(4-oxo-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-3-yl)acetic acid ethyl ester | 40277-49-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4-oxo-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-3-yl)acetic acid ethyl ester
• 英文别名: ethyl 2-(4-oxo-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-3(4H)-yl)acetate；ethyl (4-oxo-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-3(4H)-yl)acetate；ethyl 2-(4-oxo-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-3-yl)acetate
• CAS: 40277-49-4
• 化学式: C₁₄H₁₆N₂O₃S
• mdl: MFCD02363398
• 分子量: 292.359
• InChiKey: ABRJMUYLUUBNTB-UHFFFAOYSA-N

物化性质

• 熔点：
  106-108 °C
• 沸点：
  495.1±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  87.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-oxo-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-3-yl)acetic acid ethyl ester 在 一水合肼 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 9.0h， 生成 2-(2-(4-oxo-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-3(4H)-yl)acetyl)-N-phenylhydrazine-1-carbothioamide
  参考文献：
  名称：

  基于 Ethyl 2-Amino-4,5,6,7-Tetra Hydrobenzo[b]Thiophene-3-Carboxylate 的新型乳腺癌细胞凋亡诱导剂的发现：合成、体外和体内活性评估

  摘要：

  采用多组分合成方法合成了 2-氨基-4,5,6,7-四氢苯并[b]噻吩-3-羧酸乙酯 1。当氨基酯 1 与异硫氰酸乙酯反应生成苯并[4,5]噻吩并[2,3-d][1,3]thiazin-4-one 3.在DCM和Et3N中用氯乙酰氯酰化氨基酯1，得到酰化酯4。氨基-酯 1 被环化为苯并[4,5]噻吩并[2,3-d]嘧啶-4(3H)-one 8，它与一些烷基化剂反应导致在氮 9-13 处烷基化。酰肼 14 被用作合成子来合成衍生物 15-19。合成氯噻吩并[2,3-d]嘧啶20并与水合肼反应得到肼衍生物21，其用作获得衍生物22-28的支架。亲核取代反应用于从氯噻吩并 [2,3-d] 嘧啶 20 中获得化合物 29-35。 在抗癌疗法开发的过程中，评估了必需化合物在体外对 MCF-7 和 HepG 的细胞毒性-2 癌细胞系。12 种化合物显示出令人感兴趣的抗增殖潜力，IC50 为 23.2 至

  DOI：

  10.3390/molecules25112523
• 作为产物：
  描述：

  2-氨基-3-腈基-4,5,6,7--四氢苯并[B]噻吩 在 硫酸 、 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 10.0h， 生成 (4-oxo-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-3-yl)acetic acid ethyl ester
  参考文献：
  名称：

  1,2,3-三唑标记的噻吩并[2,3-d]嘧啶酮衍生物的合成，抗菌活性和对接研究

  摘要：

  新型（1-（取代苯基）-1 H -1,2,3-三唑-4-基）甲基-2-（4-氧代-5,6,7,8-四氢苯并[1,2]噻吩并[2合成了，3 - d ]嘧啶-3（4 H）-基）乙酸酯衍生物。所有化合物对革兰氏阴性菌（大肠杆菌和肺炎克雷伯菌）和革兰氏阳性菌（枯草芽孢杆菌和蜡状芽孢杆菌）均显示出显着的抗菌活性。特别是，（1-（3-硝基苯基）-1 H -1,2,3-三唑-4-基）甲基-2-（4-氧代-5,6,7,8-四氢苯并[1，2]噻吩发现[2,3 - d ]嘧啶-3（4 H）-基）乙酸酯对大肠杆菌最有效，MIC 25μg/ ml的肺炎克雷伯菌和枯草芽孢杆菌。分子对接也在枯草芽孢杆菌的嘌呤核糖开关和大肠杆菌的硫胺素焦磷酸核糖开关上进行。

  DOI：

  10.1002/jhet.2995

文献信息

• A facile synthesis of some novel fused [1,2,4]triazolo[3,4-b][1,3,4]thiadiazol derivatives
  作者：Kerru Nagaraju、Yalagala Kotaiah、Chinnam Sampath、Nallapaneni Harikrishna、Chunduri Venkata Rao

  DOI：10.1080/17415993.2012.734306

  日期：2013.6.1

  A series of novel 3-[6-(4-substituted phenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one derivatives (7a–7h) have been synthesized from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (1) through a multi-step reaction sequence. The key intermediate (6) on condensation with various substituted aromatic carboxylic acids in

  一系列新型3-[6-(4-取代苯基)-[1,2,4]三唑并[3,4-b][1,3,4]噻二唑-3-基甲基]-5,6,7 ,8-四氢[1]苯并噻吩并[2,3-d]嘧啶-4(3H)-one衍生物(7a-7h)由2-氨基-4,5,6,7-四氢苯并[b]噻吩合成-3-腈 (1) 通过多步反应序列。关键中间体 (6) 在磷酰氯存在下与各种取代的芳族羧酸缩合得到一系列标题化合物 (7a-7h)。所有新合成化合物的结构均基于其 IR、1H-NMR、13C-NMR 和液相色谱质谱数据。
• Synthesis and Antioxidant Activity of 1,2,4-Triazole linked Thieno[2,3- d]pyrimidine Derivatives
  作者：Suresh Maddila、Avula S. Kumar、Sridevi Gorle、M. Singh、Palakondu Lavanya、S.B. Jonnalagadda

  DOI：10.2174/157018013804725152

  日期：2012.12.1

  A series of Schiff bases derivatives novel 3-(4-substitutedbenzylideneamino-5-mercapto-4H-[1,2,4]triazol-3- ylmethyl)-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one derivatives (7a–k) have been synthesized from compound (1) through a multi step reaction. The key intermediate (6) on condensation with various suitable aldehydes in the presence of sulfuric acid afforded a series of title compounds (7a–k). The structures of all newly synthesized compounds were established on the basis of their elemental analysis, IR, 1H-NMR, 13C-NMR and MS spectral data. All these novel compounds were screened for their in vitro antioxidant activity by employing DPPH, hydrogen peroxide, and nitric oxide radical scavenging assays. The compounds 7c, 7j, 7k, 7e and 7b showed significant radical savenging due to the presence of electron-withdrawing groups.

  从化合物(1)出发，通过多步反应合成了一系列新型的希夫碱衍生物，即3-(4-取代苄亚胺氨基-5-巯基-4H-[1,2,4]三唑-3-基甲基)-5,6,7,8-四氢-3H-苯并[4,5]噻吩[2,3-d]嘧啶-4-酮衍生物(7a–k)。在硫酸存在下，关键中间体(6)与各种合适的醛缩合，得到了一系列标题化合物(7a–k)。所有新合成的化合物的结构均基于其元素分析、IR、1H-NMR、13C-NMR和MS光谱数据确定。所有这些新型化合物均通过DPPH、过氧化氢和一氧化氮自由基清除实验进行了体外抗氧化活性筛选。化合物7c、7j、7k、7e和7b显示出显著的自由基清除能力，这归因于存在吸电子基团。
• Design, synthesis, and biological evaluation of thienopyrimidine and thienotriazine derivatives as multitarget anti‐Alzheimer agents
  作者：Kholoud I. Eissa、Mona M. Kamel、Lamia W. Mohamed、Mai A. Galal、Asmaa E. Kassab

  DOI：10.1002/ddr.21968

  日期：2022.9

  The 12 newly synthesized compounds were screened for their inhibition activity against acetylcholinesterase enzyme (AChE). Compounds that exerted the most potent AChE inhibitory action were further evaluated for their BChE inhibitory activity. In addition, the inhibitory effects of all newly synthesized compounds on Aβ and reactive oxygen species were assessed. Compounds 4d, 10b, and 10c showed potent

  设计并合成了一系列结合多奈哌齐分子药效团的四氢苯并噻吩并嘧啶和四氢苯并噻吩三嗪。筛选了 12 种新合成的化合物对乙酰胆碱酯酶 (AChE) 的抑制活性。进一步评估了发挥最有效 AChE 抑制作用的化合物的 BChE 抑制活性。此外，评估了所有新合成的化合物对 A β和活性氧的抑制作用。化合物4d、10b和10c显示出与多奈哌齐相当的对AChE的有效抑制活性。化合物10b (IC 50 = 0.124 ± 0.006 nM) 显示出最大的 AChE 抑制作用和最有效的 BChE 抑制作用 (IC 50  = 0.379 ± 0.02 nM)。这三种化合物对Aβ积累的抑制作用比多奈哌齐更强。此外，它们显示出强大的抗氧化活性。化合物4d和10b与 AChE 活性位点的结合模式使其显着的 AChE 抑制活性合理化。总之，这些结果表明这些衍生物可能是用于阿尔茨海默病管理的有前途的多功能药物。
• Synthesis and anti-tumor activities of N′-benzylidene-2-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazone derivatives
  作者：Jiangping Lou、Zhen Liu、Yan Li、Mi Zhou、Zhengxi Zhang、Shu Zheng、Renxiao Wang、Jian Li

  DOI：10.1016/j.bmcl.2011.09.061

  日期：2011.11

  A compound with a cyclic thienopyrimidine moiety and an aceto-hydrazone moiety in its chemical structure was discovered in a cell-based screening to have noticeable cytotoxicity on several tumor cell lines. A total of 38 derivatives of this compound were synthesized at five steps with high yields. These compounds were tested in standard MTT assays, and several compounds exhibited improved cytotoxic activities. The most potent compounds have IC50 values of 10-20 mu M on A549, HeLa, and MBA-MD-231 tumor cells. Flow cytometry analysis of several active compounds and subsequent examination of caspase activation indicate that they induce caspase-dependent apoptosis in tumor cells. In addition, these compounds do not have obvious effect on a normal cell line HEK-293T, demonstrating the desired selectivity against tumor cells. Results from a fluorescence polarization-based in vitro binding assay indicate that this class of compounds does not significantly interrupt the interactions between Mcl-1 and Bid. Their cytotoxicity is achieved presumably through other mechanisms. (C) 2011 Elsevier Ltd. All rights reserved.
• Bohm; Muller; Pech, Pharmazie, 1986, vol. 41, # 9, p. 661 - 661
  作者：Bohm、Muller、Pech

  DOI：——

  日期：——