Abstract

SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF NOVEL BENZOXAZOLE DERIVATIVES AS POTENT HYPNOTIC AGENT

Shruti Dwivedi*, Amrita Singh and Abhinav Prasoon Mishra

ABSTRACT

Insomnia refers the problem with sleep depth or time duration and difficulties during initiation or maintaining sleep. It might be the sole symptom or more commonly it occurs with extra medical or psychological issues including pain and depression. Benzoxazole is a heterocyclic molecule; benzene-fused (oxazole ring) its chemical name is 1-Oxa-3-aza-1H-indene. In 1887, Hantzsch was the first to present this chemical. This study was focused on the synthesis and hypnotic evaluation of novel benzoxazole derivatives as potent hypnotic agent. The 2-aminophenol in methanolic solution was reacted with potassium hydroxide and carbon-di-sulfide to produce benzo[d]oxazole-2-thiol (II). To make 2-(((1H-benzimidazol-2-yl) methyl)thio)benzoxazole, a combination of I and II was mixed in the presence of triethylamine. Derivatives were characterized through melting point, TLC, infrared and NMR spectroscopy. Rats (both sexes) weighing between 120 and 150g provided by the Animal House at the Advance Institute of Biotech & Paramedical Sciences in Kanpur. The rats were divided in 4 groups i.e., group 1 administered vehicle daily, group 2 administered Diazepam (4mg/kg) orally, group 3 administered all the novel derivatives (100mg/kg) orally, and group 4 administered all the novel derivatives (200mg/kg) orally. The hypnotic effect of synthesized derivatives by following screening models i.e., thiopental sod. induced sleeping and motor co-ordination test. For benzoxazole derivative, the melting point was determined as 209ºC, 223ºC, 235ºC, 190ºC, 239ºC and 220ºC for compounds C1, C2, C3, C4, C5 and C6, respectively. C2 and C4 were demonstrated for its highest % yield as 71.24% and 71.11%. Lowest % yield was seen in C3 as 63.19%. Whereas, the benzoxazole derivatives (100mg/kg) exhibited the motion as 98± 2.21***sec, 102± 2.27***sec, 88± 2.36***sec and 92± 2.53***sec in C1, C2, C3 and C4, respectively. Among the several benzoxazole derivatives, the results show that C4 and C5 are the most effective in treating insomnia and its symptoms. It could also be improved to the point where manufacturing it would be economically viable, given its potential value. Insomnia and stress are two of the most common causes of mental incapacity, and they may have economic and pharmaceutical effects on people's behavior.

Keywords: Benzoxazole, Heterocycle compounds, Insomnia, hypnotic, NMR.