diethyl 1-phenyl-4-(4-methoxylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate | 915910-86-0

• 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-(4-methoxylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: diethyl 4-(4-methoxylphenyl)-1-phenyl-1,4-dihydropyridine-3,5-dicarboxylate；diethyl 4-(4-methoxyphenyl)-1-phenyl-1,4-dihydropyridine-3,5-dicarboxylate；diethyl 4-(4-methoxyphenyl)-1-phenyl-4H-pyridine-3,5-dicarboxylate
• CAS: 915910-86-0
• 化学式: C₂₄H₂₅NO₅
• 分子量: 407.466
• InChiKey: AWGLUTNWYNMEAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.19
• 重原子数：
  30.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.07
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  diethyl 1-phenyl-4-(4-methoxylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate 以 四氢呋喃 、 甲醇 为溶剂， 以62.7%的产率得到tetraethyl 3,9-diphenyl-6,12-di(4-methoxylphenyl)-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：

  4-甲氧基苯甲醛 、 苯胺 、 丙炔酸乙酯 在 溶剂黄146 作用下， 生成 diethyl 1-phenyl-4-(4-methoxylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  发现具有抗分枝杆菌活性双重模式的新型N-苯基1,4-二氢吡啶。

  摘要：

  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。

  DOI：

  10.1016/j.bmcl.2016.11.010

文献信息

• 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。
• 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。
• Manipulating [2 + 2] photodimerization of 1,4-dihydropyridines within γ -cyclodextrin
  作者：Wuji Sun、Qiangwen Fan、Hong Yan

  DOI：10.1016/j.jphotochem.2018.03.046

  日期：2018.5

  volume in γ-CD is responsible for the observed selectivity. The formation of 1:2 host-guest inclusion complex plays an important role in this reaction, and manipulates DHPs to perform [2 + 2] photodimerization as expected. In order to investigate the inclusion process, the spectral characteristics were investigated and the theoretical study was performed using density functional theory (DFT).

  在γ-环糊精（γ -CD）存在下照射1,4-二氢吡啶（DHP）可以在中压汞灯下有效形成笼状二聚体。γ -CD中复合的DHP的笼二聚体产率可达到约80％，远高于非复合状态的DHP 。假设可用的腔体体积为γ-CD负责观察到的选择性。1：2宿主-客体包含复合物的形成在此反应中起重要作用，并按预期操作DHP进行[2 + 2]光二聚。为了研究包含过程，研究了光谱特征，并使用密度泛函理论（DFT）进行了理论研究。
• Biological evaluation of 4-aryl-1,4-dihydropyridines as VEGFR-2 kinase inhibitors
  作者：W. Sun、Z. Ma、H. Yan

  DOI：10.1134/s1070363216120574

  日期：2016.12

  Vascular endothelial growth factor-2 receptor (VEGFR-2) kinase is a promising target for the development of novel anticancer drugs. Molecular docking modeling was performed on a series of 4-aryl-1,4-dihydropyridines derivatives to evaluate the structural basis for VEGFR-2 inhibitory activity. Some 4-aryl-1,4-dihydropyridines were synthesized in the reaction of aromatic aldehydes and ethyl propiolate with anilines in acetic acid. The biological activities were evaluated against the cells A549, A431 and Hep-G2. The results indicated that 4-aryl-1,4-dihydropyridines could be the promising potential VEGFR-2 inhibitors.