新型2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺的设计、合成、杀菌活性及分子对接研究

doi:10.6023/cjoc202206008

摘要/Abstract

为寻找结构新颖的嘧啶类杀菌剂, 以2-氯嘧啶-4-甲酸、1-甲基-4-吡唑硼酸频哪醇酯、取代苯胺或取代苄胺等为原料, 经Suzuki偶联和酰胺化反应合成了13种2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺类化合物, 其结构经过¹H NMR、¹³C NMR、IR、HRMS鉴定, 并利用X射线单晶衍射法确定了N-苄基-2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺(4h)的晶体结构. 初步测试了目标化合物对3种植物病原菌的杀菌活性, 在浓度为100 mg/L时, N-(4-甲基苯基)-2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺(4f)和N-(4-氯苄基)-2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺(4j)对水稻纹枯菌表现出较高的杀菌活性, 抑制率分别为85.3%和79.1%. 分子对接研究显示4f可与琥珀酸脱氢酶活性腔内的氨基酸残基形成2个氢键和1个阳离子-π相互作用.

关键词: 嘧啶, 酰胺, 琥珀酸脱氢酶抑制剂(SDHI), 杀菌活性, 分子对接

Abstract In order to develop novel pyrimidine fungicides, thirteen 2-(1-methyl-1H-pyrazol-4-yl) pyrimidine-4-carboxami- des were synthesized from 2-chloropyrimidine-4-carboxylic acid, 1-methyl-4-pyrazole borate pinacol ester, substituted anilines or substituted benzylamines as starting materials. The structures of target compounds were characterized by ¹H NMR, ¹³C NMR, IR, HRMS, and the crystal structure of N-benzyl-2-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamide (4h) was also determined by X-ray diffraction method. The preliminary fungicidal activities against three plant fungi were evaluated, and the results showed that at a dosage of 100 mg/L, N-(4-methyl)phenyl-2-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamide (4f) and N-(4-chlorobenzyl)-2-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamide (4j) possessed relatively high activities against Rhizoctonia solani with inhibitory rates of 85.3% and 79.1%, respectively. Molecular docking study showed that 4f can form two hydrogen bonds and one cation-π interaction with succinate dehydrogenase.

Key words: pyrimidine, carboxamide, succinate dehydrogenase (SDHI), fungicidal activity, molecular docking

引用此文

孙昌兴, 张福豪, 张欢, 李鹏辉, 姜林. 新型2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺的设计、合成、杀菌活性及分子对接研究[J]. 有机化学, 2023, 43(1): 229-235.

Changxing Sun, Fuhao Zhang, Huan Zhang, Penghui Li, Lin Jiang. Design, Synthesis, Fungicidal Activity and Molecular Docking Study of Novel 2-(1-Methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamides[J]. Chinese Journal of Organic Chemistry, 2023, 43(1): 229-235.

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化合物	取代基	茄子菌核菌		草莓灰霉菌		水稻纹枯菌
化合物	取代基	50 mg/L	100 mg/L	50 mg/L	100 mg/L	50 mg/L	100 mg/L
4a	H	52.0	68.5	52.0	68.8	50.6	73.7
4b	4-F	49.7	51.3	44.8	49.5	54.3	69.7
4c	2-Cl	17.7	18.4	17.2	26.5	41.9	62.7
4d	3-Cl	26.6	36.1	28.2	40.8	39.2	56.3
4e	4-Cl	19.6	23.9	26.2	37.2	39.4	43.4
4f	4-CH₃	54.1	66.3	49.7	61.6	66.2	85.3
4g	3-F-4-CH₃	24.6	30.1	37.4	45.3	61.3	70.6
4h	H	28.9	47.5	22.7	31.9	41.9	61.4
4i	4-F	35.6	50.3	34.1	37.2	41.0	56.5
4j	4-Cl	47.2	63.2	16.7	31.2	65.4	79.1
4k	4-Br	45.8	59.4	11.7	20.2	57.3	69.6
4l	4-CH₃	26.8	53.3	27.4	32.6	41.0	58.2
4m	4-CH₃O	26.0	44.7	11.0	22.6	27.6	45.4
Boscalid		97.8	100.0	74.6	90.0	90.2	100.0

化合物	取代基	茄子菌核菌		草莓灰霉菌		水稻纹枯菌
化合物	取代基	50 mg/L	100 mg/L	50 mg/L	100 mg/L	50 mg/L	100 mg/L
4a	H	52.0	68.5	52.0	68.8	50.6	73.7
4b	4-F	49.7	51.3	44.8	49.5	54.3	69.7
4c	2-Cl	17.7	18.4	17.2	26.5	41.9	62.7
4d	3-Cl	26.6	36.1	28.2	40.8	39.2	56.3
4e	4-Cl	19.6	23.9	26.2	37.2	39.4	43.4
4f	4-CH₃	54.1	66.3	49.7	61.6	66.2	85.3
4g	3-F-4-CH₃	24.6	30.1	37.4	45.3	61.3	70.6
4h	H	28.9	47.5	22.7	31.9	41.9	61.4
4i	4-F	35.6	50.3	34.1	37.2	41.0	56.5
4j	4-Cl	47.2	63.2	16.7	31.2	65.4	79.1
4k	4-Br	45.8	59.4	11.7	20.2	57.3	69.6
4l	4-CH₃	26.8	53.3	27.4	32.6	41.0	58.2
4m	4-CH₃O	26.0	44.7	11.0	22.6	27.6	45.4
Boscalid		97.8	100.0	74.6	90.0	90.2	100.0