diethyl 1-(4-methoxylphenyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate | 83300-82-7

• 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-(4-methoxylphenyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: diethyl 1,4-dihydro-1-(4-methoxyphenyl)-4-phenylpyridine-3,5-dicarboxylate；diethyl N-(4-methoxyphenyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate；diethyl 1-(4-methoxyphenyl)-4-phenyl-4H-pyridine-3,5-dicarboxylate
• CAS: 83300-82-7
• 化学式: C₂₄H₂₅NO₅
• 分子量: 407.466
• InChiKey: VIRJKNQQIURAIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl 1-(4-methoxylphenyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate 以 四氢呋喃 、 甲醇 为溶剂， 以68.1%的产率得到tetraethyl 3,9-di(4-methoxylphenyl)-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：

  4-methoxy-N-[(E)-phenylmethylidene]aniline 、 丙炔酸乙酯 在 scandium tris(trifluoromethanesulfonate) 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以75%的产率得到diethyl 1-(4-methoxylphenyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Catalytic synthesis of 1,4-dihydropyridine derivatives using scandium(III) triflate

  摘要：

  Scandium(III) triflate smoothly catalyzed the reaction of imines with ethyl propiolate (2.5 equiv) to produce the corresponding N-substituted 1,4-dihydropyridines in good yields in toluene or BTF under reflux conditions. It also catalyzed the reaction of aniline and ethyl propiolate (3.2 equiv) to give another 1,4-dihydropyridine bearing three ester groups in moderate yield under the same conditions. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2007.11.003

文献信息

• Dually Acting Nonclassical 1,4-Dihydropyridines Promote the Anti-Tuberculosis (Tb) Activities of Clofazimine
  作者：Fabian Lentz、Norbert Reiling、Gabriella Spengler、Annamária Kincses、Andrea Csonka、Joseph Molnár、Andreas Hilgeroth

  DOI：10.3390/molecules24162873

  日期：——

  identified. As related classical 1,4-dihydropyridines are known as inhibitors of the transmembrane efflux pump ABCB1 in cancer cells, we wondered whether a use of our compounds may be of favour to enhance the antituberculotic drug efficacy of the second-line antituberculotic drug clofazimine, which is a known substrate of ABCB1 by a suggested inhibition of a corresponding efflux pump in Mycobacterium

  在标准治疗中，有效抗结核药物的数量被严格限制为四种一线药物。在耐药的情况下，使用二线抗生素的疗效和耐受性较差。因此，迫切需要新型抗结核药物。我们合成了新型的非经典 1,4-二氢吡啶，并根据取代基效应评估了它们的抗结核特性。可以确定优选的取代基。由于相关的经典 1,4-二氢吡啶被称为癌细胞中跨膜外排泵 ABCB1 的抑制剂，我们想知道使用我们的化合物是否有利于增强二线抗结核药物氯法齐明的抗结核药物疗效，它是 ABCB1 的已知底物，建议抑制结核分枝杆菌 (Mtb) 中相应的外排泵。为此，我们确定了我们的化合物在小鼠 T 淋巴瘤细胞系模型中的 ABCB1 抑制特性，然后在我们的 Mtb 菌株中与氯法齐明共同应用中评估了所选化合物的药物增强特性。我们确定了新的氯法齐明毒性增强剂，可以防止由外排泵活性介导的氯法齐明耐药性的发展。
• 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。
• Effect of substituents in the dihydropyridine ring on the reactivity of the ester group of 3,5-dialkoxycarbonyl-1,4-dihydropyridines
  作者：B. S. Chekavichus、A. �. Sausin'、G. Ya. Dubur

  DOI：10.1007/bf00506586

  日期：1982.8
• 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.
• Montmorillonite K-10 catalyzed green synthesis of 2,6-unsubstituted dihydropyridines as potential inhibitors of PDE4
  作者：T. Ram Reddy、G. Rajeshwar Reddy、L. Srinivasula Reddy、Chandana Lakshmi T. Meda、Kishore V.L. Parsa、K. Shiva Kumar、Y. Lingappa、Manojit Pal

  DOI：10.1016/j.ejmech.2012.12.052

  日期：2013.4

  Montmorillonite K-10 mediated MCR of anilines, arylaldehydes and ethyl-3,3-diethoxypropionate in water afforded 2,6-unsubstituted dihydropyridines depending on the nature of anilines employed. A variety of dihydropyridines were prepared by using this green methodology in good yields and montmorillonite K-10 was found to be an inexpensive and reusable catalyst. The structure elaboration of a representative compound was carried out under Heck conditions. Some of the compounds synthesized showed significant inhibition of PDE4B when tested in vitro. Docking studies indicated that one of the ester moieties of these compounds played a key role in their interactions with the PDE4B protein. (C) 2013 Elsevier Masson SAS. All rights reserved.