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• 1, 1-二芳基化合物在医药和农药产品中都有着广泛而重要的应用和较高的出现频率^[1~3], 如在农药上, 鼠特灵(Norbormide)用作灭鼠剂^{[4, 5]}, 充当血管收缩剂和钙通道阻滞剂, 对大鼠有选择性毒性, 而对其他物种毒性较低; 日本石原公司开发的Pyriofenone^[6]对谷类、葡萄和蔬菜粉霉病有非常好的杀菌活性, 尤其对灰霉病有特效; 在医药上, 抗心律失常的药物磷酸丙吡胺(Disopyramide)^[7]和吡美诺(Pimenol)^[8]、脂肪酸酰胺水解酶(FAAH)抑制剂VER-24052^[9]和抗组胺药氯苯吡醇胺(Carbinoxamine)^{[10, 11]}等, 都含有1, 1-二芳基结构单元(其中一个芳基为吡啶基)(图 1).可见1, 1-二芳基结构是一类重要的结构单元.

  图 1

  

  图 1.  代表性1-芳基-1-吡啶基医药和农药品种

  Figure 1.  Representative 1-aryl-1-pyridine based medicine and pesticide varieties

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  因此, 基于1, 1-二芳基结构的广泛应用以及我们提出的“分子插件”(The Plug-in Molecules)^[12]的概念, 并结合吡啶杂环在农药分子中的独特作用, 我们建立了吡啶二芳酮(1)分子插件数据库, 并成功应用于新农药开发中.在前期工作中, 我们以该类分子插件为基础, 合成了多个系列的新型活性化合物(图 2), 如通过Wittig-Horner反应合成了二芳基丙烯酰胺类化合物, 开发出了新型杀菌剂丁吡吗啉(2)^[13~16], 它既能影响病原菌细胞壁合成物质的极性分布, 又能通过抑制病原菌细胞呼吸链复合物Ⅲ的活性而抑制其能量合成, 现已商品化投入市场应用; 通过Knoevenagel反应合成了水合丁吡吗啉(3)及其类似物^[17], 其中化合物3的活性与丁吡吗啉相当; 以其肟为原料合成的甲氧丙烯酸酯类化合物4对小麦白粉病、黄瓜炭疽病具有很好的防效, 并对稻梨孢的孢子萌发具有强烈的抑制效果^[18]; 以其肟与双草醚形成的肟酯5对稗草的除草活性优于嘧啶肟草醚^[19]等.可见吡啶二芳酮类是一类功能强大的分子插件.

  图 2

  

  图 2.  吡啶二芳酮类分子插件及其应用

  Figure 2.  Aplication examples of arylpyridinylmethanone plug-in molecules

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  嘧菌腙(Ferimzone, 6)是由日本武田公司开发的一种农用杀菌剂, 主要防治水稻上由稻尾声孢、稻长蠕孢和稻梨孢等病原菌引起的病害.其能干扰真菌细胞膜的通透性, 从而影响离子和小分子的流通^[20].本研究以嘧菌腙为母体化合物, 设计并合成了一系列芳基吡啶酮腙类化合物Ⅲ (Eq. 1), 将吡啶杂环、嘧啶杂环和腙单元有效整合到同一分子中, 测定了它们的杀菌活性, 并对其构效关系进行了初步探讨.

  (1)

  1.   结果与讨论

  1.1   目标化合物的合成

  目标化合物的合成见Scheme 1所示, 以4, 6-二甲氧基-2-甲磺酰基嘧啶为起始原料, 首先通过肼解^[21]得到4, 6-二甲氧基-2-肼基嘧啶(Ⅱ), 此步反应通过抽滤可直接得到白色固体产物, 收率85%.然后用化合物Ⅱ与各类芳酮进行亲核加成消除反应得到腙^[22]Ⅲ-1~Ⅲ-26.大部分化合物可通过重结晶直接得到, 少数化合物通过柱层析后结晶获得.化合物结构及反应收率如表 1所示.

  图式 1

  

  图式 1.  目标化合物的合成

  Scheme 1.  Synthesis of target compounds

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  表 1

  

  表 1  目标化合物结构及收率

  Table 1.  Structure and yield of target compounds

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  Compd.	R1	R2	Yield/%
  Ⅲ-1	Ph	Ph	75
  Ⅲ-2	4-tBuC6H4	4-NO2C6H4	82
  Ⅲ-3	CH3	2-CH3C6H4	67
  Ⅲ-4	4-tBuC6H4	3-Pyridyl	88
  Ⅲ-5	3, 4-Cl2C6H3	3-Pyridyl	62
  Ⅲ-6	4-CH3C6H4	4-Pyridyl	90
  Ⅲ-7	4-iPrC6H4	4-Pyridyl	68
  Ⅲ-8	3, 4-(CH3)2C6H3	4-Pyridyl	65
  Ⅲ-9	2-CH3-3-ClC6H3	4-Pyridyl	70
  Ⅲ-10	4-BrC6H4	4-Pyridyl	61
  Ⅲ-11	4-BrC6H4	2-Cl-3-pyridyl	63
  Ⅲ-12	4-tBuC6H4	2-Cl-3-pyridyl	56
  Ⅲ-13	4-CH3C6H4	2-Cl-3-pyridyl	55
  Ⅲ-14	3, 4-Cl2C6H3	2-Cl-3-pyridyl	64
  Ⅲ-15	2, 4-(CH3)2C6H3	3-Cl-4-pyridyl	91
  Ⅲ-16	4-CH3C6H4	3-Cl-4-pyridyl	93
  Ⅲ-17	3, 4-(CH3)2C6H3	3-Cl-4-pyridyl	78
  Ⅲ-18	4-BrC6H4	3-Cl-4-pyridyl	72
  Ⅲ-19	4-PhC6H4	3-Cl-4-pyridyl	91
  Ⅲ-20	3-NO2-4-CH3C6H3	3-Cl-4-pyridyl	68
  Ⅲ-21	4-tBuC6H4	3-Cl-4-pyridyl	88
  Ⅲ-22	4-CH3C6H4	4-Cl-3-pyridyl	64
  Ⅲ-23	2, 4-(CH3)2C6H3	4-Cl-3-pyridyl	65
  Ⅲ-24	4-BrC6H4	4-Cl-3-pyridyl	89
  Ⅲ-25	4-(4ꞌ-Br-C6H4)C6H4	4-Cl-3-pyridyl	66
  Ⅲ-26	3, 5-Cl2C6H3	4-Cl-3-pyridyl	61

  1.2   抑菌活性初筛测定

  通过菌丝生长速率法^[23]测试了目标化合物在0.07 mmol/L浓度下对棉花立枯(Rhizoctonia Cotton, RC)、水稻稻瘟(Pyricularia oryzae Cav, PC)、番茄灰霉(Botrytis cinerea, BC)、番茄晚疫(Phytophthora infestans, PI)、水稻纹枯(Thanatephorus cucumeris, TC)、小麦赤霉(FusaHum graminearum Sehw, FS)、油菜菌核(Sclerotinia sclerotiorum, SS)和玉米大斑(Exserohilum turcicum, ET)八种病原菌的抑制效果, 结果列于表 2.

  表 2

  

  表 2  目标化合物Ⅲ-1~Ⅲ-26的抑菌活性(抑制率/%)^a

  Table 2.  Antifungal activity of title compounds Ⅲ-1~Ⅲ-26 (inhibitory rate/%)

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  Compd.	RC	PC	BC	PI	TC	FS	SS	ET
  嘧菌腙	32.76	55.19	69.74	34.62	52.31	8.48	98.30	90.80
  Ⅲ-1	19.38	51.75	42.92	62.50	25.46	38.45	52.45	89.68
  Ⅲ-2	0	2.26	8.80	4.43	0	19.98	11.34	46.17
  Ⅲ-3	20.29	42.75	84.86	65.23	41.48	33.06	100	91.66
  Ⅲ-4	43.51	14.33	24.68	45.51	32.41	30.61	8.30	0
  Ⅲ-5	0	26.69	38.82	61.01	39.41	44.61	33.22	57.97
  Ⅲ-6	17.94	25.41	32.19	40.17	29.40	35.92	25.76	81.49
  Ⅲ-7	20.62	17.77	35.62	36.97	13.89	26.23	10.97	84.52
  Ⅲ-8	31.13	37.96	57.51	57.69	42.13	46.29	27.95	84.07
  Ⅲ-9	29.69	41.41	66.09	55.98	43.98	49.05	25.76	91.25
  Ⅲ-10	28.04	27.13	61.80	55.98	26.39	37.76	43.96	84.19
  Ⅲ-11	25.77	46.82	74.68	65.17	38.89	37.07	74.28	89.01
  Ⅲ-12	20.21	39.44	66.09	53.63	29.63	42.14	60.94	80.71
  Ⅲ-13	0	38.46	51.69	40.74	42.17	40.23	68.60	68.40
  Ⅲ-14	1.48	42.53	47.62	66.08	27.19	34.48	65.89	75.93
  Ⅲ-15	3.09	3.00	6.87	0.21	6.02	5.49	11.45	1.30
  Ⅲ-16	17.53	5.71	33.48	50.85	8.33	8.71	32.31	5.79
  Ⅲ-17	0	14.70	51.01	44.33	13.83	29.83	53.20	20.52
  Ⅲ-18	0	17.64	43.79	50.46	68.91	30.10	50.77	22.57
  Ⅲ-19	0	9.05	15.57	11.82	8.30	15.87	17.28	86.87
  Ⅲ-20	0	7.46	32.05	46.66	6.91	28.19	36.46	75.24
  Ⅲ-21	0	2.71	20.31	6.54	1.15	17.51	27.55	20.52
  Ⅲ-22	16.91	26.88	57.08	47.01	19.91	27.39	53.42	91.48
  Ⅲ-23	0	38.91	45.37	57.63	16.36	26.54	48.34	47.88
  Ⅲ-24	0	12.67	36.11	52.99	18.90	32.56	52.39	0
  Ⅲ-25	0	0	7.00	6.76	0	1.37	43.75	86.19
  Ⅲ-26	0	22.85	34.31	34.20	13.83	29.28	45.10	62.07
  a c＝0.07 mmol•L-1.

  由表 2抑制率数据可知:在0.07 mmol/L浓度下, 对于棉花立枯病菌、水稻稻瘟病菌来说, 除化合物Ⅲ-4对棉花立枯病菌抑制活性优于对照药剂嘧菌腙外, 其他化合物表现出较差的抑制活性.对于番茄灰霉病菌来说, 化合物Ⅲ-3和Ⅲ-11表现出优秀的抑制活性, 抑制率分别达到84.86%和74.68%, 有进一步改造的潜力.对于番茄晚疫病菌来说, 约7/9的化合物抑制活性高于对照药剂嘧菌腙, 其中化合物Ⅲ-3, Ⅲ-11和Ⅲ-14抑制率接近嘧菌腙的2倍.对于水稻纹枯病菌, 化合物Ⅲ-18明显优于其他25个化合物, 且比对照药剂嘧菌腙抑制率高17%.对于小麦赤霉病菌, 相比较基本没有药效的嘧菌腙, 所设计的大多数化合物有中等程度的药效, 可见吡啶二芳酮基团的引入对于防治小麦赤霉病菌起到很好的作用, 这对后续防治小麦赤霉病菌的药剂开发有借鉴意义.对于油菜菌核病菌, 化合物Ⅲ-3抑制活性最佳, 且高于嘧菌腙, 其他化合物抑制活性表现较差.对于玉米大斑病菌, 化合物Ⅲ-3和Ⅲ-22抑制活性好于对照药剂, 化合物Ⅲ-1和Ⅲ-11也有和对照药剂相当的活性.总的来说, 所设计合成的26个化合物均表现出一定的抑制活性, 体现出化合物设计的合理性, 同时化合物Ⅲ-3, Ⅲ-11, Ⅲ-14和Ⅲ-18整体表现出较好的抑制活性, 有进一步研究的价值.

  化合物的构效关系: (1)当R¹基团为4-CH₃-C₆H₄时, R²基团分别为4-Pyridyl (Ⅲ-6), 2-Cl-3-Pyridyl (Ⅲ-13), 3-Cl-4-Pyridyl (Ⅲ-16)和4-Cl-3-Pyridyl (Ⅲ-22), 通过比较其抑制活性可以看出, 对于番茄灰霉病菌、油菜菌核病菌和稻瘟病菌, 化合物Ⅲ-13和Ⅲ-22活性明显高于另外两个化合物, 对于其他6种病原菌, 这4个化合物没有表现出明显的规律性, 可见R²基团为3-Pyridyl有一定优势. (2)当R¹基团为4-Br-C₆H₄时, R²基团分别为4-Py (Ⅲ-10), 2-Cl-3-Pyridyl (Ⅲ-11), 3-Cl-4-Pyridyl (Ⅲ-18)和4-Cl-3-Pyridyl (Ⅲ-24), 比较Ⅲ-11和Ⅲ-24的抑制活性数据, 可知对于筛选的所有8种病原菌, 化合物Ⅲ-11抑制活性均明显优于化合物Ⅲ-24, 可见R²基团3-吡啶环上氯原子位于2-位的抑制活性优于4-位.比较Ⅲ-10和Ⅲ-18的抑制活性数据则没有发现明显规律性. (3)当R¹基团为3, 4-(CH₃)₂C₆H₃时, R²基团分别为4-Pyridyl (Ⅲ-8)和3-Cl-4-Pyridyl (Ⅲ-13)时, 对于除油菜菌核病菌外的7种病原菌, 化合物Ⅲ-8抑制活性均明显优于化合物Ⅲ-13, 可见R²基团4-吡啶环上3-位引入氯原子不利于提高其抑制活性. (4)当R²基团为4-Pyridyl, R¹基团分别为4-CH₃C₆H₄ (Ⅲ-6), 4-ⁱPrC₆H₄ (Ⅲ-7), 3, 4-(CH₃)₂C₆H₃ (Ⅲ-8)和2-CH₃-3-ClC₆H₃ (Ⅲ-9), 通过分析其抑制活性数据可以发现, 多取代的Ⅲ-8和Ⅲ-9对于8种病原菌的抑制效果明显好于单取代的化合物Ⅲ-6和Ⅲ-7.同时当R²基团为3-Cl-4-Pyridyl时, R¹基团分别为3, 4- (CH₃)₂C₆H₃ (Ⅲ-17)和4-CH₃C₆H₄ (Ⅲ-16), 分析其生测数据, 发现对除棉花立枯病菌外的7种病原菌, 多取代的Ⅲ-17明显比单取代Ⅲ-16抑制效果好, 但当R¹基团为2, 4-(CH₃)₂C₆H₃ (Ⅲ-15)时, 活性相比Ⅲ-17下降很明显, 说明多取代的位置对活性影响也十分关键.

  1.3   精密毒力的测定

  经初步实验筛选, 选取活性较好的化合物Ⅲ-3, Ⅲ-11, Ⅲ-14和Ⅲ-18进行油菜菌核(Sclerotinia sclerotiorum)、水稻稻瘟(Pyricularia oryzae Cav)、番茄晚疫(Phytophthora infestans)、番茄灰霉(Botrytis cinerea)和水稻纹枯(Thanatephorus cucumeris)五种病原菌的精密毒力实验, 实验采用生长速率法测定140, 70, 35, 3.5, 0.35和0 μmol•L^-1浓度下的抑制率, 实验均重复三次, EC₅₀通过社会科学统计程序(SPSS)计算, 结果列于表 3.

  表 3

  

  表 3  部分化合物的EC₅₀

  Table 3.  EC₅₀ of part title compounds

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  病原菌	化合物	EC50/(μmol•L-1)	R2	毒力回归方程
  SS	嘧菌腙	52.29±1.54	0.999	y＝1.19x-0.78
  	Ⅲ-3	36.39±6.68	0.938	y＝2.13x-2.77
  	Ⅲ-11	60.27±5.74	0.979	y＝1.62x-2.9
  	Ⅲ-14	67.96±5.81	0.992	y＝0.78x-1.43
  	Ⅲ-18	＞140
  PC	嘧菌腙	48.11±4.99	0.940	y＝1.19x-2.05
  	Ⅲ-3	99.04±5.64	0.999	y＝1.09x-2.18
  	Ⅲ-11	110.97±5.01	0.984	y＝1.24x-2.53
  	Ⅲ-14	＞140
  	Ⅲ-18	＞140
  PI	嘧菌腙	96.99±9.06	0.999	y＝2.44x-4.85
  	Ⅲ-3	55.96±7.57	0.992	y＝2.04x-3.53
  	Ⅲ-11	74.71±3.77	0.970	y＝0.92x-1.73
  	Ⅲ-14	61.33±2.00	0.935	y＝0.53x-0.96
  	Ⅲ-18	99.81±10.74	0.971	y＝0.75x-1.5
  BC	嘧菌腙	31.38±1.83	0.821	y＝1.53x-2.26
  	Ⅲ-3	22.18±6.03	0.953	y＝1.51x-1.96
  	Ⅲ-11	＞140
  	Ⅲ-14	＞140
  	Ⅲ-18	＞140
  TC	嘧菌腙	93.33±9.41	0.998	y＝2.2x-4.33
  	Ⅲ-3	＞140
  	Ⅲ-11	＞140
  	Ⅲ-14	＞140
  	Ⅲ-18	＜0.35	0.998	y＝0.11x+0.18

  通过表 3数据可以看出, 所有生测的相关系数均大于0.8, 可见浓度与抑制率数据具有很强的相关性.对于油菜菌核病菌, 化合物Ⅲ-3的EC₅₀比嘧菌腙降低了一半, 同时化合物Ⅲ-3对番茄晚疫病菌和番茄灰霉病菌上的药效是嘧菌腙的1.5倍以上.化合物Ⅲ-11和Ⅲ-14在番茄晚疫病菌上的EC₅₀值比嘧菌腙明显要低.有趣的是, 化合物Ⅲ-18在水稻纹枯病菌的EC₅₀值比嘧菌腙要低260倍以上, 可见其在很低的浓度就能起到很好的抑制效果, 通过其毒力回归方程可以发现, 化合物Ⅲ-18斜率很低, 说明该化合物即使浓度变化很大, 其药效影响变化并不大.

  2.   结论

  通过分子插件原理, 设计并合成了26个芳基吡啶酮腙类化合物, 除Ⅲ-1是已知化合物外, 共有25个新化合物.测试了棉花立枯、水稻稻瘟、番茄灰霉、番茄晚疫、水稻纹枯、小麦赤霉、油菜菌核和玉米大斑八种病原菌的抑制效果, 发现大多数化合物都有一定的抑制活性, 可见分子插件原理可以实现化合物的快速合成与筛选.同时化合物Ⅲ-3和Ⅲ-18对病原菌抑制效果明显高于对照药嘧菌腙, Ⅲ-11, Ⅲ-14和其他部分化合物也有不弱于嘧菌腙的效果, 本研究对新型杀菌剂的设计合成提供有益的参考, 具有重要的借鉴意义.

  3.   实验部分

  3.1   仪器与试剂

  Bruker Avance DPX300超导核磁共振仪(TMS为内标); 安捷伦ESI-Q-TOF型高分辨质谱仪; Yanagimoto MFG Co.熔点测定仪, 温度计未经校正; 宁波江南仪器厂RXZ智能型光照培养箱; 所有试剂国产市售分析纯, 无水溶剂按标准方法处理.

  3.2   实验方法

  3.2.1   嘧菌腙(6)的合成

  100 mL三口瓶中加入4.6-二甲基-2-氯嘧啶(2 g, 14.1 mmol)、磁子和40 mL乙醇, 于室温搅拌.然后加入水合肼(0.92 mL, 15.5 mmol).加热回流8 h, 冷却抽滤得淡黄色固体4.6-二甲基-2-肼基嘧啶1.75 g, 收率90%.

  取1 g 4.6-二甲基-2-肼基嘧啶(7.2 mmol)加入100 mL圆底烧瓶, 加入邻甲基苯乙酮(0.92 g, 6.9 mmol)、磁子和40 mL无水甲醇.常温搅拌10 min后加入1滴乙酸, 加热回流8 h.冷却抽滤得淡黄色固体1.7 g.收率93%. m.p. 182.4~183.6 ℃(文献值^[24]: m.p. 178~180 ℃); ¹H NMR (300 MHz, CDCl₃) δ: 7.76 (s, 1H), 7.30~7.14 (m, 3H), 7.04~6.98 (m, 1H), 6.39 (s, 1H), 2.28 (s, 6H), 2.26 (s, 3H), 2.18 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 167.70, 159.25, 149.54, 134.46, 130.61, 128.89, 126.56, 126.40, 111.94, 24.71, 23.59, 18.62; HRMS (ESI) calcd for C₁₅H₁₉N₄ (M+H)⁺ 255.1604 found 255.1599.

  3.2.2   目标化合物Ⅲ-1~Ⅲ-26的合成

  250 mL三口瓶中加入4.6-二甲氧基-2-甲磺酰基嘧啶(20 g, 91.7 mmol)和磁子, 加入120 mL乙醇于室温搅拌.然后加入水合肼(5.8 mL, 100.9 mmol), 加热回流8 h.冷却抽滤得白色固体13.3 g, 收率85%.

  取4.6-二甲氧基-2-肼基基嘧啶(0.5 g, 2.9 mmol)加入100 mL圆底烧瓶, 加入二苯甲酮(0.51 g, 2.8 mmol)、磁子和40 mL无水甲醇.常温搅拌10 min后加入1滴乙酸, 加热回流8 h, 薄层色谱(TLC)监测反应完毕.柱层析分离得白色固体Ⅲ-1.用同样的方法得到目标化合物Ⅲ-2~Ⅲ-26.

  苯甲酰基苯-4, 6-二甲氧基嘧啶-2-腙(Ⅲ-1):收率75%. m.p. 158.1~159.2 ℃; ¹H NMR (300 MHz, DMSO-d₆) δ: 8.19 (s, 1H), 7.68~7.61 (m, 2H), 7.59~7.47 (m, 3H), 7.35~7.28 (m, 5H), 5.57 (s, 1H), 3.91 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.10, 158.55, 148.44, 137.35, 132.01, 129.41, 129.22, 128.60, 128.40, 127.84, 126.82, 81.15, 53.58.

  2-[2'-(4''-叔丁基-苯基)(4ꞌꞌ-硝基-苯基)-亚甲基]-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-2):收率82%. m.p. 213.4~214.9 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.41 (s, 1H), 8.19~8.12 (m, 2H), 7.82~7.76 (m, 2H), 7.64~7.59 (m, 2H), 7.26~7.21 (m, 2H), 5.62 (s, 1H), 3.93 (s, 6H), 1.40 (s, 9H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.22, 158.19, 153.05, 147.26, 146.02, 143.66, 128.03, 127.55, 127.26, 126.71, 123.12, 53.77, 34.65, 30.90; HRMS (ESI) calcd for C₂₃H₂₆N₅O₄ (M+H)⁺ 436.1979, found 436.1980.

  2ꞌ-甲基乙酰基苯-4, 6-二甲氧基嘧啶-2-腙(Ⅲ-3):收率67%. m.p. 150.6~151.2 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.12 (s, 1H), 7.39~7.32 (m, 1H), 7.22~7.18 (m, 3H), 5.59 (s, 1H), 3.92 (s, 6H), 2.52 (s, 3H), 2.28 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.05, 159.12, 147.92, 139.07, 135.79, 130.70, 127.97, 127.71, 125.29, 81.29, 53.57, 20.87, 15.82; HRMS (ESI) calcd for C₁₅H₁₉N₄O₂ (M+H)⁺ 287.1503, found 287.1499.

  2-(2'-((4''-叔丁基-苯基)(吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-4):收率88%. m.p. 180.6~181.9 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.52 (dd, J＝4.6, 1.6 Hz, 2H), 8.40 (s, 1H), 7.57 (d, J＝8.5 Hz, 2H), 7.47 (dd, J＝4.6, 1.6 Hz, 2H), 7.21 (d, J＝8.5 Hz, 2H), 5.58 (s, 1H), 3.90 (s, 6H), 1.36 (s, 9H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.14, 158.21, 152.84, 149.46, 145.64, 144.72, 128.03, 127.31, 126.53, 120.60, 81.55, 53.64, 34.57, 30.87; HRMS (ESI) calcd for C₂₂H₂₆N₅O₂ (M+H)⁺ 392.2081, found 392.2078.

  2-(2'-((3, 4''-二氯-苯基)(吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-5):收率62%. m.p. 189.8~190.9 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.74 (d, J＝2.2 Hz, 1H), 8.51 (dd, J＝4.8, 1.6 Hz, 1H), 8.24 (s, 1H), 7.91 (d, J＝8.1 Hz, 1H), 7.70 (d, J＝8.3 Hz, 2H), 7.28~7.15 (m, 3H), 5.58 (s, 1H), 3.88 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.06, 158.24, 149.40, 148.12, 144.13, 133.46, 133.01, 132.78, 130.02, 129.62, 124.09, 122.76, 81.87, 53.65; HRMS (ESI) calcd for C₁₈H₁₆C_l2N₅O₂ (M+H)⁺ 404.0676, found 404.0675.

  2-(2'-((4''-甲基-苯基)(吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-6):收率90%. m.p. 169.8~170.5 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.55 (dd, J＝4.7, 1.6 Hz, 2H), 8.39 (s, 1H), 7.49 (dd, J＝4.7, 1.6 Hz, 2H), 7.39 (d, J＝8.1 Hz, 2H), 7.19 (d, J＝8.0 Hz, 2H), 5.61 (s, 1H), 3.92 (s, 6H), 2.46 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.11, 158.19, 149.50, 145.69, 144.70, 139.79, 130.31, 128.20, 127.40, 120.59, 81.80, 53.63, 21.10; HRMS (ESI) calcd for C₁₉H₂₀N₅O₂ (M+H)⁺ 350.1612, found 350.1613.

  2-(2'-((4''-异丙基-苯基)(吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-7):收率68%. m.p. 173.5~174 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.56 (dd, J＝4.6, 1.6 Hz, 2H), 8.43 (s, 1H), 7.51 (dd, J＝4.6, 1.6 Hz, 2H), 7.45 (d, J＝8.1 Hz, 2H), 7.24 (d, J＝8.1 Hz, 2H), 5.62 (s, 1H), 3.93 (s, 6H), 3.01 (dt, J＝13.8, 6.9 Hz, 1H), 1.34 (d, J＝6.9 Hz, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.11, 158.20, 150.51, 149.47, 145.65, 144.71, 128.27, 127.68, 120.58, 81.62, 53.61, 33.71, 23.44; HRMS (ESI) calcd for C₂₁H₂₄N₅O₂ (M+H)⁺ 378.1925, found 378.1922.

  2-(2'-((3, 4''-二甲基-苯基)(吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-8):收率65%. m.p. 191.2~192 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.62~8.48 (m, 3H), 7.51 (dd, J＝4.6, 1.6 Hz, 2H), 7.33~7.25 (m, 1H), 7.02 (d, J＝7.0 Hz, 2H), 5.60 (s, 1H), 3.91 (s, 6H), 2.32 (d, J＝4.4 Hz, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.00, 158.21, 149.44, 145.84, 144.77, 138.35, 138.12, 130.67, 129.00, 127.88, 125.56, 120.57, 81.74, 53.53, 19.50, 19.34; HRMS (ESI) calcd for C₂₀H₂₂N₅O₂ (M+H)⁺ 364.1768, found 364.1769.

  2-(2'-((2''-甲基-3''-氯-苯基)(吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-9):收率70%. m.p. 152.0~152.8 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.59 (s, 1H), 8.47 (dd, J＝4.6, 1.6 Hz, 2H), 7.46~7.37 (m, 3H), 7.09~6.96 (m, 2H), 5.53 (d, J＝0.9 Hz, 1H), 3.81 (s, 6H), 2.35 (d, J＝3.3 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 171.88, 158.07, 149.46, 144.26, 144.21, 144.18, 143.72, 137.90, 137.86, 135.89, 135.67, 132.03, 130.49, 130.25, 129.58, 129.07, 128.63, 126.92, 126.45, 120.32, 82.17, 53.52, 19.83, 19.66; HRMS (ESI) calcd for C₁₉H₁₉ClN₅O₂ (M+H)⁺ 384.1222, found 384.1219.

  2-(2'-((4''-溴-苯基)(吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-10):收率61%. m.p. 180.8~182 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.85 (dd, J＝4.3, 1.6 Hz, 2H), 7.98 (s, 1H), 7.43 (s, 4H), 7.25 (dd, J＝4.3, 1.6 Hz, 2H), 5.59 (s, 1H), 3.89 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) δ 172.09, 158.17, 151.24, 143.94, 139.65, 135.00, 131.25, 127.92, 123.33, 123.08, 81.92, 53.66; HRMS (ESI) calcd for C₁₈H₁₇BrN₅O₂ (M+H)⁺ 414.0560, found 414.0564.

  2-(2'-((4''-溴-苯基)(2''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-11):收率63%. m.p. 190~190.9 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.60 (dd, J＝4.8, 2.0 Hz, 1H), 7.91 (s, 1H), 7.66 (dd, J＝7.5, 2.0 Hz, 1H), 7.50~7.39 (m, 5H), 5.61 (s, 1H), 3.91 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.08, 158.10, 151.12, 150.13, 141.77, 139.77, 134.67, 131.37, 127.53, 127.10, 123.28, 123.09, 81.95, 53.78; HRMS (ESI) calcd for C₁₈H₁₆Br- ClN₅O₂ (M+H)⁺ 448.0170, found 448.0166.

  2-(2'-((4''-叔丁基-苯基)(2''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-12):收率56%. m.p. 179.1~179.3 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.54 (dd, J＝4.8, 2.0 Hz, 1H), 7.85 (s, 1H), 7.60 (dd, J＝7.5, 2.0 Hz, 1H), 7.44~7.33 (m, 5H), 5.55 (s, 1H), 3.85 (s, 6H). 1.33 (s, 9H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.13, 158.16, 151.11, 150.16, 141.71, 139.78, 134.68, 131.37, 127.53, 127.13, 123.27, 123.08, 81.96, 53.75. 34.65, 30.88; HRMS (ESI) calcd for C₂₂H₂₅ClN₅O₂ (M+H)⁺ 426.1691, found 426.1688.

  2-(2'-((4''-甲基-苯基)(2''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-13):收率55%. m.p. 173.9~174.4 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.59 (dd, J＝4.8, 2.0 Hz, 1H), 7.89 (s, 1H), 7.66 (dd, J＝7.5, 2.0 Hz, 1H), 7.50~7.41 (m, 3H), 7.14 (d, J＝8.1 Hz, 2H), 5.59 (s, 1H), 3.91 (s, 6H), 2.34 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.07, 158.32, 150.82, 150.10, 143.13, 139.78, 139.16, 132.94, 128.92, 127.85, 126.08, 122.98, 81.63, 53.70, 20.99; HRMS (ESI) calcd for C₁₉H₁₉ClN₅O₂ (M+H)⁺ 384.1222, found 384.1224.

  2-(2'-((3, 4''-二氯-苯基)(2''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-14):收率64%. m.p. 178.2~179 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.61 (dd, J＝4.8, 2.0 Hz, 1H), 7.95 (s, 1H), 7.70~7.61 (m, 2H), 7.52~7.48 (m, 1H), 7.40~7.32 (m, 2H), 5.62 (s, 1H), 3.90 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.13, 158.02, 151.32, 150.11, 140.31, 139.78, 135.82, 132.87, 132.62, 130.15, 127.62, 126.62, 125.12, 123.17, 82.19, 53.78; HRMS (ESI) calcd for C₁₈H₁₅C_l3N₅O₂ (M+H)⁺ 438.0286, found 438.0285.

  2-(2'-((2, 4''-二甲基-苯基)(3''-氯-吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-15):收率91%. m.p. 207.8~208 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.28 (d, J＝5.3 Hz, 1H), 8.17 (s, 1H), 7.44 (dd, J＝5.3, 1.3 Hz, 1H), 7.39 (s, 1H), 7.17 (d, J＝13.3 Hz, 2H), 6.99 (d, J＝7.6 Hz, 1H), 5.60 (s, 1H), 3.88 (s, 6H), 2.38 (s, 3H), 2.06 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.11, 157.99, 151.72, 149.27, 147.59, 144.47, 140.15, 136.24, 131.88, 128.14, 127.81, 126.24, 120.61, 118.88, 82.01, 53.69, 20.98, 18.81; HRMS (ESI) calcd for C₂₀H₂₁ClN₅O₂ (M+H)⁺ 398.1378, found 398.1376.

  2-(2'-((4''-甲基-苯基)(3''-氯-吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-16):收率93%. m.p. 200.7~201.2 ℃; ¹H NMR (300 MHz, DMSO) δ: 8.44~8.27 (m, 2H), 7.61~7.55 (m, 1H), 7.51~7.36 (m, 3H), 7.31~7.12 (m, 2H), 5.61 (d, J＝6.3 Hz, 1H), 3.90 (s, 6H), 2.44 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.08, 157.99, 157.85, 151.71, 151.58, 149.28, 149.13, 147.96, 147.39, 144.30, 142.64, 140.11, 136.24, 130.48, 130.26, 129.78, 128.25, 128.08, 126.79, 121.11, 120.90, 119.25, 119.05, 82.49, 82.10, 53.72, 53.67, 21.12; HRMS (ESI) calcd for C₁₉H₁₉ClN₅O₂ (M+H)⁺ 384.1222, found 384.1221.

  2-(2'-((3, 4''-二甲基-苯基)(3''-氯-吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-17):收率78%. m.p. 171.7~171.9 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.44 (s, 1H), 8.29 (d, J＝5.3 Hz, 1H), 7.49 (dd, J＝5.3, 1.5 Hz, 1H), 7.42 (d, J＝0.9 Hz, 1H), 7.31 (d, J＝8.2 Hz, 1H), 6.98 (d, J＝6.3 Hz, 2H), 5.59 (s, 1H), 3.89 (s, 6H), 2.32 (d, J＝6.8 Hz, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.07, 158.01, 151.55, 149.10, 148.06, 144.58, 138.75, 138.41, 130.89, 128.91, 127.26, 125.51, 121.15, 119.27, 81.96, 53.68, 19.57, 19.42; HRMS (ESI) calcd for C₂₀H₂₁ClN₅O₂ (M+H)⁺ 398.1378, found 398.1379.

  2-(2'-((4''-溴-苯基)(3''-氯-吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-18):收率72%. m.p. 206.8~207.4 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.57 (d, J＝4.9 Hz, 0.5H), 8.29~8.20 (m, 1H), 7.93 (s, 0.5H), 7.69 (d, J＝8.2 Hz, 1H), 7.48~7.30 (m, 3H), 7.28~7.10 (m, 2H), 5.56 (d, J＝6.7 Hz, 1H), 3.84 (d, J＝2.1 Hz, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.12, 158.09, 157.85, 153.17, 151.74, 151.23, 149.30, 147.31, 142.86, 142.67, 142.38, 134.57, 133.26, 131.38, 130.01, 129.88, 128.73, 128.26, 127.82, 124.51, 123.79, 123.56, 121.80, 120.94, 119.05, 82.49, 82.15, 53.77, 53.74; HRMS (ESI) calcd for C₁₈H₁₆BrCl- N₅O₂ (M+H)⁺ 448.0170, found 448.0169.

  2-(2'-((4''-苯基-苯基)(3''-氯-吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-19):收率91%. m.p. 188.8~190.4 ℃; ¹H NMR (300 MHz, CDCl₃) δ 8.51 (s, 1H), 8.37 (d, J＝5.3 Hz, 1H), 7.86 (d, J＝8.2 Hz, 2H), 7.72 – 7.68 (m, 2H), 7.55 (dt, J＝14.3, 4.5 Hz, 4H), 7.48 – 7.44 (m, 1H), 7.40 (d, J＝8.3 Hz, 2H), 5.67 (s, 1H), 3.95 (s, 6H).¹³C NMR (75 MHz, CDCl₃) δ: 172.15, 158.00, 151.69, 149.26, 147.81, 143.90, 142.84, 139.38, 128.76, 128.75, 128.59, 128.54, 128.46, 127.86, 126.88, 126.83, 126.65, 121.14, 119.31, 82.20, 53.77; HRMS (ESI) calcd for C₂₄H₂₁ClN₅O₂ (M+H)⁺ 446.1378, found 446.1380.

  2-(2'-((3''-硝基-4''-甲基-苯基)(3''-氯-吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-20):收率68%. m.p. 197.2~198 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.38 (d, J＝8.7 Hz, 1H), 8.31 (dd, J＝5.2, 3.2 Hz, 1H), 7.90 (dd, J＝15.9, 1.8 Hz, 1H), 7.81 (d, J＝8.2 Hz, 1H), 7.61 (d, J＝7.9 Hz, 1H), 7.54~7.44 (m, 1H), 7.44~7.37 (m, 1H), 7.36 (d, J＝0.9 Hz, 1H), 5.64 (d, J＝4.4 Hz, 1H), 3.89 (m, 7.5H), 2.69 (s, 1.5H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.09, 157.75, 157.66, 151.91, 151.80, 149.91, 149.52, 149.40, 146.94, 146.51, 141.08, 139.70, 135.69, 134.63, 133.74, 133.27, 132.80, 130.03, 129.05, 125.76, 124.64, 120.81, 120.66, 118.96, 118.83, 82.93, 82.62, 53.86, 53.83, 20.1; HRMS (ESI) calcd for C₁₉H₁₈ClN₆O₄ (M+H)⁺ 429.1073, found 429.1072.

  2-(2'-((4''-叔丁基-苯基)(3''-氯-吡啶-4''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-21):收率88%. m.p. 199.1~200.7 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.42 (s, 1H), 8.34~8.27 (m, 1H), 7.64~7.57 (m, 2H), 7.52~7.43 (m, 2H), 7.23~7.17 (m, 2H), 5.62 (s, 1H), 3.92 (s, 6H), 1.39 (s, 9H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.20, 158.04, 153.21, 151.57, 149.16, 148.03, 144.36, 127.95, 126.77, 126.74, 121.15, 119.36, 81.80, 53.77, 34.65, 30.88; HRMS (ESI) calcd for C₂₂H₂₅ClN₅O₂ (M+H)⁺ 426.1691, found 426.1693.

  2-(2'-((4''-甲基-苯基)(4''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-22):收率64%. m.p. 191.2~192 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.50 (d, J＝2.3 Hz, 1H), 8.36 (s, 1H), 7.98 (dd, J＝8.4, 2.5 Hz, 1H), 7.38 (d, J＝7.9 Hz, 2H), 7.30~7.24 (m, 1H), 7.19 (d, J＝8.0 Hz, 2H), 5.58 (s, 1H), 3.89 (s, 6H), 2.44 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.09, 158.26, 150.86, 148.12, 144.55, 139.98, 136.29, 132.48, 130.41, 128.05, 127.22, 123.39, 81.57, 53.61, 21.10; HRMS (ESI) calcd for C₁₉H₁₉ClN₅O₂ (M+H)⁺ 384.1222, found 384.1221.

  2-(2'-((2, 4''-二甲基-苯基)(4''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-23):收率65%. m.p. 189.4~190.8 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.42 (d, J＝2.0 Hz, 1H), 8.11 (s, 1H), 7.93 (dd, J＝8.4, 2.5 Hz, 1H), 7.23 (dd, J＝8.4, 0.5 Hz, 1H), 7.18~7.10 (m, 2H), 6.99 (d, J＝7.7 Hz, 1H), 5.54 (s, 1H), 3.85 (s, 6H), 2.35 (s, 3H), 2.05 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.12, 158.25, 150.87, 147.73, 144.64, 139.99, 136.11, 135.80, 131.95, 131.83, 128.07, 127.77, 126.64, 123.53, 81.48, 53.64, 53.57, 20.97, 18.85; HRMS (ESI) calcd for C₂₀H₂₁ClN₅O₂ (M+H)⁺ 398.1378, found 398.1380.

  2-(2'-((4''-溴-苯基)(4''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-24):收率89%. m.p. 177.7~178.5 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.46 (dd, J＝2.5, 0.5 Hz, 1H), 8.24 (s, 1H), 7.94 (dd, J＝8.4, 2.5 Hz, 1H), 7.73 (d, J＝8.4 Hz, 2H), 7.31~7.24 (m, 1H), 7.23~7.16 (m, 2H), 5.60 (s, 1H), 3.89 (s, 7H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.08, 158.09, 151.18, 147.90, 142.93, 136.09, 133.17, 131.91, 131.32, 129.94, 129.14, 127.91, 124.35, 123.54, 81.99, 53.71; HRMS (ESI) calcd for C₁₈H₁₆BrClN₅O₂ (M+H)⁺ 448.0170, found 448.0172.

  2-(2'-((4''-(对溴苯基)-苯基)(4''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-25):收率66%. m.p. 230.4~231.2 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.43 (d, J＝2.3 Hz, 1H), 8.10 (s, 1H), 7.69 (dd, J＝8.2, 2.3 Hz, 1H), 7.66~7.51 (m, 7H), 7.45 (d, J＝8.6 Hz, 2H), 5.63 (s, 1H), 3.93 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.09, 158.20, 152.69, 149.51, 143.04, 140.45, 139.28, 138.78, 135.94, 131.65, 128.22, 127.06, 126.72, 126.57, 125.28, 121.67, 81.97, 53.75; HRMS (ESI) calcd for C₂₄H₂₀Br- ClN₅O₂ (M+H)⁺ 524.0483, found 524.0484.

  2-(2'-((3, 5''-二氯-苯基)(4''-氯-吡啶-3''-基)-亚甲基)-肼基)-4, 6-二甲氧基嘧啶(Ⅲ-26), 收率61%. m.p. 192.4~193.8 ℃; ¹H NMR (300 MHz, CDCl₃) δ: 8.44~8.39 (m, 1H), 8.10 (s, 1H), 7.94 (dd, J＝8.4, 2.5 Hz, 1H), 7.63 (d, J＝1.9 Hz, 1H), 7.48 (dd, J＝8.2, 2.0 Hz, 1H), 7.30 (dd, J＝8.4, 0.6 Hz, 1H), 7.23 (d, J＝8.2 Hz, 1H), 5.62 (s, 1H), 3.89 (d, J＝10.2 Hz, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 172.10, 157.98, 151.22, 147.38, 140.06, 137.06, 135.62, 134.08, 130.98, 130.69, 128.57, 127.84, 123.72, 82.13, 53.78; HRMS (ESI) calcd for C₁₈H₁₅Cl₃N₅O₂ (M+H)⁺ 438.0286, found 438.0288.

  辅助材料(Supporting Information)  26个芳基吡啶酮腙类化合物对番茄晚疫病菌初筛图片、化合物Ⅲ-3和Ⅲ-14对番茄晚疫病菌精密毒力抑菌图片.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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• 

  图 1  代表性1-芳基-1-吡啶基医药和农药品种

  Figure 1  Representative 1-aryl-1-pyridine based medicine and pesticide varieties

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  图 2  吡啶二芳酮类分子插件及其应用

  Figure 2  Aplication examples of arylpyridinylmethanone plug-in molecules

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  图式 1  目标化合物的合成

  Scheme 1  Synthesis of target compounds

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  表 1  目标化合物结构及收率

  Table 1.  Structure and yield of target compounds

  Compd.	R1	R2	Yield/%
  Ⅲ-1	Ph	Ph	75
  Ⅲ-2	4-tBuC6H4	4-NO2C6H4	82
  Ⅲ-3	CH3	2-CH3C6H4	67
  Ⅲ-4	4-tBuC6H4	3-Pyridyl	88
  Ⅲ-5	3, 4-Cl2C6H3	3-Pyridyl	62
  Ⅲ-6	4-CH3C6H4	4-Pyridyl	90
  Ⅲ-7	4-iPrC6H4	4-Pyridyl	68
  Ⅲ-8	3, 4-(CH3)2C6H3	4-Pyridyl	65
  Ⅲ-9	2-CH3-3-ClC6H3	4-Pyridyl	70
  Ⅲ-10	4-BrC6H4	4-Pyridyl	61
  Ⅲ-11	4-BrC6H4	2-Cl-3-pyridyl	63
  Ⅲ-12	4-tBuC6H4	2-Cl-3-pyridyl	56
  Ⅲ-13	4-CH3C6H4	2-Cl-3-pyridyl	55
  Ⅲ-14	3, 4-Cl2C6H3	2-Cl-3-pyridyl	64
  Ⅲ-15	2, 4-(CH3)2C6H3	3-Cl-4-pyridyl	91
  Ⅲ-16	4-CH3C6H4	3-Cl-4-pyridyl	93
  Ⅲ-17	3, 4-(CH3)2C6H3	3-Cl-4-pyridyl	78
  Ⅲ-18	4-BrC6H4	3-Cl-4-pyridyl	72
  Ⅲ-19	4-PhC6H4	3-Cl-4-pyridyl	91
  Ⅲ-20	3-NO2-4-CH3C6H3	3-Cl-4-pyridyl	68
  Ⅲ-21	4-tBuC6H4	3-Cl-4-pyridyl	88
  Ⅲ-22	4-CH3C6H4	4-Cl-3-pyridyl	64
  Ⅲ-23	2, 4-(CH3)2C6H3	4-Cl-3-pyridyl	65
  Ⅲ-24	4-BrC6H4	4-Cl-3-pyridyl	89
  Ⅲ-25	4-(4ꞌ-Br-C6H4)C6H4	4-Cl-3-pyridyl	66
  Ⅲ-26	3, 5-Cl2C6H3	4-Cl-3-pyridyl	61

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  表 2  目标化合物Ⅲ-1~Ⅲ-26的抑菌活性(抑制率/%)^a

  Table 2.  Antifungal activity of title compounds Ⅲ-1~Ⅲ-26 (inhibitory rate/%)

  Compd.	RC	PC	BC	PI	TC	FS	SS	ET
  嘧菌腙	32.76	55.19	69.74	34.62	52.31	8.48	98.30	90.80
  Ⅲ-1	19.38	51.75	42.92	62.50	25.46	38.45	52.45	89.68
  Ⅲ-2	0	2.26	8.80	4.43	0	19.98	11.34	46.17
  Ⅲ-3	20.29	42.75	84.86	65.23	41.48	33.06	100	91.66
  Ⅲ-4	43.51	14.33	24.68	45.51	32.41	30.61	8.30	0
  Ⅲ-5	0	26.69	38.82	61.01	39.41	44.61	33.22	57.97
  Ⅲ-6	17.94	25.41	32.19	40.17	29.40	35.92	25.76	81.49
  Ⅲ-7	20.62	17.77	35.62	36.97	13.89	26.23	10.97	84.52
  Ⅲ-8	31.13	37.96	57.51	57.69	42.13	46.29	27.95	84.07
  Ⅲ-9	29.69	41.41	66.09	55.98	43.98	49.05	25.76	91.25
  Ⅲ-10	28.04	27.13	61.80	55.98	26.39	37.76	43.96	84.19
  Ⅲ-11	25.77	46.82	74.68	65.17	38.89	37.07	74.28	89.01
  Ⅲ-12	20.21	39.44	66.09	53.63	29.63	42.14	60.94	80.71
  Ⅲ-13	0	38.46	51.69	40.74	42.17	40.23	68.60	68.40
  Ⅲ-14	1.48	42.53	47.62	66.08	27.19	34.48	65.89	75.93
  Ⅲ-15	3.09	3.00	6.87	0.21	6.02	5.49	11.45	1.30
  Ⅲ-16	17.53	5.71	33.48	50.85	8.33	8.71	32.31	5.79
  Ⅲ-17	0	14.70	51.01	44.33	13.83	29.83	53.20	20.52
  Ⅲ-18	0	17.64	43.79	50.46	68.91	30.10	50.77	22.57
  Ⅲ-19	0	9.05	15.57	11.82	8.30	15.87	17.28	86.87
  Ⅲ-20	0	7.46	32.05	46.66	6.91	28.19	36.46	75.24
  Ⅲ-21	0	2.71	20.31	6.54	1.15	17.51	27.55	20.52
  Ⅲ-22	16.91	26.88	57.08	47.01	19.91	27.39	53.42	91.48
  Ⅲ-23	0	38.91	45.37	57.63	16.36	26.54	48.34	47.88
  Ⅲ-24	0	12.67	36.11	52.99	18.90	32.56	52.39	0
  Ⅲ-25	0	0	7.00	6.76	0	1.37	43.75	86.19
  Ⅲ-26	0	22.85	34.31	34.20	13.83	29.28	45.10	62.07
  a c＝0.07 mmol•L-1.

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  表 3  部分化合物的EC₅₀

  Table 3.  EC₅₀ of part title compounds

  病原菌	化合物	EC50/(μmol•L-1)	R2	毒力回归方程
  SS	嘧菌腙	52.29±1.54	0.999	y＝1.19x-0.78
  	Ⅲ-3	36.39±6.68	0.938	y＝2.13x-2.77
  	Ⅲ-11	60.27±5.74	0.979	y＝1.62x-2.9
  	Ⅲ-14	67.96±5.81	0.992	y＝0.78x-1.43
  	Ⅲ-18	＞140
  PC	嘧菌腙	48.11±4.99	0.940	y＝1.19x-2.05
  	Ⅲ-3	99.04±5.64	0.999	y＝1.09x-2.18
  	Ⅲ-11	110.97±5.01	0.984	y＝1.24x-2.53
  	Ⅲ-14	＞140
  	Ⅲ-18	＞140
  PI	嘧菌腙	96.99±9.06	0.999	y＝2.44x-4.85
  	Ⅲ-3	55.96±7.57	0.992	y＝2.04x-3.53
  	Ⅲ-11	74.71±3.77	0.970	y＝0.92x-1.73
  	Ⅲ-14	61.33±2.00	0.935	y＝0.53x-0.96
  	Ⅲ-18	99.81±10.74	0.971	y＝0.75x-1.5
  BC	嘧菌腙	31.38±1.83	0.821	y＝1.53x-2.26
  	Ⅲ-3	22.18±6.03	0.953	y＝1.51x-1.96
  	Ⅲ-11	＞140
  	Ⅲ-14	＞140
  	Ⅲ-18	＞140
  TC	嘧菌腙	93.33±9.41	0.998	y＝2.2x-4.33
  	Ⅲ-3	＞140
  	Ⅲ-11	＞140
  	Ⅲ-14	＞140
  	Ⅲ-18	＜0.35	0.998	y＝0.11x+0.18

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•