2-(2-furyl)-5-(benzylamino)-9-chloro[1,2,4]triazolo[1,5-c]quinazoline

• 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: 2-(2-furyl)-5-(benzylamino)-9-chloro[1,2,4]triazolo[1,5-c]quinazoline
• 英文别名: Benzyl-(9-chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-amine；N-benzyl-9-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine
• 化学式: C₂₀H₁₄ClN₅O
• 分子量: 375.817
• InChiKey: LREUJMKERSIZBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-5-氯苯甲酰肼 在 Pd(opiv)2 、 氧气 、 sodium methylate 作用下， 以 2-甲基四氢呋喃 、 乙醇 为溶剂， 75.0 ℃ 、101.33 kPa 条件下， 反应 121.0h， 生成 2-(2-furyl)-5-(benzylamino)-9-chloro[1,2,4]triazolo[1,5-c]quinazoline
  参考文献：
  名称：

  钯（II）催化异氰酸酯的好氧氧化插入合成偶氮[c]喹唑啉

  摘要：

  我们报告了使用空气作为化学计量氧化剂，钯（II）催化的异氰酸酯与各种（2-氨基苯基）唑类的好氧氧化偶联。通过这种新方法，获得了多种医学上有价值的氮杂[ c ]喹唑啉。

  DOI：

  10.1002/adsc.201301129

文献信息

• Phenotypic Discovery of Triazolo[1,5-<i>c</i>]quinazolines as a First-In-Class Bone Morphogenetic Protein Amplifier Chemotype
  作者：Fabian Wesseler、Stefan Lohmann、Daniel Riege、Jonas Halver、Aileen Roth、Christian Pichlo、Sabrina Weber、Masanari Takamiya、Eva Müller、Jana Ketzel、Jana Flegel、Adrian Gihring、Sepand Rastegar、Jessica Bertrand、Ulrich Baumann、Uwe Knippschild、Christian Peifer、Sonja Sievers、Herbert Waldmann、Dennis Schade

  DOI：10.1021/acs.jmedchem.2c01199

  日期：2022.11.24

  Phenotypic drug discovery (PDD) continues to fuel the research and development pipelines with first-in-class therapeutic modalities, but success rates critically depend on the quality of the underlying model system. Here, we employed a stem cell-based approach for the target-agnostic, yet pathway-centric discovery of small-molecule cytokine signaling activators to act as morphogens during development and

  表型药物发现 (PDD) 继续以一流的治疗方式推动研发管道，但成功率主要取决于基础模型系统的质量。在这里，我们采用了一种基于干细胞的方法来发现与目标无关但以通路为中心的小分子细胞因子信号激活剂，以在发育和再生过程中充当形态发生素。公正筛选鉴定出三唑并 [1,5- c]喹唑啉作为骨形态发生蛋白 (BMP) 通路的体外和体内活性放大器。细胞 BMP 输出通过 BMP-Smad 蛋白的增强和持续可用性来刺激，严格依赖于最小的 BMP 输入。整体目标反卷积揭示了一种独特的双重靶向机制，即酪蛋白激酶 1 和磷脂酰肌醇 3-激酶同种型作为有效放大成骨 BMP 信号传导的关键效应物。这项工作强调了 PDD 发现未被识别的多药理学特征的资产，在这种情况下显着扩展了 BMP 调制器的化学和药物空间。
• Derivatives of the Triazoloquinazoline Adenosine Antagonist (CGS 15943) Having High Potency at the Human A_2B and A₃ Receptor Subtypes
  作者：Yong-Chul Kim、Maarten de Zwart、Louis Chang、Stefano Moro、Jacobien K. von Frijtag Drabbe Künzel、Neli Melman、Ad P. IJzerman、Kenneth A. Jacobson

  DOI：10.1021/jm980094b

  日期：1998.7.1

  The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS 15943) binds nonselectively to human A(1), A(2A), and A(3) receptors with high affinity. Acylated derivatives and one alkyl derivative of the 5-amino group and other modifications were prepared in an effort to enhance A(2B) or A(3) subtype potency. In general, distal modifications of the N-5-substituent were highly modulatory to potency and selectivity at adenosine receptors, as determined in radioligand binding assays at rat brain A(1) and A(2A) receptors and at recombinant human A(3) receptors. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, inhibition of agonist-induced cyclic AMP production was measured. An N-5-(2-iodophenyl)acetyl derivative was highly selective for A(2A) receptors. An (R)-N-5-alpha-methyl-(phenylacetyl) derivative was the most potent derivative at A(3) receptors, with a K-i value of 0.36 nM. A bulky N-5-diphenylacetyl derivative, 13, displayed a K-i value of 0.59 nM at human A(3) receptors and was moderately selective for that subtype. Thus, a large, nondiscriminating hydrophobic region occurs in the Ag receptor in proximity to the N-5-substituent. A series of straight-chain N-5-aminoalkylacyl derivatives demonstrated that for A(2B) receptors the optimal chain length occurs with three methylene groups, i.e., the N-5-gamma-aminobutyryl derivative 27 which had a pA(2) value of 8.0 but was not selective for A(2B) receptors. At A(1), A(2A), and A(3) receptors however the optimum occurs with four methylene groups. An N-5-pivaloyl derivative, which was less potent than 27 at A(1), A(2A), and A(3) receptors, retained moderate potency at A(2B) receptors. A molecular model of the 27-A(2B) receptor complex based on the structure of rhodopsin utilizing a "cross-docking" procedure was developed in order to visualize the environment of the ligand binding site.
• Synthesis of Diverse Azolo[<i>c</i>]quinazolines by Palladium(II)- Catalyzed Aerobic Oxidative Insertion of Isocyanides
  作者：Tjøstil Vlaar、Lisa Bensch、Jasper Kraakman、Christophe M. L. Vande Velde、Bert U. W. Maes、Romano V. A. Orru、Eelco Ruijter

  DOI：10.1002/adsc.201301129

  日期：2014.4.14

  We report the palladium(II)‐catalyzed aerobic oxidative coupling of isocyanides with various (2‐aminophenyl)azoles using air as the stoichiometric oxidant. A diverse range of medicinally valuable azolo[c]quinazolines was obtained by this new approach.

  我们报告了使用空气作为化学计量氧化剂，钯（II）催化的异氰酸酯与各种（2-氨基苯基）唑类的好氧氧化偶联。通过这种新方法，获得了多种医学上有价值的氮杂[ c ]喹唑啉。