CN114195725A - 一种含有三氮唑的查尔酮类化合物及其应用 - Google Patents
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- 229940124350 antibacterial drug Drugs 0.000 claims abstract description 4
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- 230000005764 inhibitory process Effects 0.000 abstract description 8
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- 241000894006 Bacteria Species 0.000 abstract description 2
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- 238000012216 screening Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
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- 239000003814 drug Substances 0.000 description 7
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Abstract
本发明公开了一种含有三氮唑的查尔酮类化合物及其应用。该化合物的结构式如下式所示：
通式Ⅰ其中，R1:4‑H,4‑F,4‑Cl,4‑Br,4‑Me,4‑OMe,4‑Ph,2,4‑F2,2,4‑Cl2 
实验证实，通式Ⅰ所示的化合物对细菌，尤其是对金黄色葡萄球菌具有优异的抑制作用，抑菌圈直径高于阳性对照盐酸环丙沙星，为临床抗菌药物的筛选提供了新的选择。
Description
技术领域
本发明涉及一种查尔酮类化合物，特别涉及含有三氮唑的查尔酮类化合物及其抑菌活性的应用，属于合成药物技术领域。
背景技术
金黄色葡萄球菌是医院和社区环境中最常见的病原体之一，与多种临床
重要感染有关，是公共健康的常见威胁。因于长期和过量使用抗生素，金黄色葡萄球菌的耐药性问题日趋严重，已成为严重威胁全球的主要医疗问题之一（T. Horino.; S.Hori. Metastatic infection during Staphylococcus aureus bacteremia. J. Infect. Chemother. 2020, 26 (2), 162-169；S. Gatadi.; J. Gour.; S. Nanduri.Natural product derived promising anti-MRSA drug leads: A review. Bioorg. Med. Chem. 2019, 27, 3760-3774.）。目前临床上对其治疗的选择很有限（ H. L. Qin.; J. Liu.; W.Y. Fang.; L.Ravindar.; K.P. Rakesh. Indole-based derivatives as potential antibacterialactivity against methicillin-resistance Staphylococcus aureus (MRSA). Eur. J. Med. Chem. 2020, 194, 112245；Y. G. Cong.; S.J. Yang.; X.C. Rao. Vancomycinresistant Staphylococcus aureus infections: a review of case updating andclinical features. J. Adv. Res. 2020,21, 169-176）；这就迫切需要开发新型抗菌剂。
发明内容
本发明的目的在于提供一种含有三氮唑的查尔酮类化合物。
本发明的另一目的是提供一种含有三氮唑的查尔酮类化合物的抑菌活性在抗菌药物中的应用。
为实现本发明的目的，本发明采用如下技术方案：
本发明提供的含有三氮唑的查尔酮类化合物的结构式如通式Ⅰ所示：
通式Ⅰ如下：
通式Ⅰ
R1: 4-H, 4-F, 4-Cl, 4-Br, 4-Me, 4-OMe, 4-Ph, 2,4-F2, 2,4-Cl2
也就是，R1可以是4-H，4-F，4-Cl，4-Br，4-Me，4-OMe，4-Ph，2,4-F2，2,4-Cl2中的任意一个；R2可以是1H-1,2,4-三氮唑， 1H-1,2,3-三氮唑，2H-1,2,3-三氮唑中的任意一个。
本发明提供的如通式Ⅰ所示的化合物的抑菌应用实验如下：
将样品用DMSO配成溶液后加到滤纸片上，每片含药量为200 µg。将
滤纸片分别贴于涂布了细菌（大肠杆菌、金黄色葡萄球菌）的固体平板上，于孵化箱内37 ℃培养24-36 h，记录实验结果，以盐酸环丙沙星作为阳性对照，以抑菌圈直径（单位：mm）的大小表示样品抑菌活性的大小，实验重复三次，抑菌结果取其平均值。
通过以上实验证实本发明的如通式Ⅰ所示化合物对金黄色葡萄球菌具有很强的抑菌活性，抑制作用超过了阳性对照，可用于抗菌药物的制备。
本发明取得的有益效果是：
本发明的如通式Ⅰ所示化合物对金黄色葡萄球菌具有优异的抑制作用，
预示其具有很好的药用前景，有可能成为临床使用的新型抑菌药物。
附图说明
图1为1-(4-氟苯基)-2-(1H-1,2,3-三氮唑甲基)-2-丙烯-1-酮的1H NMR图。
图2为1-(4-氟苯基)-2-(1H-1,2,3-三氮唑甲基)-2-丙烯-1-酮的13C NMR图。
图3为1-(4-氯苯基)-2-(1H-1,2,4-三氮唑甲基)-2-丙烯-1-酮的1H NMR图。
图4为1-(4-氯苯基)-2-(1H-1,2,4-三氮唑甲基)-2-丙烯-1-酮的13C NMR图。
图5为1-(4-氟苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮的1H NMR图。
图6为1-(4-氟苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮的13C NMR图。
具体实施方式
以下实施例用于说明本发明。
实施例1
1-(4-氟苯基)-2-(1H-1,2,3-三氮唑甲基)-2-丙烯-1-酮及其抑菌应用
（1）结构确证
1-(4-氟苯基)-2-(1H-1,2,3-三氮唑甲基)-2-丙烯-1-酮，分子量为231，分子式为C12H10N3OF，白色固体。1-(4-氟苯基)-2-(1H-1,2,3-三氮唑甲基)-2-丙烯-1-酮的结构是基于它的核磁图谱、质谱和元素分析等数据确认的。
质谱数据：ESI -MS m/z：232.2 [M+H]+，254.1 [M+Na]+。
元素分析数据：Anal. calcd for C12H10N3OF：C 62.33，H 4.36，N 18.17；found C62.15，H 4.80，N 18.48。
（2）抑菌应用
将1-(4-氟苯基)-2-(1H-1,2,3-三氮唑甲基)-2-丙烯-1-酮用DMSO配成溶液后加到滤纸片上，每片含药量为200 µg。将滤纸片贴于涂布了金黄色葡萄球菌的固体平板上，于孵化箱内37 ℃培养24-36 h后，测量其抑菌圈直径，实验重复三次，三次的抑菌圈直径分别为25.0mm, 25.0mm, 26.0mm，平均值为25.3 mm，高于阳性对照盐酸环丙沙星（21.6 mm）。
实施例2
1-(4-氯苯基)-2-(1H-1,2,4-三氮唑甲基)-2-丙烯-1-酮及其抑菌应用
（1）结构确证
1-(4-氯苯基)-2-(1H-1,2,4-三氮唑甲基)-2-丙烯-1-酮，分子量为247.5，分子式为C12H10N3OCl，白色固体。1-(4-氯苯基)-2-(1H-1,2,4-三氮唑甲基)-2-丙烯-1-酮的结构是基于它的核磁图谱、质谱和元素分析等数据确认的。
质谱数据：ESI -MS m/z：248.1 [M+H]+，270.1 [M+Na]+。
元素分析数据：Anal. calcd for C12H10N3OCl：C 58.19， H 4.07，N 16.97；foundC 58.45，H 4.46，N 17.08。
（2）抑菌应用
将1-(4-氯苯基)-2-(1H-1,2,4-三氮唑甲基)-2-丙烯-1-酮用DMSO配成溶液后加到滤纸片上，每片含药量为200 µg。将滤纸片贴于涂布了金黄色葡萄球菌的固体平板上，于孵化箱内37 ℃培养24-36 h后，测量其抑菌圈直径，实验重复三次，三次的抑菌圈直径分别为24.0mm, 25.5mm, 25.0mm，平均值为24.8 mm，高于阳性对照盐酸环丙沙星（21.6 mm）。
实施例3
1-(4-氟苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮及其抑菌应用
（1）结构确证
1-(4-氟苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮，分子量为231，分子式为C12H10N3OF，白色固体。1-(4-氟苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮的结构是基于它的核磁图谱、质谱和元素分析等数据确认的。
质谱数据：ESI -MS m/z：232.2 [M+H]+，254.2 [M+Na]+。
元素分析数据： Anal. calcd for C12H10N3OF：C 62.33，H 4.36，N 18.17；found C62.59，H 4.75，N 18.54
（2）抑菌应用
将1-(4-氟苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮用DMSO配成溶液后加到滤纸片上，每片含药量为200 µg。将滤纸片贴于涂布了金黄色葡萄球菌的固体平板上，于孵化箱内37 ℃培养24-36 h后，测量其抑菌圈直径，实验重复三次，三次的抑菌圈直径分别为24.0mm, 23.0mm, 21.5mm,平均值为22.8 mm，高于阳性对照盐酸环丙沙星（21.6 mm）。
需要说明，目前，本发明的技术方案已经进行了小规模中试，并在小范围内开展了用户使用调研，调研结果表明用户满意度较高。现在已开始着手准备产品正式投产，进行产业化应用，同时进行了知识产权风险预警调研。
Claims (7)
1.一种含有三氮唑的查尔酮类化合物，其特征在于结构式如通式Ⅰ所示：
通式Ⅰ。
2.根据权利要求1所述的一种含有三氮唑的查尔酮类化合物，其特征在于是：1-(4-氟苯基)-2-(1H-1,2,3-三氮唑甲基)-2-丙烯-1-酮。
3.根据权利要求1所述的一种含有三氮唑的查尔酮类化合物，其特征在于是：1-(4-氯苯基)-2-(1H-1,2,4-三氮唑甲基)-2-丙烯-1-酮。
4.根据权利要求1所述的一种含有三氮唑的查尔酮类化合物，其特征在于是：1-(4-氟苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮。
5.根据权利要求1所述的一种含有三氮唑的查尔酮类化合物，其特征在于是：1-(4-甲基苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮。
6.根据权利要求1所述的一种含有三氮唑的查尔酮类化合物，其特征在于是：1-(4-甲氧基苯基)-2-(2H-1,2,3-三氮唑甲基)-2-丙烯-1-酮。
7.一种如权利要求1所述的含有三氮唑的查尔酮类化合物的应用，其特征在于用于抗菌药物的应用。
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| MASARU OGATA 等: "Synthesis and Antifungal Activity of a Series of Novel 1, 2-Disubstituted Propenones", J. MED. CHEM., vol. 30, no. 8, pages 1497 - 1502 * |
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