9-fluoro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine

• 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: 9-fluoro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine
• 英文别名: 9-fluoro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazoline-5-amine；9-Fluoro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]quinazolin-5-ylamine
• 化学式: C₁₃H₈FN₅O
• 分子量: 269.238
• InChiKey: KQBHEYASZHOLFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氰基呋喃 在 硫酸 、 sodium methylate 、 氯化铵 作用下， 以 甲醇 、 乙醇 、 水 、 氯苯 、 异丙醇 为溶剂， 反应 6.0h， 生成 9-fluoro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine
  参考文献：
  名称：

  [EN] ARYL HYDROCARBON RECEPTOR (AHR) ACTIVATOR COMPOUNDS AS CANCER THERAPEUTICS
  [FR] COMPOSÉS ACTIVATEURS DU RÉCEPTEUR D'ARYL HYDROCARBONE (AHR) EN TANT QU'AGENTS THÉRAPEUTIQUES CONTRE LE CANCER

  摘要：

  本公开涉及与诊断和治疗或预防癌症有关的组合物和方法，特别是涉及表达FOXA1和/或FOXA1基因靶点升高的癌症，例如某些乳腺癌、肝癌和/或前列腺癌，包括乳腺癌的分泌性和/或ER阳性形式。已经确定的三种腺苷受体拮抗剂，CGS-15943、MRS-1220和SCH-58261，以及CGS-15943的呋喃环基团衍生物，专门用于以似乎涉及通过这些化合物激活芳香烃受体（AHR）来杀灭癌细胞。因此，本公开提供选择和/或施用CGS-15943、MRS-1220、SCH-58261和/或CGS-15943的呋喃基团衍生物，MRS-1220和/或SCH-58261作为靶向癌细胞和/或患有或有发展癌症风险的受试者的治疗剂的方法。还提供了包括这些化合物的治疗方法和组合物。

  公开号：

  WO2020102506A1

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。
• ARYL HYDROCARBON RECEPTOR (AHR) ACTIVATOR COMPOUNDS AS CANCER THERAPEUTICS
  申请人：THE BROAD INSTITUTE, INC.

  公开号：US20220017524A1

  公开（公告）日：2022-01-20

  The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of FOXA1 and/or FOXA1 gene targets, such as certain breast, liver and/or prostate cancers, including luminal and/or ER-positive forms of breast cancer. Three previously identified adenosine receptor antagonists, CGS-15943, MRS-1220 and SCH-58261, as well as furan ring moiety-possessing derivatives of CGS-15943 are specifically provided for killing cancer cells in a manner that appears to involve activation of the aryl hydrocarbon receptor (AHR) by such compounds. The instant disclosure therefore provides for selecting and/or administering CGS-15943, MRS-1220, SCH-58261 and/or a furan-possessing derivative of CGS-15943, MRS-1220 and/or SCH-58261 as a therapeutic agent to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided
• [EN] ARYL HYDROCARBON RECEPTOR (AHR) ACTIVATOR COMPOUNDS AS CANCER THERAPEUTICS<br/>[FR] COMPOSÉS ACTIVATEURS DU RÉCEPTEUR D'ARYL HYDROCARBONE (AHR) EN TANT QU'AGENTS THÉRAPEUTIQUES CONTRE LE CANCER
  申请人：BROAD INST INC

  公开号：WO2020102506A1

  公开（公告）日：2020-05-22

  The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of FOXA1 and/or FOXA1 gene targets, such as certain breast, liver and/or prostate cancers, including luminal and/or ER-positive forms of breast cancer. Three previously identified adenosine receptor antagonists, CGS-15943, MRS-1220 and SCH-58261, as well as furan ring moiety-possessing derivatives of CGS-15943 are specifically provided for killing cancer cells in a manner that appears to involve activation of the aryl hydrocarbon receptor (AHR) by such compounds. The instant disclosure therefore provides for selecting and/or administering CGS-15943, MRS-1220, SCH-58261 and/or a furan-possessing derivative of CGS-15943, MRS-1220 and/or SCH-58261 as a therapeutic agent to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided

  本公开涉及与诊断和治疗或预防癌症有关的组合物和方法，特别是涉及表达FOXA1和/或FOXA1基因靶点升高的癌症，例如某些乳腺癌、肝癌和/或前列腺癌，包括乳腺癌的分泌性和/或ER阳性形式。已经确定的三种腺苷受体拮抗剂，CGS-15943、MRS-1220和SCH-58261，以及CGS-15943的呋喃环基团衍生物，专门用于以似乎涉及通过这些化合物激活芳香烃受体（AHR）来杀灭癌细胞。因此，本公开提供选择和/或施用CGS-15943、MRS-1220、SCH-58261和/或CGS-15943的呋喃基团衍生物，MRS-1220和/或SCH-58261作为靶向癌细胞和/或患有或有发展癌症风险的受试者的治疗剂的方法。还提供了包括这些化合物的治疗方法和组合物。