guanidine, (4,6,8-trimethyl-2-quinazolinyl)

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: guanidine, (4,6,8-trimethyl-2-quinazolinyl)
• 英文别名: 1-(4,6,8-Trimethylquinazolin-2-yl)guanidine；2-(4,6,8-trimethylquinazolin-2-yl)guanidine
• 化学式: C₁₂H₁₅N₅
• mdl: MFCD01564341
• 分子量: 229.285
• InChiKey: KMCATZSTDZKZGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  guanidine, (4,6,8-trimethyl-2-quinazolinyl) 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N4-(3-(dimethylamino)propyl)-6-methyl-N2-(4,6,8-trimethylquinazolin-2-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  探索配体和 G4 DNA 之间芳烃-芳烃相互作用中的色散和静电成分以开发 G4-配体

  摘要：

  G-四链体 (G4) DNA 结构是中央生物过程中的重要调控元件。选择性结合并稳定G4结构的小分子具有治疗潜力，目前已知的G4配体有>1000。尽管如此，只有两种 G4 配体进入了临床试验。在这项工作中，我们合成了几种杂环G4配体，并使用生化测定研究了它们与G4（例如来自c-MYC 、 c-KIT和BCL-2启动子的G4）的相互作用。我们进一步研究了所选化合物对细胞活力的影响、对细胞中 G4 数量的影响及其药代动力学特性。这确定了具有合适特性的有效 G4 配体，并进一步揭示了芳烃-芳烃相互作用中的分散成分与缺电子静电相结合，对于配体与 G4 有效结合至关重要。所提出的设计策略可应用于进一步开发具有合适特性的 G4 配体，以探索 G4 作为治疗靶点。

  DOI：

  10.1021/acs.jmedchem.3c02127
• 作为产物：
  描述：

  2,4-二甲基苯胺 在 scandium tris(trifluoromethanesulfonate) 作用下， 以 水 、 乙腈 为溶剂， 生成 guanidine, (4,6,8-trimethyl-2-quinazolinyl)
  参考文献：
  名称：

  WO2023/39170

  摘要：

  公开号：

文献信息

• 2-Guanidinoquinazolines as new inhibitors of the STAT3 pathway
  作者：Matthew G. LaPorte、Dimas José da Paz Lima、Feng Zhang、Malabika Sen、Jennifer R. Grandis、Daniel Camarco、Yun Hua、Paul A. Johnston、John S. Lazo、Lynn O. Resnick、Peter Wipf、Donna M. Huryn

  DOI：10.1016/j.bmcl.2014.09.001

  日期：2014.11

  Synthesis and SAR investigation of 2-guanidinoquinazolines, initially identified in a high content screen for selective STAT3 pathway inhibitors, led to a more potent analog (11c) that demonstrated improved anti-proliferative activity against a panel of HNSCC cell lines.

  2-胍基喹唑啉的合成和 SAR 研究最初是在选择性 STAT3 通路抑制剂的高内涵筛选中发现的，产生了更有效的类似物 ( 11c )，该类似物表现出对一组 HNSCC 细胞系的抗增殖活性有所改善。
• Stimulation of natural killer cells with small molecule inhibitors of CD38 for the treatment of neuroblastoma
  作者：Catherine M. Mills、Thomas Z. Benton、Ivett Piña、Megan J. Francis、Leticia Reyes、Nathan G. Dolloff、Yuri K. Peterson、Patrick M. Woster

  DOI：10.1039/d2sc05749b

  日期：——

  Small molecule inhibitors of CD38 promote increases in interferon gamma and stimulate natural killer cell proliferation for the treatment of neuroblastoma.

  小分子抑制剂CD38促进干扰素γ的增加并刺激自然杀伤细胞增殖，用于神经母细胞瘤的治疗。
• Quinazolines as adenosine receptor antagonists: SAR and selectivity for A2B receptors
  作者：Thomas R Webb、Dmitriy Lvovskiy、Soon-Ai Kim、Xiao-duo Ji、Neli Melman、Joel Linden、Kenneth A Jacobson

  DOI：10.1016/s0968-0896(02)00323-1

  日期：2003.1

  We have recently reported the discovery of numerous new compounds that are selective inhibitors of all of the subtypes of the adenosine receptor family via a pharmacophore database searching and screening strategy. During the course of this work we made the unexpected discovery of a potent A(2B) receptor antagonist, 4-methyl-7-methoxyquinazolyl-2-(2'-amino-4'-imidazolinone) (38, CMB 6446), which showed selectivity for this receptor and functioned as an antagonist, with a binding K-i value of H 2 nM. We explored the effects of both substituent- and ring-structural variations on the receptor affinity in this series of derivatives, which were found to be mostly non-selective adenosine receptor ligands with K-i values in the micromolar range. Since no enhancement of A(2B) receptor affinity of 38 was achieved, the previously reported pharmacophore-based searching strategy yielded the most potent and selective structurally-related hit in the database originally searched. (C) 2002 Elsevier Science Ltd. All rights reserved.
• FP-Pocket-Binding Effectors and Methods for Using the Same to Modulate Telomerase Activity
  申请人：Skordalakes Emmanuel

  公开号：US20100158798A1

  公开（公告）日：2010-06-24

  The present invention embraces compounds selected for interacting with the Fingers-Palm pocket of telomerase and use thereof for modulating the activity of telomerase and preventing or treating diseases or conditions associated with telomerase.
• Screening Method and Compounds for Modulating Telomerase Activity
  申请人：Skordalakes Emmanuel

  公开号：US20120309759A1

  公开（公告）日：2012-12-06

  The present invention embraces methods for identifying compounds that modulate the activity of telomerase. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the TRBD, “thumb,” “finger,” and/or “palm” domain; or FP-pocket, PT-pocket or Th-pocket of telomerase and testing the compound for its ability to modulate the activity of telomerase. Compounds selected for interacting with the T-pocket or Fingers-Palm pocket of telomerase are also provided.