2-甲基-6-(4-甲基苯基)烟酸乙酯 | 271597-75-2

• 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
• 中文名称: 2-甲基-6-(4-甲基苯基)烟酸乙酯
• 英文名称: ethyl 2-methyl-6-(4-tolyl)pyridine-3-carboxylate
• 英文别名: Ethyl 2-methyl-6-p-tolylpyridine-3-carboxylate；ethyl 2-methyl-6-(4-methylphenyl)pyridine-3-carboxylate
• CAS: 271597-75-2
• 化学式: C₁₆H₁₇NO₂
• 分子量: 255.316
• InChiKey: OAEOOOKZIMODSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-甲基-6-(4-甲基苯基)烟酸乙酯 在 一水合肼 作用下， 反应 3.0h， 以78%的产率得到2-methyl-6-(4-tolyl)nicotinohydrazide
  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
• 作为产物：
  描述：

  1-(4-甲基苯基)-2-丙炔-1-醇 在 manganese(IV) oxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-甲基-6-(4-甲基苯基)烟酸乙酯
  参考文献：
  名称：

  Total Synthesis of the Thiopeptide Promothiocin A

  摘要：

  The thiopeptide (or thiostrepton) antibiotics are a class of sulfur-containing highly modified cyclic peptides with interesting biological activity. Described herein is the total synthesis of the thiopeptide antibiotic promothiocin A, which utilizes a modified Bohlmann-Rahtz pyridine synthesis to establish the oxazolyl-thiazole-pyridine heterocyclic centerpiece of the antibiotic. The oxazole building blocks were obtained by a dirhodium(II)-catalyzed chemoselective carbenoid N-H insertion reaction followed by cyclodehydration, and the thiazoles by the Hantzsch reaction. Two different strategies for macrocyclization were successfully employed, with the dehydroalanine side chain of the natural product being introduced in the last steps of the synthesis.

  DOI：

  10.1021/ja994247b

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。
• Consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz syntheses of tri- and tetrasubstituted pyridines
  作者：Janis Dohe、Thomas J.J. Müller

  DOI：10.1515/znb-2016-0046

  日期：2016.6.1

  The concatenation of the modified Sonogashira alkynone synthesis and the Bagley-Bohlmann-Rahtz pyridine synthesis gives novel consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz (cBBR) syntheses of tri- and tetrasubstituted pyridines in a one-pot fashion. With these processes 15 differently substituted 3-ethoxycarbonyl 2-methylpyridines can be readily obtained in modest to moderate yields.

  修改后的Sonogashira炔酮合成与Bagley-Bohlmann-Rahtz吡啶合成的串联反应，以一锅法给出了新颖的连续三元和四元组分偶联-Bagley-Bohlmann-Rahtz (cBBR)合成方法，用于合成三取代和四取代吡啶。通过这些过程，可以轻松地以适度到中等产率获得15种不同取代的3-乙氧羰基-2-甲基吡啶。

• Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity
  作者：Hatem A. Abdel-Aziz、Tarek Aboul-Fadl、Abdul-Rahman M. Al-Obaid、Mohamed Ghazzali、Abdullah Al-Dhfyan、Alessandro Contini

  DOI：10.1007/s12272-012-0904-2

  日期：2012.9

  Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines. Variable cell growth inhibitory activities were obtained with IC50 range from 24.99 to 66.78 μM where the compound 6c exhibited the maximum activity. Structure activity relationship analysis has been performed and a common pharmacophore model for the synthesized derivatives has been obtained by using the pharmacophore elucidation module of the software MOE. The best model obtained is characterized by two projected locations of potential H-bond donors (F 3 and F4) and two Aromatic annotations (F1 and F2).

  合成了新型6-芳基-2-甲基 nicotine 酸肼（4a-c）及其对应的肼酮（5a-c和6a-i）。对6h的X射线单晶衍射确认了肼酮6a-i的化学结构。合成化合物的抗增殖活性在K562白血病细胞系上进行了研究，获得了不同的细胞生长抑制活性，IC50范围为24.99至66.78μM，其中化合物6c表现出最大的活性。进行了结构活性关系分析，并利用软件MOE的药效团阐明模块获得了合成衍生物的共同药效团模型。获得的最佳模型具有两个潜在H键供体的投影位置（F3和F4）和两个芳香标记（F1和F2）。
• Enaminones in heterocyclic synthesis: A new regioselective synthesis of 2,3,6‐trisubstituted pyridines, 6‐substituted‐3‐aroylpyridines and 1,3,5‐triaroylbenzenes
  作者：Balkis Al‐Saleh、Mervat Mohammed Abdelkhalik、Afaf Mohammed Eltoukhy、Mohammed Hilmy Elnagdi

  DOI：10.1002/jhet.5570390528

  日期：2002.9

  1-Substituted-3-dimethylaminopropenones 1a-d reacted with acetylacetone and with ethyl acetoacetate to yield regioselectively 2,3,6-trisubstituted pyridines. Refluxing 1a-d in acetic acid/ammonium acetate resulted in the formation of 6-substituted-3-aroylpyridines, whereas refluxing in acetic acid alone afforded 1,3,5-triaroylbenzene.

  1-取代的3-二甲基氨基丙烯酮1a-d与乙酰丙酮和乙酰乙酸乙酯反应以产生区域选择性的2,3,6-三取代的吡啶。在乙酸/乙酸铵中回流1a-d导致形成6-取代的3-芳酰基吡啶，而仅在乙酸中回流则得到1,3,5-三芳酰基苯。
• 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。