5-(4-硝基苯基)-噻吩并[2,3-d]嘧啶-4-胺 | 501696-27-1

• 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
• 中文名称: 5-(4-硝基苯基)-噻吩并[2,3-d]嘧啶-4-胺
• 英文名称: 5-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4-amine
• 英文别名: 4-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4-amine；4-amino-5-(4-nitrophenyl)-thieno[2,3-d]pyrimidine
• CAS: 501696-27-1
• 化学式: C₁₂H₈N₄O₂S
• 分子量: 272.287
• InChiKey: VZCWJPQAZHGISU-UHFFFAOYSA-N

物化性质

• 熔点：
  >225 °C(Solv: acetone (67-64-1))
• 沸点：
  541.5±50.0 °C(Predicted)
• 密度：
  1.522±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(4-硝基苯基)-噻吩并[2,3-d]嘧啶-4-胺 在 铁粉 、 氯化铵 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-[4-(4-aminothieno[2,3-d]pyrimidin-5-yl)-phenyl]-N'-(3-methylphenyl)urea
  参考文献：
  名称：

  Thienopyrimidine Ureas as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors

  摘要：

  A series of novel thienopyrimidine-based receptor tyrosine kinase inhibitors has been discovered. Investigation of structure-activity relationships at the 5- and 6-positions of the thienopyrimidine nucleus led to a series of N,N '-diaryl ureas that potently inhibit all of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. A kinase insert domain-containing receptor (KDR) homology model suggests that these compounds bind to the "inactive conformation" of the enzyme with the urea portion extending into the back hydrophobic pocket adjacent to the adenosine 5 '-triphosphate (ATP) binding site. A number of compounds have been identified as displaying excellent in vivo potency. In particular, compounds 28 and 76 possess favorable pharmacokinetic (PK) profiles and demonstrate potent antitumor efficacy against the HT1080 human fibrosarcoma xenograft tumor growth model (tumor growth inhibition (TGI) = 75% at 25 mg/kg-day, per os (po)).

  DOI：

  10.1021/jm050458h
• 作为产物：
  描述：

  2-氨基-4-(4-硝基苯基)-3-噻吩甲腈 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 19.0h， 生成 5-(4-硝基苯基)-噻吩并[2,3-d]嘧啶-4-胺
  参考文献：
  名称：

  Thiopyrimidine and isothiazolopyrimidine kinase inhibitors

  摘要：

  具有以下化学式的化合物对抑制蛋白酪氨酸激酶具有用处。本发明还公开了制备这些化合物的方法、含有这些化合物的组合物，以及使用这些化合物进行治疗的方法。

  公开号：

  US20030225273A1

文献信息

• A One-Step, Atom Economical Synthesis of Thieno[2,3-<i>d</i> ]pyrimidin-4-amine Derivatives by a Four-Component Reaction
  作者：Taoda Shi、ChristopherJ. Zerio、Jared Sivinski、Andrew J. Ambrose、Kohlson T. Moore、Thomas Buckley、Lynn Kaneko、Mae Zhang、Donna D. Zhang、Eli Chapman

  DOI：10.1002/ejoc.201900414

  日期：2019.6.2

  A Na2HPO4-catalyzed four-component reaction between a ketone, malononitrile, S8 and formamide has been realized for the first time. This reaction provides a concise approach to thieno[2,3-d]pyrimidin-4-amines, previously requiring 5 steps. The utility of this reaction was validated by preparing a multi-targeted kinase inhibitor and an inhibitor of the NRF2 pathway with excellent atom- and step-economy

  首次实现了Na2HPO4催化酮、丙二腈、S8和甲酰胺之间的四组分反应。该反应提供了一种制备噻吩并[2,3-d]嘧啶-4-胺的简洁方法，之前需要 5 个步骤。通过制备具有优异原子经济性和步骤经济性的多靶点激酶抑制剂和 NRF2 途径抑制剂，验证了该反应的实用性。
• Discovery of thienopyrimidine-based inhibitors of the human farnesyl pyrophosphate synthase—Parallel synthesis of analogs via a trimethylsilyl ylidene intermediate
  作者：Chun-Yuen Leung、Adrienne M. Langille、John Mancuso、Youla S. Tsantrizos

  DOI：10.1016/j.bmc.2013.02.006

  日期：2013.4

  (hFPPS). Analogs were prepared via cyclization of 2-(1-(trimethylsilyl)ethylidene)malononitrile to 2-amino-4-(trimethylsilyl)thiophene-3-carbonitrile in the presence of elemental sulfur. Direct ipso-iododesilylation of this intermediate led to selective iodination at Cβ of the sulfur atom in high efficiency. The synthetic protocols developed were used in the parallel synthesis of structurally diverse thieno[2

  基于硫代嘧啶的双膦酸酯被鉴定为人法呢基焦磷酸合酶（hFPPS）的一类新型的含氮双膦酸酯（N-BP）抑制剂。在元素硫的存在下，通过将2-（1-（三甲基甲硅烷基）亚乙基）丙二腈环化成2-氨基-4-（三甲基甲硅烷基）噻吩-3-甲腈来制备类似物。引导本位该中间导致了选择性碘化中C的-iododesilylation β在高效率的硫原子的。所开发的合成方案被用于结构平行的hFPPS的基于硫杂[2,3 - d ]嘧啶-4-胺的双膦酸酯抑制剂的合成。
• Crystalline N-(4-(4-aminothieno[2,3-d]pyrimidin-5-yl)phenyl)-N'-(2-fluoro-5-(trifluoromethyl)phenyl)urea ethanolate
  申请人：Mellican M. Sean

  公开号：US20070155758A1

  公开（公告）日：2007-07-05

  A crystalline N-(4-(4-aminothieno[2,3-d]pyrimidin-5-yl)phenyl)-N′-[2-fluoro-5-(trifluoromethyl)phenyl)urea ethanolate, ways to make it, compositions comprising it, and methods of treatment using it are disclosed.

  揭示了一种结晶的N-(4-(4-氨基噻吩[2,3-d]嘧啶-5-基)苯基)-N′-[2-氟-5-(三氟甲基)苯基)脲乙醇盐，制备方法，含有该物质的组合物，以及使用它的治疗方法。
• Crystalline N-(4-(4-ammoniumthieno[2,3-d]pyrimidin-5-yl)phenyl)-N'-(2-fluoro-5-(trifluoromethyl)phenyl)urea ethanesulfonate
  申请人：Mellican M. Sean

  公开号：US20070161661A1

  公开（公告）日：2007-07-12

  A crystalline N-(4-(4-ammoniumthieno[2,3-d]pyrimidin-5-yl)phenyl)-N′-(2-fluoro-5-(trifluoromethyl)phenyl)urea ethanesulfonate, ways to make it, compositions comprising it, and methods of treatment using it are disclosed.

  本文披露了一种晶体N-(4-(4-铵基噻吩[2,3-d]嘧啶-5-基)苯基)-N′-(2-氟-5-(三氟甲基)苯基)脲乙烷磺酸盐，以及制备该化合物的方法、含有该化合物的组合物，以及使用该化合物进行治疗的方法。
• Crystalline N-(4-(4-aminothieno[2,3-d]pyrimidin-5-yl)phenyl)-N'-(2-fluoro-5-(trifluoromethyl)phenyl)urea hydrochloride
  申请人：Mellican Sean M.

  公开号：US20090270424A1

  公开（公告）日：2009-10-29

  A crystalline N-(4-(4-aminothieno[2,3-d]pyrimidin-5-yl)phenyl)-N′-[2-fluoro-5-(trifluoromethyl)phenyl)urea hydrochloride, ways to make it, compositions comprising it, and methods of treatment using it are disclosed.

  本文公开了一种晶体N-(4-(4-氨基噻吩[2,3-d]嘧啶-5-基)苯基)-N'-[2-氟-5-(三氟甲基)苯基]脲盐酸盐，其制备方法、包含它的组合物以及使用它的治疗方法。