Evaluation of Anti-Inflammatory and Analgesic Activity of Novel Pyrazole Derivatives

A new series of novel derivatives of pyrazole were synthesized. These derivatives were identified on the basis of melting point range, Rf values, IR and 1H NMR spectral analysis. The derivatives were screened for antiinflammatory and analgesic activities. The derivatives exhibited significant to moderate anti-inflammatory and analgesic activities. Cite this article as: Abhay Kumar Verma, Alex Martin, Arun Kumar Singh (Sr.). Evaluation of Anti-Inflammatory and Analgesic Activity of Novel Pyrazole Derivatives. Asian Journal of Biomedical and Pharmaceutical Sciences; 04 (37); 2014, 21-24. Abhay Kumar Verma et al: Asian Journal of Biomedical and Pharmaceutical Sciences; 4(37) 2014, 21-25. © Asian Journal of Biomedical and Pharmaceutical Sciences, all rights reserved. Volume 4, Issue 37, 2014. 22 INTRODUCTION Nitrogen containing heterocyclic compounds are synthetically the challenging models for a number of therapeutically significant products. Azoles occupy a domain of interest in natural and synthetic chemistry. Diazoles are the central building blocks for synthesizing compound libraries in pharmaceutical and agrochemical industries. One such class of compounds includes Pyrazole. Pyrazole refers to the simple doubly unsaturated compound containing two nitrogen (in neighbouring position) and three carbon atoms in the ring. The pyrazole nucleus is common in a number of biologically active molecules exhibiting antibacterial [1-2], antitubercular [3], anti depressant [4], antiinflammatory [5-6], analgesic [7], anticancer [8-9], antioxidant [10-11] etc. activities. Research in this area is still unexplored, therefore the present study is directed towards the synthesis of novel derivatives of pyrazole with good yield and enhance antiinflammatory and analgesic activities. MATERIALS AND METHODS All the chemicals procured from CHEMCO Labs, NICE chemicals. The melting points were determined in open glass capillaries and were uncorrected. Thin Layer Chromatography using silica gel G (E. Merck) plates were used to access the reaction and purity of synthesized compounds. The IR spectra were recorded on Shimadzu FTIR system in KBr pellets and noted the absorption levels (cm-1) were listed. 1H NMR spectra were run on Bruker DPX 400 FTNMR in DMSO-d6 as solvent and TMS as an internal standard. The Mass spectra were recorded on JEOL JMS600H mass spectrometer. Step1: Synthesis of Ethyl-4-chlorobenzoate P-chloro benzoic acid (30g) in ethanol was added with 150ml conc. sulphuric acid at 0.5 0C over a period of 30 min and refluxed for 2 hrs on a water bath. The reaction mixture was poured in to ice-cold water. The solid thus obtained was filtered, washed and dried. The dried product was recrystallised from ethanol to white needle shaped crystals.Yield:95.5% w/w. Step2: Synthesis of 4-chloro benzohydrazide The mixture of 0.167 mol (29g) of substituted esters and 0.167 mol(5g)of hydrazine was warmed with 60ml of ethanol and few drops of glacial acetic acid. The reaction mixture was cooled and filtered. The solid thus obtained was washed with dil. HCl followed by about 12ml of cold rectified spirit. The dried product was recrystallised from ethanol to white needle shaped crystals of pure 4-chloro benzohydrazide.Yield:93% w/w. Step3: Synthesis of (E)-4-chloro-N'-(1-(4substituted phenyl)ethylidene) benzohydrazide 0.01mol of substituted acetophenone was added to the mixture containing 0.01mol of 4chlorobenzohydrazide in 30ml of ethanol and few drops of glacial acetic acid. The reaction mixture was refluxed for 1 hr and then cooled in ice-bath. The product separated on cooling was filtered, dried and recrystallised from ethanol to white needle like crystals. (PZ1-PZ5) Step 4 : Synthesis of 1-(4-chlorobenzoyl)-3-(4 substituted phenyl)-1H-pyrazole-4-carbaldehyde Cyclisation: The substituted hydrazone (0.005mol) was added in to the mixture of Vilsmeier-Haack (DMF&POCl3) reagent, prepared by drop wise addition of phosphorous oxy chloride 140ml (0.015mol) to an ice-cold solution of N,N-dimethyl formamide 20ml.The reaction mixture was refluxed for 2 hrs, then poured in to ice-cold water and neutralized using an excess of sodium bicarbonate solution. The product was washed with water and recrystallised from ethanol. (PZ1-PZ5).