diethyl 1-phenyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate | 83300-81-6

• 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: diethyl 1-phenyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: diethyl 1,4-diphenyl-1,4-dihydropyridine-3,5-dicarboxylate；MC2734；diethyl 1,4-diphenyl-4H-pyridine-3,5-dicarboxylate
• CAS: 83300-81-6
• 化学式: C₂₃H₂₃NO₄
• 分子量: 377.44
• InChiKey: WFUYARDFDRGYFM-UHFFFAOYSA-N

物化性质

• 熔点：
  143-145 °C(Solv: cyclohexane (110-82-7); benzene (71-43-2))
• 沸点：
  497.8±45.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl 1-phenyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate 以 四氢呋喃 、 甲醇 为溶剂， 以62.3%的产率得到tetraethyl 3,9-diphenyl-6,12-diphenyl-3,9-diazapentacyclo[6.4.0.0^2,7.0^4,11.0^5,10]dodecane-1,5,7,11-tetracarboxylate
  参考文献：
  名称：

  Design, Synthesis and Biological Evaluation of 3,9-diazatetraasteranes as Novel Matrilysin Inhibitors

  摘要：

  Matrilysin is an ideal biological target to develop novel inhibitors because it is overexpressed in malignant tumour cells. A series of 3,9‐diazatetraasteranes was designed as inhibitors of matrilysin, which was an ideal biological target because it is responsible for aggressive malignant phenotypes and poor prognoses implicated in many cancers. Docking simulation supported the initial pharmacophore hypothesis and suggested a common interaction mechanism of 3,9‐diazatetraasteranes with the catalytic site of matrilysin. The 3,9‐diazatetraasteranes were synthesized by the photocyclization of 4‐aryl‐1,4‐dihydropyridines, and their structures were determined using 1H NMR, 13C NMR and MS. The inhibitory activities of these compounds on matrilysin were investigated in vitro using an MTT assay in A549 (small cell lung cancer) cells. The results show that the 3,9‐diazatetraasteranes can inhibit the growth of A549 tumour cells. The best IC50 value is approximately 50 μm. This result indicates that 3,9‐diazatetraasteranes will be useful pharmacological tools for the investigation of matrilysin inhibitors.

  DOI：

  10.1111/cbdd.12185
• 作为产物：
  描述：

  苯甲醛 在 3,3',5,5'-四叔丁基-4,4'-联苯醌 、 BF₄^(1-)*C₁₈H₁₄Cl₂N₃O⁽¹⁺⁾ 、 N,N-二异丙基乙胺 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 反应 75.0h， 生成 diethyl 1-phenyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  NHC催化氧化1,4-二氢吡啶的对映选择性脱对称

  摘要：

  N-杂环卡宾在氧化条件下催化的前手性二醛前所未有的去对称化反应，被用于从3,5-二碳醛底物开始的高对映选择性合成1,4-二氢吡啶（DHP）。所得5-甲酰基-1,4-DHP-3-羧酸酯的合成精制可使用一类药学上相关的1,4-DHP-3,5-二羧酸酯（Hantzsch酯）。DFT计算表明，该过程的对映选择性取决于过渡态，该过渡态涉及外部醌氧化剂对Breslow中间体的氧化。

  DOI：

  10.1002/chem.201901243

文献信息

• Studies on chemoselective synthesis of 1,4- and 1,2-dihydropyridine derivatives by a Hantzsch-like reaction: a combined experimental and DFT study
  作者：Peng Li、Shijie Wang、Nana Tian、Hong Yan、Juan Wang、Xiuqing Song

  DOI：10.1039/d0ob02289f

  日期：——

  propiolate as raw materials. The mechanisms for the formation of 1,4-DHP and 1,2-DHP were proposed based on the isolated intermediate named diethyl 4-((phenylamino)methylene)pent-2-enedioate generated by the Michael addition of aniline and ethyl propiolate. The transition state structures were optimized and the reaction energy barriers of intermediates in the speculated mechanisms were calculated by DFT

  在通过类 Hantzsch 反应制备 3,5-二羧酸二乙酯-1,4-二氢吡啶 (1,4-DHP) 的实验过程中，发现副产物 3,5-二羧酸二乙酯-1，反应生成2-二氢吡啶(1,2-DHP)。为探讨这一现象，以芳香胺、芳香醛和丙炔酸乙酯为原料，研究了反应条件对1,4-DHP和1,2-DHP收率的影响。1,4-DHP 和 1,2-DHP 的形成机理基于苯胺和丙炔酸乙酯的迈克尔加成生成的名为 4-((苯基氨基)亚甲基)戊二烯二酸二乙酯的分离中间体提出。在M062X/def2TZVP//B3LYP-D3/def-SVP水平上，通过DFT计算，优化了过渡态结构，并计算了推测机理中中间体的反应能垒。发现中间体的反应能垒和主要构型IM2和IM3'是化学选择性的决定因素。总之，这些结果表明，通过类 Hantzsch 反应合成 1,4-DHP 和 1,2-DHP 具有高化学选择性，并且在不同条件下可以很容易地获得
• Multicomponent Reactions for Diverse Synthesis of<i>N</i>-Substituted and NH 1,4-Dihydropyridines
  作者：Jieping Wan、Youyi Zhou、Yunyun Liu、Zheng Fang、Chengping Wen

  DOI：10.1002/cjoc.201300918

  日期：2014.3

  The multicomponent reactions of aldehydes, electron deficient alkynes and amines have been successfully performed to yield a number of symmetrical 2,6‐unsubstituted 1,4‐dihydropyridines (1,4‐DHPs). This method has been found generally applicable for the synthesis of both N‐substituted and N‐unsubstituted 1,4‐DHPs by employing secondary amine to activate the alkyne component via enaminoester intermediates

  醛，缺乏电子的炔烃和胺的多组分反应已成功进行，得到了许多对称的2,6-未取代的1,4-二氢吡啶（1,4-DHPs）。已经发现该方法通常可用于合成N-取代的和N-未取代的1,4-DHP，方法是使用仲胺通过烯胺酯中间体活化炔烃组分。本方法通过烯胺型活化进行，这不同于采用AcOH作为溶剂的已知方法。
• Study of 1,4-Dihydropyridine Structural Scaffold: Discovery of Novel Sirtuin Activators and Inhibitors
  作者：Antonello Mai、Sergio Valente、Sarah Meade、Vincenzo Carafa、Maria Tardugno、Angela Nebbioso、Andrea Galmozzi、Nico Mitro、Emma De Fabiani、Lucia Altucci、Aleksey Kazantsev

  DOI：10.1021/jm9008289

  日期：2009.9.10

  deacetylases have emerged as potential therapeutic targets for treatment of human illnesses such as cancer, metabolic, cardiovascular, and neurodegenerative diseases. The benefits of sirtuin modulation by small molecules have been demonstrated for these diseases. In contrast to the discovery of inhibitors of SIRT1, -2, and -3, only activators for SIRT1 are known. Here, we rationalized the potential of

  NAD +依赖的沉默调节蛋白脱乙酰基酶已经成为治疗人类疾病如癌症，代谢，心血管和神经退行性疾病的潜在治疗靶标。对于这些疾病，已经证明了通过小分子调节瑟土因的益处。与SIRT1，-2和-3抑制剂的发现相反，仅SIRT1的激活剂是已知的。在这里，我们在合理化显影沉默调节蛋白的配体的前所未见的二氢吡啶骨架的电位，因此，我们制备了一系列1,4-二氢吡啶基衍生物的1 - 3。对它们的SIRT1-3脱乙酰基酶活性的评估表明，二氢吡啶结构的N1位上的取代基对Sirtuin活性的重要性。环丙基，苯基或苯乙基位于N1处赋予了非选择性SIRT1和SIRT2抑制活性，而苄基位于N1处赋予了有效的SIRT1，-2和-3激活。用小鼠C2C12成肌细胞进行的hMSC和线粒体功能研究进行的衰老分析证实了该化合物的新颖独特的SIRT激活特性。
• Hetero-intermolecular [2+2] photocycloaddition of 1,4-dihydropyridines: a combined experimental and DFT study
  作者：Qiangwen Fan、Hongbo Tan、Peng Li、Hong Yan

  DOI：10.1039/c8nj02192a

  日期：——

  In this article, the hetero-intermolecular [2+2] photocycloaddition of 1,4-dihydropyridines (1,4-DHPs) in solution was reported, wherein head-to-tail (HT) dimeric products (syn-dimers and cage dimers) were formed exclusively through successive inter- and intra-molecular [2+2] cycloaddition. The effects of irradiation wavelength, solvents and substituents on the efficiency of these transformations were

  在本文中，在异质的分子间[2 + 2]的溶液中1,4-二氢吡啶（1,4-DHP类）光环被报道，其特征在于，头-尾（HT）的二聚产物（顺式-dimers和笼二聚体）仅通过连续的分子间和分子内[2 + 2]环加成反应形成。研究了辐照波长，溶剂和取代基对这些转化效率的影响。为了阐明光环加成反应的内在特征和立体选择性，进行了DFT和TDDFT理论计算，以揭示详细的反应过程。
• Discovery of novel N- phenyl 1,4-dihydropyridines with a dual mode of antimycobacterial activity
  作者：Fabian Lentz、Marc Hemmer、Norbert Reiling、Andreas Hilgeroth

  DOI：10.1016/j.bmcl.2016.11.010

  日期：2016.12

  There is an urgent need for novel drugs for the treatment of tuberculosis (TB) due to the increasing prevalence of antibiotic resistance among Mycobacterium tuberculosis (Mtb) strains against first-line and second-line therapeutics. We developed novel N-phenyl 1,4-dihydropyridines as potential antituberculotic agents. The observed activity depends on the substitution patterns of the aromatic residues

  由于结核分枝杆菌（Mtb）菌株对一线和二线治疗剂的耐药性日益增加，因此迫切需要用于治疗结核病（TB）的新药。我们开发了新型的N-苯基1,4-二氢吡啶类化合物作为潜在的抗结核药。观察到的活性取决于芳族残基的取代方式。N-未取代的1,4-二氢吡啶是已知的与癌症相关的跨膜外排泵ABCB1的抑制剂。基于与1,4-二氢吡啶结合和MTb外排泵Rv0194相关的ABCB1氨基酸序列的相似性，我们在细胞系模型中确定了我们化合物的ABCB1抑制特性。我们鉴定了一种化合物，该化合物实质上增加了两种抗结核药物（ABCB1的底物）的活性。