中国新药杂志

1-苯甲酰基-4-（4-氯苄基）哌嗪衍生物的设计、合成以及抗炎活性研究

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王宏伟 ¹^,² , 刘万冬 ¹^,² , 李家明 ¹^,² , 金凡 ¹^,² , 钱诗虎 ¹^,²

中国新药杂志 | 实验研究 2021,30(6): 554-561

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中国新药杂志 |实验研究 2021 , 30 (6) : 554 -561

1-苯甲酰基-4-（4-氯苄基）哌嗪衍生物的设计、合成以及抗炎活性研究

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王宏伟¹^,², 刘万冬¹^,², 李家明¹^,², 金凡¹^,², 钱诗虎¹^,²

作者信息

¹安徽中医药大学药学院，合肥　230012

²安徽省中医药科学院药物化学研究所，合肥　230012

通讯作者:

李家明，男，博士，教授，博士生导师，主要从事药物化学设计与合成研究。联系电话：（0551）68129147，E-mail：lijiaming2017@sina.com。

作者简介:

王宏伟，男，研究生，主要从事药物化学设计与合成研究。E-mail：18119629721@163.com。

Design, synthesis and anti-inflammatory activity research of 1-benzoyl-4-(phenoxyacetyl) piperazine derivatives

Hong-wei WANG¹^,², Wan-dong LIU¹^,², Jia-ming LI¹^,², Fan JIN¹^,², Shi-hu QIAN¹^,²

Affiliations

¹College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China

²Department of Medicinal Chemistry, Anhui Academy of Chinese Medicine, Hefei 230012, China

出版时间: 2021-03-30

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摘要

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目的：

以1-苯甲酰基-4-（4-氯苄基）哌嗪为先导化合物，经进一步的结构优化，期望获得一类抗炎活性更好的多靶点抑制剂。

方法：

以取代苯甲酸为起始原料，经取代、酰化反应合成18个目标化合物。测定所有化合物对脂多糖（lipopolysaccharide，LPS）诱导RAW264.7细胞分泌肿瘤坏死因子（tumor necrosis factor，TNF）-α和白细胞介素（interleukin，IL）-6的抑制作用，并对活性较好的化合物进行分子对接。

结果：

所有化合物均经¹H NMR，¹³C NMR，HRMS确定其结构，化合物3d，8k对TNF-α的分泌具有较好的抑制活性，化合物3b，3d对IL-6的分泌具有较好的抑制活性。

结论：

化合物3d对LPS诱导RAW264.7细胞分泌TNF-α和IL-6具有较好的抑制活性，有进一步研究的价值。

关键词

多靶点抑制剂 / 抗炎 / TNF-α / IL-6

Abstract

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Objective:

To obtain a series of multi-target inhibitors with better anti-inflammatory activity by using 1-benzoyl-4-(phenoxyacetyl) piperazine as the lead compound followed by further structure optimization.

Methods:

Substituted benzoic acid was used as a starting material, and 18 target compounds were synthesized through substitution and acylation reactions. The inhibitory effects of all compounds on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion in RAW264.7 cells were measured, and molecular docking was performed on the compounds with better anti-inflammatory activity.

Results:

The structures of all the compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. Compounds 3d and 8k demonstrated better inhibitory activity on TNF-α secretion, and compounds 3b and 3d showed better inhibitory activity on IL-6 secretion.

Conclusion:

Compound 3d has good inhibitory activity on TNF-α and IL-6 secretion in RAW264.7 cells induced by LPS, and is worthy of further study.

Key words

multi-target inhibitors / anti-inflammation / TNF-α / IL-6

引用本文

王宏伟, 刘万冬, 李家明, 金凡, 钱诗虎. 1-苯甲酰基-4-（4-氯苄基）哌嗪衍生物的设计、合成以及抗炎活性研究. 中国新药杂志, 2021 , 30 (6) : 554 -561 .

Hong-wei WANG, Wan-dong LIU, Jia-ming LI, Fan JIN, Shi-hu QIAN. Design, synthesis and anti-inflammatory activity research of 1-benzoyl-4-(phenoxyacetyl) piperazine derivatives[J]. Chinese Journal of New Drugs, 2021 , 30 (6) : 554 -561 .

基金

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安徽省自然科学基金资助项目(1508085MB3)

参考文献

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参考文献引证文献

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2021年第30卷第6期

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首发时间：2026-10-29
出版时间：2021-03-30

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出版历史

录用日期：2020-05-18

基金

安徽省自然科学基金资助项目(1508085MB3)

作者信息

¹安徽中医药大学药学院，合肥　230012

²安徽省中医药科学院药物化学研究所，合肥　230012

通讯作者:

李家明，男，博士，教授，博士生导师，主要从事药物化学设计与合成研究。联系电话：（0551）68129147，E-mail：lijiaming2017@sina.com。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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