ethyl 4-(4-fluorophenyl)-6-phenyl-2-thioxo-3,4-dihydro-1H-pyrimidine-5-carboxylate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl 4-(4-fluorophenyl)-6-phenyl-2-thioxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• 英文别名: ethyl 4-(4-fluorophenyl)-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；Ethyl 6-(4-fluorophenyl)-4-phenyl-2-sulfanyl-1,6-dihydropyrimidine-5-carboxylate；ethyl 4-(4-fluorophenyl)-6-phenyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylate
• 化学式: C₁₉H₁₇FN₂O₂S
• 分子量: 356.421
• InChiKey: CLTRMVFYUSNGOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-fluorophenyl)-6-phenyl-2-thioxo-3,4-dihydro-1H-pyrimidine-5-carboxylate 在 potassium carbonate 、 lithium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (Z)-4-[4-[[5-ethoxycarbonyl-4-(4-fluorophenyl)-6-phenyl-pyrimidin-2-yl]sulfanylmethyl]phenyl]-2-hydroxy-4-oxo-but-2-enoic acid
  参考文献：
  名称：

  Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase

  摘要：

  The synthesis and antiviral evaluation of a series of dihydropyrimidinone and thiopyrimidine derivatives bearing aryl alpha, gamma-diketobutanoic acid moiety are described using the Biginelli multicomponent reaction as key step. The most active among 20 synthesized novel compounds were 4c, 4d and 5b, which possess nanomolar HIV-1 integrase (IN) stand transfer (ST) inhibition activities. In order to understand their mode of interactions within the IN active site, we docked all the compounds into the previously reported X-ray crystal structure of IN. We observed that compounds 4c, 4d and 5b occupied an area close to the two catalytic Mg2+ ions surrounded by their chelating triad (E221, D128 and D185), DC16, Y212 and the beta-diketo acid moiety of 4c, 4d and 5b chelating Mg2+. As those compounds lack anti-HIV activities in cell, their prodrugs were synthetized. The prodrug 4c' exhibited an anti-HIV activity of 0.19 mu M in primary human lymphocytes with some cytotoxicity. All together, these results indicate that the new analogs potentially interact within the catalytic site with highly conserved residues important for IN catalytic activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.015
• 作为产物：
  描述：

  对氟苯甲醛 、 苯甲酰乙酸乙酯 、 硫脲 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 ethyl 4-(4-fluorophenyl)-6-phenyl-2-thioxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
  参考文献：
  名称：

  具有抗癌活性的新型融合嘧啶衍生物：合成，拓扑异构酶II抑制，凋亡诱导活性和分子模型研究。

  摘要：

  设计并制备了一系列新的三唑并嘧啶和噻唑并嘧啶氢溴酸盐作为拓扑异构酶II抑制剂。所有合成化合物的筛选均由美国国家癌症研究所（NCI）进行。确定了针对代表不同癌症类型的60种人类癌细胞系的活性。因此，化合物3d是最有效的抑制剂，尤其是针对肾细胞系A498的抑制剂，引起92.46％的抑制（IC 50  = 3.5μM ）。此外，细胞周期分析显示由化合物3d在G2 / M期引起的细胞周期停滞，导致细胞增殖抑制和促凋亡活性。此外，噻唑并嘧啶3d表现出强大的拓扑异构酶II抑制活性（IC 50与用作参比化合物的阿霉素（IC 50 2.67μM ）相比则为2.89μM。此外，进行了合成化合物的分子建模研究，并揭示了化合物3d在拓扑异构酶II酶结合位点的结合相互作用，使该衍生物的显着抑制活性合理化。

  DOI：

  10.1016/j.bioorg.2020.104134

文献信息

• Aerobic copper-promoted oxidative dehydrosulfurative carbon–oxygen cross-coupling of 3,4-dihydropyrimidine-1<i>H</i>-2-thiones with alcohols
  作者：Jihong Lee、Yujeong Kwon、Dong-Chan Lee、Jeong-Hun Sohn

  DOI：10.1039/d1ra07713a

  日期：——

  A wide range of readily available DHPMs and alcohols makes the presented reaction an attractive method to access biologically valuable 2-alkoxypyrimidine derivatives with rapid diversification.

  一系列易得的DHPMs和醇使得所呈现的反应成为一种吸引人的方法，可用于快速多样化地获得具有生物学价值的2-烷氧基嘧啶衍生物。
• Dehydrosulfurative C–N Cross-Coupling and Concomitant Oxidative Dehydrogenation for One-Step Synthesis of 2-Aryl(alkyl)aminopyrimidines from 3,4-Dihydropyrimidin-1<i>H</i>-2-thiones
  作者：Nguyen Huu Trong Phan、Hyeji Kim、Hyunik Shin、Hee-Seung Lee、Jeong-Hun Sohn

  DOI：10.1021/acs.orglett.6b02617

  日期：2016.10.7

  A method for the synthesis of 2-aryl(alkyl)aminopyrimidines from readily available 3,4-dihydropyrimidin-1H-2-thiones (DHPMs) via dehydrosulfurative C–N cross-coupling and concomitant oxidative dehydrogenation under a Pd/Cu catalytic system is described. This reaction protocol provides unprecedented diversity of fully substituted 2-aryl(alkyl)aminopyrimidines in a single step from a wide range of DHPMs

  一种在Pd / Cu催化体系下通过脱硫C–N交叉偶联和伴随的氧化脱氢从容易获得的3,4-二氢嘧啶-1 H -2-硫酮（DHPM）合成2-芳基（烷基）氨基嘧啶的方法描述。该反应方案只需一步即可从多种DHPM和胺偶联伙伴中提供前所未有的完全取代的2-芳基（烷基）氨基嘧啶多样性。
• Dehydrosulfurative arylation with concomitant oxidative dehydrogenation for rapid access to pyrimidine derivatives
  作者：Hyeji Kim、Nguyen Huu Trong Phan、Hyunik Shin、Hee-Seung Lee、Jeong-Hun Sohn

  DOI：10.1016/j.tet.2017.10.010

  日期：2017.11

  This report describes a cascade reaction method for the synthesis of 2-arylpyrimidine derivatives via dehydrosulfurative carbon-carbon cross-coupling and concomitant oxidative dehydrogenation under a Pd/Cu catalytic system. It provides rapid and general access to a diverse range of 2-arylpyrimidines in a single step from a wide range of 3,4-dihydropyrimidin-1H-2-thiones (DHPMs) and arylboronic acids

  该报告描述了在Pd / Cu催化体系下通过脱氢硫化碳-碳交叉偶联和伴随的氧化脱氢合成2-芳基嘧啶衍生物的级联反应方法。它可从一个范围广泛的3,4-二氢嘧啶-1 H -2-硫酮（DHPM）和芳基硼酸一步一步快速，通用地获得各种2-芳基嘧啶。
• Design, synthesis and chemoinformatic studies of new thiazolopyrimidine derivatives as potent anticancer agents via phosphodiesterase-5 inhibition and apoptotic inducing activity
  作者：Mohamed T.M. Nemr、Mohamed Teleb、Asmaa M. AboulMagd、Mostafa E. El-Naggar、Noha Gouda、A.A. Abdel-Ghany、Yaseen A.M.M. Elshaier

  DOI：10.1016/j.molstruc.2022.134216

  日期：2023.1

  respectively in comparison to sildenafil (IC50 0.689 nM). Moreover, compounds 3a, 3c, 3f, 3g, 3h were found to have potent cytotoxic activities against MCF-7 cancer cell line with IC50 ranging from 5.47±0.4 to 9.92±0.9 µM. Apoptosis cytometric assay showed that compound 5a induced pronounced increase in the total percent of apoptotic HCT116 cells (15.87%) compared to 3c (12.43%), mainly during late stage

  抑制磷酸二酯酶 5 (PDE5) 已被证实为可能的癌症新治疗方法。为了进一步探索这一概念，设计并合成了三个系列的含有噻唑并嘧啶的化合物作为 PDE5 抑制剂。除了对三种不同癌细胞系（结肠直肠癌结肠癌；HCT-116，乳腺乳腺癌；MCF-7 和人前列腺癌；PC3）的抗增殖活性外，还评估了所有化合物对 PDE5 的抑制作用。细胞系（人肺成纤维细胞；WI38）。在合成的化合物中，三种化合物（3c、4a 和 5a）显着抑制 PDE5，IC 50分别为 0.046 nM、0.323 nM 和 0.546 nM，与西地那非（IC 500.689 纳米）。此外，化合物3a、3c、3f、3g、3h对 MCF-7 癌细胞系具有有效的细胞毒活性，IC 50范围为 5.47±0.4 至 9.92±0.9 µM。细胞凋亡细胞计数分析表明，与3c (12.43%) 相比，化合物5a诱导的凋亡 HCT116 细胞的总百分比
• Oxidative Dehydrosulfurative Carbon–Oxygen Cross-Coupling of 3,4-Dihydropyrimidine-2-thiones with Aryl Alcohols
  作者：Trong Nguyen Huu Phan、Jihong Lee、Hyunik Shin、Jeong-Hun Sohn

  DOI：10.1021/acs.joc.1c00273

  日期：2021.4.2