N⁴-(furan-2-ylmethyl)-N²-(4-methoxyphenyl)quinazoline-2,4-diamine | 4510-35-4

• 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: N⁴-(furan-2-ylmethyl)-N²-(4-methoxyphenyl)quinazoline-2,4-diamine
• 英文别名: N4-(furan-2-ylmethyl)-N2-(4-methoxyphenyl)quinazoline-2,4-diamine；KHSP8；4-N-(furan-2-ylmethyl)-2-N-(4-methoxyphenyl)quinazoline-2,4-diamine
• CAS: 4510-35-4
• 化学式: C₂₀H₁₈N₄O₂
• 分子量: 346.389
• InChiKey: LVLNIGYBEQQXBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  72.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N⁴-(furan-2-ylmethyl)-N²-(4-methoxyphenyl)quinazoline-2,4-diamine 、 三氟乙酸 以 水 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  发现可激活SOS1介导的RAS上的核苷酸交换的喹唑啉。

  摘要：

  RAS家族中的蛋白质是细胞信号传导的重要调节剂，并且当突变时，可以驱动癌症的发病机理。尽管在过去30年中付出了巨大的努力，但RAS蛋白已被证明是顽固的治疗靶标。调节RAS信号的一种方法是靶向与RAS相互作用的蛋白，例如七无同源性1（SOS1）的鸟嘌呤核苷酸交换因子（GEF）。在这里，我们报告了对结合SOS1并激活RAS上的核苷酸交换的含喹唑啉类化合物的领先研究。使用基于结构的设计，我们优化了与喹唑啉核连接的取代基，并建立了在最初的HTS命中中不存在的其他相互作用。优化的化合物在体外以一位数的微摩尔浓度激活核苷酸交换。在HeLa细胞中，

  DOI：

  10.1021/acsmedchemlett.8b00296
• 作为产物：
  描述：

  2,4-喹唑啉二酮 在 盐酸 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 22.0h， 生成 N⁴-(furan-2-ylmethyl)-N²-(4-methoxyphenyl)quinazoline-2,4-diamine
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,4-diaminoquinazoline derivatives as novel heat shock protein 90 inhibitors

  摘要：

  Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.117

文献信息

• Optimization of 2-Anilino 4-Amino Substituted Quinazolines into Potent Antimalarial Agents with Oral in Vivo Activity
  作者：Paul R. Gilson、Cyrus Tan、Kate E. Jarman、Kym N. Lowes、Joan M. Curtis、William Nguyen、Adrian E. Di Rago、Hayley E. Bullen、Boris Prinz、Sandra Duffy、Jonathan B. Baell、Craig A. Hutton、Helene Jousset Subroux、Brendan S. Crabb、Vicky M. Avery、Alan F. Cowman、Brad E. Sleebs

  DOI：10.1021/acs.jmedchem.6b01673

  日期：2017.2.9

  Novel antimalarial therapeutics that target multiple stages of the parasite lifecycle are urgently required to tackle the emerging problem of resistance with current drugs. Here, we describe the optimization of the 2-anilino quinazoline class as antimalarial agents. The class, identified from publicly available antimalarial screening data, was optimized to generate lead compounds that possess potent

  迫切需要针对寄生虫生命周期多个阶段的新型抗疟疾疗法，以解决当前药物出现的耐药性问题。在这里，我们描述了2-苯胺基喹唑啉类作为抗疟剂的优化。从可公开获得的抗疟疾筛查数据确定的类别进行了优化，以生成对恶性疟原虫寄生虫具有有效抗疟疾活性的先导化合物，其与已知的抗疟疾，氯喹和甲氟喹相当。在优化过程中，我们定义了活性所必需的功能，并改善了体外代谢和溶解度。所得的铅化合物对恶性疟原虫的多药耐药菌株具有有效的活性。并在无性繁殖的环状期和寄生虫细胞期将寄生虫捕杀。最后，我们显示了在4天的疟疾疾病负担小鼠模型中，这些先导化合物具有口服有效作用。
• Synthesis and biological evaluation of 2,4-diaminoquinazoline derivatives as novel heat shock protein 90 inhibitors
  作者：Dhanaji Achyutrao Thorat、Munikumar Reddy Doddareddy、Seon Hee Seo、Tae-Joon Hong、Yong Seo Cho、Ji-Sook Hahn、Ae Nim Pae

  DOI：10.1016/j.bmcl.2011.01.117

  日期：2011.3

  Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS
  作者：Jason R. Abbott、Pratiq A. Patel、Jennifer E. Howes、Denis T. Akan、J. Phillip Kennedy、Michael C. Burns、Carrie F. Browning、Qi Sun、Olivia W. Rossanese、Jason Phan、Alex G. Waterson、Stephen W. Fesik

  DOI：10.1021/acsmedchemlett.8b00296

  日期：2018.9.13

  the RAS family are important regulators of cellular signaling and, when mutated, can drive cancer pathogenesis. Despite considerable effort over the last 30 years, RAS proteins have proven to be recalcitrant therapeutic targets. One approach for modulating RAS signaling is to target proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1)

  RAS家族中的蛋白质是细胞信号传导的重要调节剂，并且当突变时，可以驱动癌症的发病机理。尽管在过去30年中付出了巨大的努力，但RAS蛋白已被证明是顽固的治疗靶标。调节RAS信号的一种方法是靶向与RAS相互作用的蛋白，例如七无同源性1（SOS1）的鸟嘌呤核苷酸交换因子（GEF）。在这里，我们报告了对结合SOS1并激活RAS上的核苷酸交换的含喹唑啉类化合物的领先研究。使用基于结构的设计，我们优化了与喹唑啉核连接的取代基，并建立了在最初的HTS命中中不存在的其他相互作用。优化的化合物在体外以一位数的微摩尔浓度激活核苷酸交换。在HeLa细胞中，