Research Article A NOVEL APPROACH TOWARDS DEVELOPMENT OF QUINAZOLINE DERIVATIVES IN PAIN MANAGEMENT NIRAJ KUMAR SINHA*, ALPANA J ASNANI, BHUSHAN R DRAVYAKAR J. L. Chaturvedi College of Pharmacy, M.I.D.C., Hingna Road, Nagpur-india. Email : niraj.sinha101@gmail.com Received: 10 June 2013, Revised and Accepted: 5 July 2013 ABSTRACT Objective: To synthesize and evaluate the analgesic and anti-inflammatory activities of pyrazoline bearing 4(3H)-quinazolinone derivatives. Methods: Synthesis of Chalcone (3a-3j) involves the Claisen-Schmidt condensation of equimolar quantities of substituted acetophenone with aromatic aldehyde in the presence of aqueous alkali (10%). Comp. (3a-3j) undergoes cyloaddition reaction with semicarbazide HCl in the presence of suitable solvent to yield comp. (4a-4j). It undergoes addition cyclization reaction with anthranillic acid to yield final comp. (6a-6j). Acute toxicity study of synthesized compound was found according to OECD guidelines 423. The test compound do not showed any toxicity up to 200mg/kg dose. Mortality was not observed during the course of study. The analgesic and anti-inflammatory activity of all synthesized compounds were carried by using hot plate method and Carrageenan induced Rat Paw Edema Method respectively. Results: All compounds synthesized are obtained in crystalline form with good practical yield. The purity and homogeneity of compounds synthesized were determined by sharp melting points and TLC method. The chemical structures were confirmed by FTIR, 1 HNMR, and Mass spectrum. Conclusion: The synthesized compound 6b, 6d, 6e, 6i and 6j showed good analgesic and anti-inflammatory activities whereas others showed significant activities. Keywords: Quinazoline, pyrazole, analgesic and anti-inflammatory activity. INTRODUCTION Quinazoline is a compound made up of two fused six-membered simple aromatic rings, structure compound containing benzene fused to pyrimidine. Medicinally it has been used in various areas as an analgesic and anti-inflammatory [1-4], antihypertensive [5-6], antimicrobial [7-9], antibacterial [10], anticonvulsant [11-13], anticancer [14-15], antimalarial [16] and antidepressant activities [17]. Pyrazole derivatives also exhibit some similar set of activities such as antimicrobial [18] and analgesic, anti-inflammatory [19]. It has been reported that substitution pattern by different aryl or heteroaryl moieties at 2/3 position of quinazoline nucleus markedly influences the anti-inflammatory activity [20]. On the other hand, sulphonamides [21], imidazoles [22], pyrazoles [23] are other important pharmacodynamic heterocyclic nuclei which when incorporated into different heterocyclic templates, have been reported to possess potent anti-inflammatory activity. Based on the above observations and in continuation of our anti-inflammatory and analgesic drug research program, it was of interest to adjoin the above said moiety to obtain expectedly more potent compounds with lesser side effects. The structures were confirmed by IR, 1 HNMR, mass spectra and elemental analysis. These compounds were screened for analgesic and anti-inflammatory activity using hot plate method and rat paw edema method respectively. MATERIALS AND METHODS The chemicals used in the present work were AR grade and LR grade, purchased from Loba, Merck and Fisher scientific fine chemicals. The synthesized compounds were scaled for yield and purified by recrystallization with suitable solvent system. The melting point of the synthesized compounds were determined in open capillary using LABHOSP melting point apparatus and recorded in o C without correction. Thin layer chromatography was performed on silica gel G plates using Hexane: Ethyl acetate (7:3) solvent system. The structures were further confirmed by elemental (CHN) and spectral analysis like Infrared spectroscopy, Nuclear magnetic resonance spectroscopy and mass spectroscopy. General Procedure The title compounds were prepared in following steps: Synthesis of 1, 3-Diphenyl prop-2-en-1-one derivatives (Chalcone) (3a-3j). A mixture of benzaldehyde (0.01 mol) and acetophenone (0.01 mol) was dissolved in 10 ml rectified spirit in a 250 ml round‐bottomed flask equipped with a magnetic stirrer. Then added 10 ml (10%) NaOH solution drop wise to the reaction mixture on vigorous stirring for 30 minutes when solution became turbid, the reaction temperature was maintained between 20‐25˚ C using a cold water bath on the magnetic stirrer. After vigorous stirring for 4‐5 hr the reaction mixture was neutralized by 0.1N HCl whereby the precipitation occurred. The crude chalcone was filterd, dried in air and recrystallized by rectified spirit. By adopting the above procedures comp. (3b-3j) were synthesized using different benzaldehydes and acetophenones in equimolar concentration. Synthesis of 3,5-Diaryl-4,5-dihydropyrazole-1-carboxamide derivatives (4a-4j). A mixture of the respective chalcone derivatives (3a) (0.01 mol), semicarbazide HCl (0.01 mol) and NaOH (0.5 g, 0.0125 mol) was heated under reflux in absolute ethanol (25 ml) for 7-8 hrs. The reaction mixture was cooled and poured into ice cold water. The solid separated was filtered, dried and crystallized from the ethanol. By using above procedure comp. (4b-4j) were synthesized. Synthesis of 2-(3, 5-Diaryl-4,5-dihydro-1H-pyrazol-1-yl) quinazoline-4-one (6a-6j). A mixture of anthranilic acid (0.01 mol) and Comp. 4a (0.01 mol) was heated on an oil bath at 120 -130 0 C for 2-3 hr. Subsequently, the melt was allowed to cool for 30 min at room temperature. During this period, the melted mass solidified. It was treated with an aqueous solution of sodium bicarbonate (10%) in order to dissolve any unreacted acid into the cyclised product. An additional quantity of sodium bicarbonate solution was added to ensure the complete dissolution of the acid (until there was no effervescence of carbon dioxide). The solid was filtered off and washed with water in order to remove any inorganic materials. It was dried under vacuum over night and recrystallized from ethanol as white crystalline mass. Using the above procedure, nine different derivatives comp. (6b-6j) were synthesized. Vol 6, Suppl 3, 2013 ISSN - 0974-2441