Conglomerate and Analgesic Activity of 6-bromo-2-(o-aminophenyl)-3-amino-Quinazolin-4(3H)-one from 6-bromo,2-(o-aminophenyl)-3,1-benzoxazin-4(3H)-one .

: Introduction: Quinazolinone by–product disclosed various curative characteristics such as analgesic, anti-inflammatory and anticancer activities, as well as antimicrobial activity. These heterocycles are beneficial intermediates in organic synthesis. Methods/Experimental: The compound, 6-bromo,2-(o-aminophenyl)-3,1-benzoxazin-4(3H)-one(1) was integrated by dissolving 5-bromo anthranillic acid in 100 ml of pyridine. To this reaction mixture o-amino benzoyl chloride stirring at room temperature for 30 minutes this was refluxed with 75 mL of hydrazine hydrate for 3 hrs at 120-130 0 C. the reaction mixture was allowed to cool to room temperature to give 6-bromo-2-(o-aminophenyl)-3-amino-Quinazolin-4(3H)-one (2). These Compounds were evaluated for their analgesic activity using Acetic acid induced model. Study Design: This study was experimentally design and the analgesic activity was evaluated

This investigation was aimed at synthesis and survey of these compounds for their analgesic activity and to acquire more precise information about the course of reaction.

Chemistry.
The presentation of 2-amino substituent is a successful master plan to improve the chemical solidity of benzoxazinone.Due to the microbicidal and pharmacological activities of 4(3H)quinazolinone derivatives, 2,3-disubstituted derivative of quinazoline-4-one were conglomerated via the interaction of the benzoxazinone derivative with nitrogen nucleophile with the aim of obtaining more accurate information about the course of the reaction and some captivating pharmaceutical compounds.Dissolving 5-bromo anthranillic acid in 100 ml of pyridine in o-amino benzoyl chloride stirring at room temperature for 30 minutes produce the cyclic compound 6-bromo,2-(o-aminophenyl)-3,1-benzoxazin-4(3H)-one (1).The reaction of this compound with 75 mL of hydrazine hydrates for 3 hrs at 120-130 0 C. the reaction mixture was allowed to cool to room temperature to give 6-bromo-2-(o-aminophenyl)-3amino-Quinazolin-4(3H)-one (2).

Experimental
All testing agents and cleaners were acquied from sigma-Aldrich, in Germany.Melting points were resolved on a kofler hot stage apparatus and were uncorrected.IR spectra were recorded on a Buck scientific IR M500 instrument.The 1 H and 13 C NMR spectra were recorded in DMSO-d6 at 400 MHz with HAZ VOLATILE V2.M Chemical shifts Sare reported in ppm relative to tetramethylsilane.Gas chromatography mass spectra were obtained on a Finingan MAT 44S mass spectrophotometer operating at 70eV.Elemental analysis concord favourably with the calculated values.Analytical thin layer chromatography (TLC) was used to praepostor the reactions.

Elemental Analysis
Summary of the structure of the compounds is showned in Table 1.The C and H contents (both theoretically calculated values and actual values) are indicated.

Pharmacological evaluation
Wistar rats (180-230g) of either sex kept in the laboratory animal house of the Faculty of pharmacy, University of Benin, Benin City, Nigeria were used.The animals were maintained under standard environmental conditions and had free access to standard diet and water.Test compounds were orchestrated orally by gavage in 10% olive oil suspensions at different dose levels).Ethical approval was procued from the Animal Use and Ethics committee of the Faculty of Pharmacy, University of Benin, Benin City, Nigeria.

FIGURE 1 :
FIGURE 1: Analgesic Activity of Compound 1 and 2 Against Acetic Acid-Induced Writhing in mice.

Table 1 :
Characterization And Physical Data Of Synthesized Compounds

Table 3 :
1H-NMR Of Synthesized Compounds These compounds synthesized exhibited promising Analgesic activities.The in-vivo analgesic activity of compounds synthesized were determined using carrageenan induced paw edema and the results obtained are summarized in Figure1.Compound 1 has Analgesic activity of 61.33% and 83.18% at 20mg/kg and 40mg/kg dose levels, while Compound 2 has Analgesic activity of 69.49% and 83.18% at 20mg/kg and 40mg/kg dose levels.Compound 2 showed the highest activity at 40mg.kg compared to the other compound 1, and indomethacin a standard Analgesic drug.These compounds synthesized have a higher activity than indomethacin, which is a standard analgesic drug.
compound 2 showed signals at δ24.12, attributed to phenyl group, while the aromatic carbon atoms appeared between δ values 105.64 -160.28, with the carbonyl carbon atom appearing as the highest δ value of 160.28.
1 and 2 have high analgesic activity.Compound 1 has Analgesic activity of 61.33% and 71.14% at 20mg/kg and 40mg/kg dose levels, while Compound 2 has Analgesic activity of 69.49% and 83.18% at 20mg/kg and 40mg/kg dose levels.Compound 2 has a higher Analgesic activity compared to Compound 1 and Indomethacin a standard Analgesic drug.From this result, Compound 2 could be a potential Analgesic and a tool to pharmaceutical drug delivery.