Synthesis and characterizations of novel quinoline derivatives having mixed ligand activities at the κ and μ receptors: Potential therapeutic efficacy against morphine dependence

Based on an established 3D pharmacophore, a series of quinoline derivatives were synthesized. The opioidergic properties of these compounds were determined by a competitive binding assay using 125I-Dynorphine, 3H-DAMGO and 125I-DADLE for κ, μ, and δ receptors, respectively. Results showed varying degree of activities of the compounds to κ and μ opioid receptors with negligible interactions at the δ receptor. The compound, S4 was the most successful in inhibiting the two most prominent quantitative features of naloxone precipitated withdrawal symptoms - stereotyped jumping and body weight loss. Determination of IC50 of S4 revealed a greater affinity towards μ compared to κ receptor. In conclusion, quinoline derivatives of S4 like structure offer potential tool for treatment of narcotic addictions.

Based on an established 3D pharmacophore, a series of quinoline derivatives were synthesized and their binding activities to opioid receptors as well as pharmacotherapeutic ability in controlling the naloxone precipitated withdrawal in morphine dependent mice were investigated, which revealed that quinoline derivatives might be potential tool for treatment of narcotic addictions.Figure optionsDownload as PowerPoint slide