ethyl 6-(3,4-dimethoxyphenyl)-2-methylnicotinate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 6-(3,4-dimethoxyphenyl)-2-methylnicotinate
• 英文别名: Ethyl 6-(3,4-dimethoxyphenyl)-2-methylpyridine-3-carboxylate
• 化学式: C₁₇H₁₉NO₄
• 分子量: 301.342
• InChiKey: JLSQVYNUCQHECT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  57.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 6-(3,4-dimethoxyphenyl)-2-methylnicotinate 在 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 5-amino-1-(6-(3,4-dimethoxyphenyl)-2-methylnicotinoyl)-1H-pyrazole-4-carbonitrile
  参考文献：
  名称：

  某些新型吡唑啉-噻唑杂化物的合成及其抗菌活性

  摘要：

  通过硫代酰胺衍生物5a，b与1-芳基-2-溴代乙炔6a-d，氯丙酮8a-c和酰氯的反应合成了一系列新型的噻唑基吡唑啉7a-h，9a-f和11a-f 10a-c。此外，从烯胺酮13开始制备吡唑15a-c和20。筛选这些新合成的化合物对四种细菌的体外抗菌活性。化合物11b对肺炎克雷伯菌显示中等活性。化合物7c和11c揭示了对铜绿假单胞菌的中等活性。另外，确定了新合成的化合物对五种真菌菌株的抗真菌活性。化合物7e，7g和11e对黄曲霉和扩展青霉表现出良好的活性。

  DOI：

  10.1002/jhet.3698
• 作为产物：
  描述：

  3,4-二甲氧基苯乙酮 在 ammonium acetate 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 溶剂黄146 为溶剂， 反应 13.0h， 生成 ethyl 6-(3,4-dimethoxyphenyl)-2-methylnicotinate
  参考文献：
  名称：

  Design, Synthesis and Antitubercular Activity of Certain Nicotinic Acid Hydrazides

  摘要：

  合成了三系列6-芳基-2-甲基烟碱酰肼4a–i、N'-芳亚甲基-6-(4-溴苯基)-2-甲基烟碱酰肼7a–f和N'-(未/取代的2-氧代吲哚啉-3-亚甲基)-6-(4-氟苯基)-2-甲基烟碱酰肼8a–c，并评估了它们对结核杆菌的体外抗菌活性。结果显示，靛红酰肼8a–c相较于母体酰肼4c活性显著更高。酰肼8b和8c在所有测试化合物中显示出最高的活性（MIC分别为12.5和6.25 µg/mL）。化合物8b和8c对HT-29、PC-3、A549、HepG2和MCF-7癌细胞系也无明显细胞毒性。此外，8b和8c显示出良好的类药性得分，分别为0.62和0.41。这两个靛红酰肼为未来开发更强效的抗结核药物提供了极佳的基础。SAR研究表明，合成衍生物的亲脂性是影响其抗结核活性的关键因素。最后，建立了理论动力学研究来预测活性衍生物的ADME。

  DOI：

  10.3390/molecules20058800

文献信息

• Design, Synthesis and Antitubercular Activity of Certain Nicotinic Acid Hydrazides
  作者：Wagdy Eldehna、Mohamed Fares、Marwa Abdel-Aziz、Hatem Abdel-Aziz

  DOI：10.3390/molecules20058800

  日期：——

  Three series of 6-aryl-2-methylnicotinohydrazides 4a–i, N′-arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a–f, and N′-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a–c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M. tuberculosis. The results showed that isatin hydrazides 8a–c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 µg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.

  合成了三系列6-芳基-2-甲基烟碱酰肼4a–i、N'-芳亚甲基-6-(4-溴苯基)-2-甲基烟碱酰肼7a–f和N'-(未/取代的2-氧代吲哚啉-3-亚甲基)-6-(4-氟苯基)-2-甲基烟碱酰肼8a–c，并评估了它们对结核杆菌的体外抗菌活性。结果显示，靛红酰肼8a–c相较于母体酰肼4c活性显著更高。酰肼8b和8c在所有测试化合物中显示出最高的活性（MIC分别为12.5和6.25 µg/mL）。化合物8b和8c对HT-29、PC-3、A549、HepG2和MCF-7癌细胞系也无明显细胞毒性。此外，8b和8c显示出良好的类药性得分，分别为0.62和0.41。这两个靛红酰肼为未来开发更强效的抗结核药物提供了极佳的基础。SAR研究表明，合成衍生物的亲脂性是影响其抗结核活性的关键因素。最后，建立了理论动力学研究来预测活性衍生物的ADME。
• Synthesis, in vitro biological evaluation and in silico studies of certain arylnicotinic acids conjugated with aryl (thio)semicarbazides as a novel class of anti-leishmanial agents
  作者：Wagdy M. Eldehna、Hadia Almahli、Tamer M. Ibrahim、Mohamed Fares、Tarfah Al-Warhi、Frank M. Boeckler、Adnan A. Bekhit、Hatem A. Abdel-Aziz

  DOI：10.1016/j.ejmech.2019.06.051

  日期：2019.10

  Herein we introduce new compounds as conjugates of arylnicotinic acids with aryl (thio)semicarbazide derivatives. Based on a structure-guided approach, they were designed to possess anti-leishmanial activity through anti-folate mechanism, via targeting Leishmania major pteridine reductase 1 (Lm-PTR1). The in vitro anti-promastigote and anti-amastigote activity were promising for many thiosemicarbazide

  在这里，我们介绍新的化合物，作为芳基烟酸与芳基（硫代）氨基脲衍生物的共轭物。基于结构指导的方法，它们被设计成通过靶向利什曼原虫主要蝶啶还原酶1（Lm -PTR1）的抗叶酸机制而具有抗利什曼病的活性。对于许多硫代氨基脲衍生物，其体外抗前鞭毛体和抗鞭毛体的活性是有希望的，并且优于参比米替福星。与参比miltefosine（IC 50）相比，活性最高的化合物8i和8j表现出其抗鞭毛的活性，IC 50值分别为4.2和3.3μM。值7.3）。它们的抗叶酸机制是通过叶酸和亚叶酸逆转这些化合物的抗Leishmanial活性的能力来证实的，与Lm -PTR1抑制剂甲氧苄啶相当。有趣的是，最活性化合物的体外细胞毒性试验显示出比米替福辛更高的选择性指数，强调了它们对哺乳动物细胞的安全性。此外，以Lm -PTR1作为推定目标的对接实验使体外抗利什曼原虫活性合理化。将在硅片预测显示最具活性的化合物具有良好的药代动
• Pyridine-Ureas as Potential Anticancer Agents: Synthesis and In Vitro Biological Evaluation
  作者：Mohamed El-Naggar、Hadia Almahli、Hany Ibrahim、Wagdy Eldehna、Hatem Abdel-Aziz

  DOI：10.3390/molecules23061459

  日期：——

  reference drug doxorubicin (IC50 = 1.93 µM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l⁻n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer

  为了开发有效的抗癌剂，合成了一系列新的吡啶-脲8a⁻n。在体外评估所有新制备的衍生物对乳腺癌MCF-7细胞系增殖的生长抑制活性。与参考药物阿霉素相比，发现化合物8e和8n是针对MCF-7细胞最活跃的同类物（治疗48小时后IC50分别为0.22和1.88 µM；治疗72小时后分别为0.11和0.80 µM），并具有增强的活性。 IC50 = 1.93 µM）。此外，根据US-NCI方案评估了八个选定的吡啶8b，8d，8e，8i，8j和8ln的体外抗癌活性。在NCI分析中，吡啶8b和8e被证明是最有效的抗癌药，平均抑制率分别为43％和49％。8b和8e均显示出对所有受测试癌细胞系的所有亚组生长抑制的抗增殖活性（GI对于8b； 12％至78％； GI对于8e； 15％至91％）。体外筛选吡啶8b和8e对VEGFR-2的抑制活性。两种化合物均以微摩尔IC50值5.0±1.91和3.93±0.73
• Domino synthesis of functionalized pyridine carboxylates under gallium catalysis: Unravelling the reaction pathway and the role of the nitrogen source counter anion
  作者：Dinesh Kumar、Himanshu Sharma、Nirjhar Saha、Asit K. Chakraborti

  DOI：10.1002/asia.202200304

  日期：2022.8

  domino Michael-cyclodehydration-aromatization multicomponent reaction for the synthesis of functionalized pyridines from enaminones, 1,3-diketones, and NH4OAc under solvent-free condition is reported. The method is simple, high-yielding, and operates under mild conditions with a wide substrate scope. The use of different ammonium salts as a nitrogen source was investigated and the decisive role of the acetate

  报道了在无溶剂条件下由烯胺酮、1,3-二酮和 NH 4 OAc 合成官能化吡啶的 GaI 3催化多米诺迈克尔环脱水芳构化多组分反应。该方法简单、收率高、操作条件温和、底物范围广。研究了使用不同的铵盐作为氮源，并确定了醋酸盐抗衡阴离子的决定性作用。
• Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase
  作者：Chang-bo Deng、Juan Li、Lu-yi Li、Feng-jie Sun

  DOI：10.1016/j.bmcl.2016.04.031

  日期：2016.7

  In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50 = 19.4 +/- 2.5 mu M). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury. (C) 2016 Elsevier Ltd. All rights reserved.