4-benzylaminothieno[2,3-d]pyrimidine | 63893-42-5

• 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-benzylaminothieno[2,3-d]pyrimidine
• 英文别名: benzyl-thieno[2,3-d]pyrimidin-4-yl-amine；N-benzylthieno[2,3-d]pyrimidin-4-amine
• CAS: 63893-42-5
• 化学式: C₁₃H₁₁N₃S
• mdl: MFCD03028502
• 分子量: 241.316
• InChiKey: KAWLVBDVIYJPHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氯噻吩[2,3-D]嘧啶 、 苄胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-benzylaminothieno[2,3-d]pyrimidine
  参考文献：
  名称：

  Wnt-pathway inhibitors with selective activity against triple-negative breast cancer: From thienopyrimidine to quinazoline inhibitors

  摘要：

  Wnt 通路在发育和组织稳态中起着关键作用，由于它在许多癌症中的异常激活，抗癌药物的开发日益受到关注。在这项研究中，我们发现了一种新型小分子系列，其噻吩嘧啶支架可作为依赖β-catenin的Wnt通路的下游抑制剂。我们利用依赖 Wnt 的三阴性乳腺癌（TNBC）细胞系对这种新型化学类型进行了研究。通过结构活性关系（SAR）探索，发现了 5a、5d、5e 等低微摩尔化合物以及 9d 等具有喹唑啉支架的新型系列化合物。进一步的研究表明，这些化合物具有抑制 HCC1395 和 MDA-MB-468 TNBC 细胞系癌症存活的活性，而不会影响非癌症乳腺上皮细胞系 MCF10a。这种抗增殖作用与多西他赛治疗具有协同作用。总之，我们发现了可作为依赖于β-catenin的Wnt通路下游抑制剂的新型化学类型，它们可以扩大治疗TNBC的选择范围。

  DOI：

  10.3389/fphar.2022.1045102

文献信息

• Mechanism of Drug Resistance of Hemagglutinin of Influenza Virus and Potent Scaffolds Inhibiting Its Function
  作者：Hiroshi Yanagita、Norio Yamamoto、Hideyoshi Fuji、Xinli Liu、Masakazu Ogata、Mizuho Yokota、Hiroshi Takaku、Hideki Hasegawa、Takato Odagiri、Masato Tashiro、Tyuji Hoshino

  DOI：10.1021/cb200332k

  日期：2012.3.16

  Highly pathogenic influenza viruses have become a global threat to humans. It is important to select an affective therapeutic option suitable for the subtypes in an epidemics or pandemic. To increase the options, the development of novel antiviral agents acting on targets different from those of the currently approved drugs is required. In this study. we performed molecular dynamics simulations on a spike protein on the viral envelop, hemagglutinin for the wild type and three kinds of mutants using a model system consisting of a trimeric hemagglutin complex, viral lipid membrane. solvation waters, and ions . A natural product stachyflin, which shows a high level of antiviral activity specific to some subtypes of influenza viruses, was examined on binding to the wild-type hemagglutinin was clarified. Next, 8 compounds were selected from a chemical database by in silico screening, considering the findings from the simulations. Inhibitory activities to suppress the proliferation of influenza virus were measured by cell-based antiviral assays, and chemical scaffolds were found to be potent for an inhibitor. More than 30 derivatives bearing either of these two chemical scaffolds were synthesized, and cell culture assays were carried out of evaluate the compound potency. Several derivatives displayed a high compound potency, and 50% effective concentrations of two synthesized compounds were below 1 mu M
• JP5765650
  申请人：——

  公开号：——

  公开（公告）日：——
• Wnt-pathway inhibitors with selective activity against triple-negative breast cancer: From thienopyrimidine to quinazoline inhibitors
  作者：Cédric Boudou、Luce Mattio、Alexey Koval、Valentin Soulard、Vladimir L. Katanaev

  DOI：10.3389/fphar.2022.1045102

  日期：——

  The Wnt-pathway has a critical role in development and tissue homeostasis and has attracted increased attention to develop anticancer drugs due to its aberrant activation in many cancers. In this study, we identified a novel small molecule series with a thienopyrimidine scaffold acting as a downstream inhibitor of the β-catenin-dependent Wnt-pathway. This novel chemotype was investigated using Wnt-dependent triple-negative breast cancer (TNBC) cell lines. Structure activity relationship (SAR) exploration led to identification of low micromolar compounds such as 5a, 5d, 5e and a novel series with quinazoline scaffold such as 9d. Further investigation showed translation of activity to inhibit cancer survival of HCC1395 and MDA-MB-468 TNBC cell lines without affecting a non-cancerous breast epithelial cell line MCF10a. This anti-proliferative effect was synergistic to docetaxel treatment. Collectively, we identified novel chemotypes acting as a downstream inhibitor of β-catenin-dependent Wnt-pathway that could expand therapeutic options to manage TNBC.

  Wnt 通路在发育和组织稳态中起着关键作用，由于它在许多癌症中的异常激活，抗癌药物的开发日益受到关注。在这项研究中，我们发现了一种新型小分子系列，其噻吩嘧啶支架可作为依赖β-catenin的Wnt通路的下游抑制剂。我们利用依赖 Wnt 的三阴性乳腺癌（TNBC）细胞系对这种新型化学类型进行了研究。通过结构活性关系（SAR）探索，发现了 5a、5d、5e 等低微摩尔化合物以及 9d 等具有喹唑啉支架的新型系列化合物。进一步的研究表明，这些化合物具有抑制 HCC1395 和 MDA-MB-468 TNBC 细胞系癌症存活的活性，而不会影响非癌症乳腺上皮细胞系 MCF10a。这种抗增殖作用与多西他赛治疗具有协同作用。总之，我们发现了可作为依赖于β-catenin的Wnt通路下游抑制剂的新型化学类型，它们可以扩大治疗TNBC的选择范围。