Synthesis, Characterization of Ethyl 5-(substituted)-1H-pyrazole- 3-carboxylate Derivative as Potent Anti-inflammatory Agents.
Synthesis, Characterization of Ethyl 5-(substituted)-1H-pyrazole- 3-carboxylate Derivative as Potent Anti-inflammatory Agents.
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DOI：
10.2174/1871523017666180411155240
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发表时间：
2018-03
影响因子：
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通讯作者：
Khanal Pratik;K. Arun;S. Neha;Y. Bhumika;S. Anshuman;Gupta Sujeet Kumar
中科院分区：
文献类型：
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作者：
Khanal Pratik;K. Arun;S. Neha;Y. Bhumika;S. Anshuman;Gupta Sujeet Kumar
背景技术最近，吡唑衍生物显示出显著的抗肿瘤活性。非甾体类抗炎药有一定的副作用，主要是在治疗炎症过程中出现胃刺激和胃溃疡。因此，本论文旨在合成一系列新型吡唑类化合物，并对其抗炎活性进行评价。方法合成了一系列新的5-取代-1H-吡唑-3-羧酸乙酯（2a-j），并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，草酸二乙酯与苯乙酮衍生物在乙醇钠存在下反应生成取代的2，4-二氧代-4-苯基丁酸乙酯衍生物作为中间体（1a-j）。此外，由二氧代酯与水合肼在冰醋酸中制备悬浮液，得到新型5-（取代）-1H-吡唑-3-羧酸乙酯（2a-j）衍生物。最终类似物（2a-j）的结构已在元素分析、IR、1H NMR和质谱的基础上得到确认。结果元素分析、红外光谱、核磁共振氢谱和质谱的结果均较好。抗炎活性测试显示，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（2 e）表现出显著的抗炎活性。结论吡唑类化合物骨架上的取代可提高其抗炎活性。
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION The results of the current study indicate that the substitution at pyrazole scaffold could improve anti-inflammatory activity.