4-chloropyrido[3',2':4,5]thieno[3,2-d]pyrimidine | 55115-80-5

• 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-chloropyrido[3',2':4,5]thieno[3,2-d]pyrimidine
• 英文别名: 6-chloro-8-thia-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene
• CAS: 55115-80-5
• 化学式: C₉H₄ClN₃S
• mdl: MFCD01312792
• 分子量: 221.67
• InChiKey: QCUXTBKFKCTJIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  4-chloropyrido[3',2':4,5]thieno[3,2-d]pyrimidine 在 palladium on activated charcoal 氢气 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidine
  参考文献：
  名称：

  吡啶并[3'，2'：4,5]噻吩并[3,2- d ]嘧啶衍生物的合成†

  摘要：

  吡啶并[3'，2'：4,5] thieno [3,2- d ]嘧啶及其衍生物已被合成。

  DOI：

  10.1002/jhet.5570110622
• 作为产物：
  描述：

  3-氨基噻吩并[2,3-b]吡啶-2-甲酸乙酯 在 三氯氧磷 作用下， 以 吡啶 为溶剂， 生成 4-chloropyrido[3',2':4,5]thieno[3,2-d]pyrimidine
  参考文献：
  名称：

  吡啶并[3'，2'：4,5]噻吩并[3,2- d ]嘧啶衍生物的合成†

  摘要：

  吡啶并[3'，2'：4,5] thieno [3,2- d ]嘧啶及其衍生物已被合成。

  DOI：

  10.1002/jhet.5570110622

文献信息

• Tricyclic compounds capable of inhibiting tyrosine kinases of the
  申请人：Warner-Lambert Company

  公开号：US05679683A1

  公开（公告）日：1997-10-21

  Novel 4-substituted amino benzothieno\x9b3,2-d!pyrimidine and 4-substituted amino\x9b2,3-d!pyrimidine inhibitors of epidermal growth factor receptor family of tyrosine kinases are described, as well as pharmaceutical compositions of the same, which are useful in treating proliferative diseases such as cancer, synovial pannus invasion in arthritis, psoriasis, vascular restenosis and angiogenesis and additionally useful in the treatment of pancreatitis and kidney disease as well as a contraceptive agent.

  描述了一种新型的4-取代氨基苯并噻吩\9b3,2-d!嘧啶和4-取代氨基\9b2,3-d!嘧啶表皮生长因子受体家族的酪氨酸激酶抑制剂，以及相应的药物组合物，用于治疗增殖性疾病，如癌症、关节炎中的滑膜潘纳斯侵袭、牛皮癣、血管再狭窄和血管生成，此外还可用于胰腺炎和肾病的治疗，以及避孕剂。
• [EN] GLUCOSE UPTAKE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DU PRÉLÈVEMENT DU GLUCOSE ET LEURS UTILISATIONS
  申请人：METABOMED LTD

  公开号：WO2021095032A1

  公开（公告）日：2021-05-20

  The present invention relates to novel compounds that modulate cellular glucose uptake by affecting various targets, including, but not limited to those related to glycolysis and known transporters/co-transporters of the GLUT family. The compounds according to the invention are useful for treating cancer such as: neuroendrocrine neoplasms, gastrointestinal stromal tumors (GIST), renal cell carcinoma, paraganglioma, pheochromocytoma, pituitary adenoma, colorectal cancer, lung cancer, gastric cancer, pancreatic cancer sarcoma, head and neck cancer, melanoma, ovarian cancer and other cancers that rely on high levels of glycolysis for survival and proliferation; as well as in treating of autoimmune diseases, inflammation, infectious diseases, and metabolic diseases.

  本发明涉及一种新型化合物，通过影响各种靶标，包括但不限于与糖酵解和GLUT家族的已知转运体/共转运体相关的靶标，来调节细胞葡萄糖摄取。根据本发明的化合物可用于治疗癌症，如：神经内分泌肿瘤、胃肠道间质瘤（GIST）、肾细胞癌、副神经节瘤、嗜铬细胞瘤、垂体腺瘤、结直肠癌、肺癌、胃癌、胰腺癌、肉瘤、头颈癌、黑色素瘤、卵巢癌以及其他依赖高水平糖酵解进行生存和增殖的癌症；以及用于治疗自身免疫疾病、炎症、传染病和代谢性疾病。
• [EN] INHIBITORS OF MICROBIAL BETA-GLUCURONIDASE ENZYMES AND USES THEREOF<br/>[FR] INHIBITEURS DES ENZYMES BÊTA-GLUCURONIDASE MICROBIENNES ET LEURS UTILISATIONS
  申请人：UNIV NORTH CAROLINA CHAPEL HILL

  公开号：WO2018017874A1

  公开（公告）日：2018-01-25

  Compounds and compositions are provided that comprise selective b-glucuronidase inhibitors. The compounds and compositions can ameliorate the side effects of chemotherapeutic agents and can improve the efficacy of such agents, including irinotecan and non-steroidal anti-inflammatory drugs.

  提供了包含选择性β-葡萄糖苷酶抑制剂的化合物和组合物。这些化合物和组合物可以改善化疗药物的副作用，并提高这些药物的疗效，包括伊立替康和非甾体抗炎药。
• [EN] INHIBITORS OF MICROBIAL BETA-GLUCURONIDASE ENZYMES AND USES THEREOF<br/>[FR] INHIBITEURS D'ENZYMES BÊTA-GLUCURONIDASE MICROBIENNES ET LEURS UTILISATIONS
  申请人：UNIV NORTH CAROLINA CHAPEL HILL

  公开号：WO2018142365A1

  公开（公告）日：2018-08-09

  Methods utilizing compounds and compositions are provided that comprise selective β-glucuronidase inhibitors. The methods can ameliorate the side effects of chemotherapeutic agents and can improve the efficacy of such agents, including irinotecan and non-steroidal anti-inflammatory drugs. The methods comprise administering the compounds in combination with agents or administering the compounds in a monotherapy for the treatment of cancer and gastrointestinal conditions.

  提供了利用化合物和组合物的方法，其中包括选择性β-葡萄糖醛酸酶抑制剂。这些方法可以改善化疗药物的副作用，并提高这些药物的疗效，包括伊立替康和非甾体抗炎药。这些方法包括将这些化合物与药物一起使用或将这些化合物单独用于治疗癌症和胃肠道疾病。
• Discovery of Potent Antiproliferative Agents Targeting EGFR Tyrosine Kinase Based on the Pyrido[3′,2′:4,5]thieno[3,2-&lt;i&gt;d&lt;/i&gt;]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。