. Pharmacokinetic profiles and kinetic parameters of compound3 and compound4 and Michaelis parameters of compound3 were determined. Remaining percentages of the parent drug versus time were analyzed. Results indicated that the examined derivatives display good in vitro metabolic stability. Abstract : Diazatricyclodecane derivatives belong to a novel class of δ opioid (DOP) receptor agonists. In order to support further investigation on the potential use of this class of DOP receptor agonists in humans, we performed a series of studies to increase the knowledge about this class of molecules in terms of drug substance characterization and metabolic behavior. GOAL: to obtain more information about diazatricyclodecane derivatives in terms of structure, reactivity and chemical/metabolic stability.