Novel 5-susituated analogues of 4H-3-(2-phenoxy)phenyl–1,2,4-triazole derivatives as agonists of benzodiazepine receptors with anxiolytic effect

6^th World Congress on Medicinal Chemistry and Drug Design

June 07-08, 2017 Milan, Italy

Mehrdad Faizi, Aliasghar Peyvandi and Sayyed Abbas Tabatabai

Shahid Beheshti University of Medical Sciences, Iran

Posters & Accepted Abstracts: Med Chem (Los Angeles)

Abstract :

Benzodiazepines are important medicine for treatment and control of a series of disorders including anxiety, insomnia, muscular spasm, and epilepsy. However, they have some unwanted effects such as negative effects on memory and drug dependence. In a search for new active compounds a series of novel non-rigid benzodiazepine ligands, 5-substituted analogues of 4H-3-(2-phenoxy) phenyl-1,2,4-triazole and its chlorinated derivatives were synthesized. The goal is having new ligands with a potential clinical use and less unwanted effects. The novel compounds had several substituents including NH2, SH, S-Methyl groups on position 5 of the 1,2,4-triazole ring. The anxiolytic effects of the novel compounds and diazepam were assessed by elevated plus maze in male NMRI mice. The ED50 was defined as the dose of drug leading to a 100% prolongation in mean duration of staying on open arm of the maze when compared to the control group. Compound with amino substituent at position 5 of the 1,2,4-triazole ring and chloro substituents on position 2 of phenoxy group and position 4 of phenyl ring were the most potent compound in the novel compounds (ED50 of 7.6 mg/kg with 95% confidence interval of 5.5-10.3 mg/kg). These findings are in agreement with structureactivity relationship studies of ligands of benzodiazepine receptors. Flumazenil, a selective antagonist of benzodiazepine receptors, was able to reduce the anxiolytic effect of the compounds, which confirms that the anxiolytic effects were seen are results of the interaction of the novel compounds and benzodiazepine receptors.

Biography :

Email: m.faizi@sbmu.ac.ir