4-chloro-7,9-dimethyl-pyrido[3',2':4,5]thieno[3,2-d]pyrimidine | 67795-48-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 4-chloro-7,9-dimethyl-pyrido[3',2':4,5]thieno[3,2-d]pyrimidine
• 英文别名: 4-Chloro-7,9-dimethylpyrido[3',2':4,5]thieno[3,2-d]pyrimidine；6-chloro-11,13-dimethyl-8-thia-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene
• CAS: 67795-48-6
• 化学式: C₁₁H₈ClN₃S
• mdl: MFCD00830462
• 分子量: 249.724
• InChiKey: CQRSHGSHXMCUTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-7,9-dimethyl-pyrido[3',2':4,5]thieno[3,2-d]pyrimidine 在 氨 作用下， 生成 7,9-Dimethylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine
  参考文献：
  名称：

  Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors

  摘要：

  Cdc7 kinase plays a critical role in the regulation of DNA replication in eukaryotic cells and has been proposed as a target for cancer therapy. We have identified a class of Cdc7/Dbf4 inhibitors with a pyrido-thieno-pyrimidine core structure. Synthesis of a focused pyrido-thieno-pyrimidine library yielded potent and selective Cdc7 inhibitors with antiproliferative activity against cancer cells in vitro. Their synthesis and SAR data are presented herein. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.093
• 作为产物：
  描述：

  3-氨基-4,6-二甲基噻吩并[2,3-b]吡啶-2-羧酸乙酯 在 三氯氧磷 作用下， 以 formamide 为溶剂， 反应 27.0h， 生成 4-chloro-7,9-dimethyl-pyrido[3',2':4,5]thieno[3,2-d]pyrimidine
  参考文献：
  名称：

  结构不同的三环 M4 正变构调节剂 (PAM) 化学型的发现——第 2 部分

  摘要：

  这封信详细介绍了我们为开发具有改进的药理特性的新型三环 M 4 PAM 支架所做的努力。这项努力涉及一种“回接”策略，以取代 3-amino-4,6-dimethylthieno[2,3- b ]pyridine-2-carboxamide 核心，从而发现了两个新的三环核心：7,9 -二甲基吡啶并[3',2':4,5]噻吩并[3,2-d]嘧啶核和2,4-二甲基噻吩并[2,3 - b :5,4-c']联吡啶核。两个三环核心都显示出对人类 M 4受体的低纳摩尔效力。

  DOI：

  10.1016/j.bmcl.2021.128416

文献信息

• Discovery of Potent Antiproliferative Agents Targeting EGFR Tyrosine Kinase Based on the Pyrido[3′,2′:4,5]thieno[3,2-<i>d</i>]pyrimidin-4-amine Scaffold
  作者：Yasmine Mohamed Abdel Aziz、Mohamed Mokhtar Said、Hosam Ahmed El Shihawy、Mai Fathy Tolba、Khaled Abouzid Mohamed Abouzid

  DOI：10.1248/cpb.c15-00592

  日期：——

  A series of pyridothieno[3,2-d]pyrimidin-4-amines was designed and synthesized as congeners to the classical 4-anilinoquinazolines as ATP-competitive epidermal growth factor receptor (EGFR) inhibitors. Compound 5a exhibited the most potent and selective inhibitory activity against EGFR with an IC50 value of 36.7 nM. Moreover, compounds 4b and 5a showed remarkable cell growth inhibition against leukemia, central nervous system cancer, and non-small cell lung cancer cell lines that overexpress EGFR, with growth inhibition of 50% (GI50) values of around 10 nM in the full U.S. National Cancer Institute 60 cell panel assay. Cell cycle studies indicated that compounds 4b and 5a induced significant cell cycle arrest in the S-phase and G0/G1, respectively, in addition to boosting P27kip expression. Compound 5a did not alter the viability of placental trophoblasts, which reflects its safety for normal cells. The standard COMPARE analyses demonstrated considerable correlation levels between compounds 4b and 5a and erlotinib, with pyridinium chlorochromate (PCC) values of 0.707 and 0.727, respectively.

  研究人员设计并合成了一系列吡啶噻吩并[3,2-d]嘧啶-4-胺，作为经典 4-苯胺基喹唑类化合物的同系物，作为 ATP 竞争性表皮生长因子受体（EGFR）抑制剂。化合物 5a 对表皮生长因子受体具有最强的选择性抑制活性，其 IC50 值为 36.7 nM。此外，化合物 4b 和 5a 对过量表达表皮生长因子受体的白血病、中枢神经系统癌症和非小细胞肺癌细胞系表现出显著的细胞生长抑制作用，在全套美国国家癌症研究所 60 细胞面板检测中，生长抑制 50%（GI50）值约为 10 nM。细胞周期研究表明，化合物 4b 和 5a 除了促进 P27kip 的表达外，还分别诱导细胞周期明显停滞在 S 期和 G0/G1。化合物 5a 没有改变胎盘滋养细胞的活力，这反映了它对正常细胞的安全性。标准 COMPARE 分析表明，化合物 4b 和 5a 与厄洛替尼之间具有相当高的相关性，吡啶氯铬酸盐 (PCC) 值分别为 0.707 和 0.727。
• Fused pyridothienopyrimidine heterocycles. 2*. A facile and efficient synthesis of the annelated pyrido[3′,2′:4,5]thieno-[2,3-e]pyrimido[3,2-c]pyrimidones
  作者：F. A. El-Essawy

  DOI：10.1007/s10593-009-0351-2

  日期：2009.7

  The cyclocondensation reactions of 4-aminopyridothienopyrimidine with malonates and their acetylation were studied. All structures were determined by 1H NMR and mass spectra techniques.

  研究了4-氨基吡啶并噻吩并嘧啶与丙二酸酯的环缩合反应及其乙酰化反应。所有结构均通过1 H NMR和质谱技术确定。
• Tornetta,B. et al., Gazzetta Chimica Italiana, 1978, vol. 108, p. 57 - 62
  作者：Tornetta,B. et al.

  DOI：——

  日期：——
• Research on thienopyridines and pyridothienopyrimidines. 3. Transformations 0f 7,9-dimethyl-8-nitropyrido[3',2'?4,5]-thieno [3,2-d]pyrimidin-4-ones
  作者：V. I. Shvedov、T. P. Sycheva、T. V. Sakovich

  DOI：10.1007/bf00471902

  日期：1979.10
• Vieweg; Bohm; Krasselt, Pharmazie, 1992, vol. 47, # 10, p. 751 - 754
  作者：Vieweg、Bohm、Krasselt、Leistner、Wagner

  DOI：——

  日期：——