Pratik Khanal, Arun Kumar, Neha Srivastava, Bhumika Yogi, Anshuman Sinha, Kumar Gupta Sujeet
Department of Pharmaceutical Chemistry, Hygia Institute of Pharmaceutical Education and Research, Lucknow-206020, India.
Department of Pharmacology, Hygia Institute of Pharmaceutical Education and Research, Lucknow-206020, India.
Antiinflamm Antiallergy Agents Med Chem. 2018;17(1):32-38. doi: 10.2174/1871523017666180411155240.
Recently, pyrazole derivatives have shown significant antiinflammatory activity. Non-steroidal anti-inflammatory drugs have some side effects, mainly gastric irritation and gastric ulceration during the treatment of inflammation. So the current study deals with the synthesis and pharmacological evaluation of a series of novel pyrazole derivatives as anti-inflammatory agents.
A series of novel ethyl 5-(substituted)-1H-pyrazole-3-carboxylate (2a-j) were synthesized and evaluated for anti-inflammatory activity using carrageenan-induced inflammation in rat paw edema model. In the first step, diethyl oxalate react with acetophenone derivatives in presense of sodium ethoxide to form substituted ethyl-2,4-dioxo-4- phenyl butanoate derivatives as intermediate (1a-j). Further the suspension was prepared from dioxo-esters with hydrazine hydrate in glacial acetic acid yielded novel ethyl 5- (substituted)-1H-pyrazole-3-carboxylate (2a-j) derivatives. The structure of the final analogues (2a-j) has been confirmed on the basis of elemental analysis, IR, 1 H NMR and mass spectra.
All the values of elemental analysis, FTIR, 1H NMR, and mass spectra were found to be prominent. The anti-inflammatory activity test revealed that Ethyl 5-(3,4- dimethoxyphenyl)-1H-pyrazole-3-carboxylate (2f) and ethyl 5-(2,3-dimethoxyphenyl)-1Hpyrazole- 3-carboxylate (2e) exhibited significant anti-inflammatory activity as compared to control group.
The results of the current study indicate that the substitution at pyrazole scaffold could improve anti-inflammatory activity.
最近，吡唑衍生物已显示出显著的抗炎活性。非甾体抗炎药有一些副作用，主要是在炎症治疗期间引起胃刺激和胃溃疡。因此，本研究涉及一系列新型吡唑衍生物作为抗炎剂的合成及药理评价。
合成了一系列新型5-（取代基）-1H-吡唑-3-羧酸乙酯（2a-j），并利用角叉菜胶诱导的大鼠足肿胀模型评价其抗炎活性。第一步，草酸二乙酯在乙醇钠存在下与苯乙酮衍生物反应，形成取代的2,4-二氧代-4-苯基丁酸乙酯衍生物作为中间体（1a-j）。进一步将二氧代酯与水合肼在冰醋酸中制成悬浮液，得到新型5-（取代基）-1H-吡唑-3-羧酸乙酯（2a-j）衍生物。最终类似物（2a-j）的结构已通过元素分析、红外光谱、1H核磁共振和质谱得到证实。
所有元素分析、傅里叶变换红外光谱、1H核磁共振和质谱的值都很显著。抗炎活性测试表明，与对照组相比，5-（3,4-二甲氧基苯基）-1H-吡唑-3-羧酸乙酯（2f）和5-（2,3-二甲氧基苯基）-1H-吡唑-3-羧酸乙酯（2e）表现出显著的抗炎活性。
本研究结果表明，吡唑骨架上的取代可提高抗炎活性。
