2-chloro-3-(phenylethynyl)pyrido[3,2-b]pyrazine | 1338227-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶吡嗪类
• 英文名称: 2-chloro-3-(phenylethynyl)pyrido[3,2-b]pyrazine
• 英文别名: 2-Chloro-3-phenylethynylpyrido[2,3-b]pyrazine；2-chloro-3-(2-phenylethynyl)pyrido[2,3-b]pyrazine
• CAS: 1338227-54-5
• 化学式: C₁₅H₈ClN₃
• 分子量: 265.702
• InChiKey: GZLOSJLDFBUWJM-UHFFFAOYSA-N

物化性质

• 沸点：
  436.6±45.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-3-(phenylethynyl)pyrido[3,2-b]pyrazine 在 potassium [¹⁸F]fluoride 、 potassium carbonate 、 三乙胺 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.08h， 生成 2-(4-[18F]fluorobutoxy)-3-(phenylethynyl)pyrido[3,2-b]pyrazine
  参考文献：
  名称：

  F-18标记的吡咯并[3,2-B]吡嗪衍生物作为非小细胞肺癌的潜在显像剂的合成与评价

  摘要：

  吡咯并吡嗪衍生物被称为Wnt-2-β-catenin信号通路抑制剂。Wnt-2过度表达可能与非小细胞肺癌（NSCLC）有关。制备了一种新型的2-（4- [ 18 F]氟丁氧基）-3-（苯基乙炔基）吡啶并[3,2-b]吡嗪，以证明通过摄取Wnt-2蛋白可用于NSCLC成像剂。它是使用[ 18 F]氟化物与甲苯磺酸化的前体合成的，放射化学产率为44-48％。在细胞摄取评估中，H460和H1299，Wnt-2表达的癌细胞系显示，其细胞摄取比对照MCF10A高2.5倍。

  DOI：

  10.1002/bkcs.10335
• 作为产物：
  描述：

  1,4-二氢-吡啶并[2,3-b]吡嗪-2,3-二酮 在 copper(l) iodide 、 palladium diacetate 、 三乙胺 、 三苯基膦 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 27.0h， 生成 2-chloro-3-(phenylethynyl)pyrido[3,2-b]pyrazine
  参考文献：
  名称：

  F-18标记的吡咯并[3,2-B]吡嗪衍生物作为非小细胞肺癌的潜在显像剂的合成与评价

  摘要：

  吡咯并吡嗪衍生物被称为Wnt-2-β-catenin信号通路抑制剂。Wnt-2过度表达可能与非小细胞肺癌（NSCLC）有关。制备了一种新型的2-（4- [ 18 F]氟丁氧基）-3-（苯基乙炔基）吡啶并[3,2-b]吡嗪，以证明通过摄取Wnt-2蛋白可用于NSCLC成像剂。它是使用[ 18 F]氟化物与甲苯磺酸化的前体合成的，放射化学产率为44-48％。在细胞摄取评估中，H460和H1299，Wnt-2表达的癌细胞系显示，其细胞摄取比对照MCF10A高2.5倍。

  DOI：

  10.1002/bkcs.10335

文献信息

• Method for Inhibiting Transglutaminase 2 Activity Using 2-alkyloxy-3-phenylethynyl-4a,5-dihydropyrido[2,3-b]pyrazine Derivatives
  申请人：Gong Young Dae

  公开号：US20130164813A1

  公开（公告）日：2013-06-27

  The present invention relates to a method for inhibiting transglutaminase 2 activity using 2-alkyloxy-3-phenylethynyl-4a,5-dihydropyrido[2,3-b]pyrazine derivatives.

  本发明涉及使用2-烷氧基-3-苯乙炔基-4a,5-二氢吡啶[2,3-b]吡嗪衍生物抑制转谷氨酰胺酶2活性的方法。
• DGG-300273, a novel WNT/β-catenin inhibitor, induces apoptotic cell death by activating ROS-BIM signaling in a Wnt-dependent manner in colon cancer cells
  作者：Do Yeon Kim、Yea Seong Ryu、Eun-Sil Lee、Dong-In Koh、Jai-Hee Moon、Soo-A Jung、Mi Jin Kim、Hyeseon Yun、Ji-Eun You、Hong-Rae Jeong、Dong-Il Yoon、Chul Hee Kim、Seung-Woo Hong、Young-Dae Gong、Dong-Hoon Jin

  DOI：10.1007/s10637-022-01295-7

  日期：2023.2

  Dysregulated Wnt signaling is associated with malignant oncogenic transformation, especially in colon cancer. Recently, numerous drugs have been developed based on tumorigenesis biomarkers, thus having high potential as drug targets. Likewise, WNT/β-catenin pathway members are attractive therapeutic targets for colon cancer and are currently in various stages of development. However, although inhibitors of proteins regulating the WNT/β-catenin signaling pathway have been extensively studied, they have yet to be clinically approved, and the underlying molecular mechanism(s) of their anticancer effects remain poorly understood. Herein, we show that a novel WNT/β-catenin inhibitor, DGG-300273, inhibits colon cancer cell growth in a Wnt-dependent manner due to upregulation of the BCL2-family protein Bim and caspase-dependent apoptotic cell death. Additionally, DGG-300273-mediated cell death occurs by increased reactive oxygen species (ROS), as shown by abrogation of apoptotic cell death and ROS production following pretreatment with the antioxidant N-acetylcysteine. These results suggest that DGG-300273 represents a promising investigational drug for the treatment of Wnt-associated cancer, thus warranting further characterization and study.

  Wnt信号传导失调与恶性肿瘤转化有关，尤其是结肠癌。最近，基于肿瘤生物标志物开发了许多药物，因此具有很高的药物靶点潜力。同样，WNT/β-catenin通路成员也是结肠癌极具吸引力的治疗靶点，目前正处于不同的开发阶段。然而，尽管调节WNT/β-catenin信号传导通路的蛋白抑制剂已经过广泛研究，但尚未获得临床批准，其抗癌作用的潜在分子机制仍不为人所知。在此，我们展示了新型WNT/β-catenin抑制剂DGG-300273通过上调BCL2家族蛋白Bim和依赖半胱天冬酶的细胞凋亡，以Wnt依赖性方式抑制结肠癌细胞的生长。此外，DGG-300273介导的细胞死亡是通过增加活性氧（ROS）发生的，如用抗氧化剂N-乙酰半胱氨酸预处理后，细胞凋亡和ROS的产生被抑制。这些结果表明，DGG-300273是一种治疗Wnt相关癌症的有前景的研究药物，因此需要进一步表征和研究。
• A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/β-catenin pathway inhibitors in non-small-cell lung cancer cell lines
  作者：Young-Dae Gong、Mi-Sook Dong、Sang-Bum Lee、Nayeon Kim、Mi-Seon Bae、Nam-Sook Kang

  DOI：10.1016/j.bmc.2011.07.028

  日期：2011.9

  We developed Wnt/beta-catenin inhibitors by identifying 13 number of 3-arylethynyl-substituted pyrido[2,3,-b] pyrazine derivatives that were able to inhibit the Wnt/b-catenin signal pathway and cancer cell proliferation. In the optimization process, a series of 2,3,6-trisubstituted pyrido[2,3,-b] pyrazine core skeletons showed were shown to higher activity than 2,3,6-trisubstituted quinoxaline's and thus hold promise for use as potential small-molecule inhibitors of the Wnt/beta-catenin signal pathway in non-small-cell lung cancer cell (NSCLC) lines. And we have studied the pharmacophore mapping for compound 954, which presented the highest activity with a fit value of 2.81. The pharmacophore mapping for the compounds including 954, pyrido[2,3,-b] pyrazine core had hydrogen-bond acceptor site and hydrophobic center roles. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and Evaluation of F-18 Labeled Pyrido[3,2-B]pyrazine Derivative as a Potential Imaging Agent for Non-Small-Cell Lung Cancer
  作者：Jeong Hoon Park、Heejung Kim、Dong-Yeon Kim、Seung Dae Yang、Min Goo Hur、Sang Wook Kim、Kook Hyun Yu

  DOI：10.1002/bkcs.10335

  日期：2015.7

  Pyridopyrazine derivatives have been known as Wnt‐2/β‐catenin signaling pathway inhibitors. Wnt‐2 overexpression may be involved in non‐small‐cell lung cancer (NSCLC). A novel 2‐(4‐[ 18F]fluorobutoxy)‐3‐(phenylethynyl)pyrido[3,2‐b]pyrazine was prepared to demonstrate the feasibility of NSCLC imaging agent by uptake of Wnt‐2 protein. It was synthesized with tosylated precursor using [ 18F]fluoride in radiochemical

  吡咯并吡嗪衍生物被称为Wnt-2-β-catenin信号通路抑制剂。Wnt-2过度表达可能与非小细胞肺癌（NSCLC）有关。制备了一种新型的2-（4- [ 18 F]氟丁氧基）-3-（苯基乙炔基）吡啶并[3,2-b]吡嗪，以证明通过摄取Wnt-2蛋白可用于NSCLC成像剂。它是使用[ 18 F]氟化物与甲苯磺酸化的前体合成的，放射化学产率为44-48％。在细胞摄取评估中，H460和H1299，Wnt-2表达的癌细胞系显示，其细胞摄取比对照MCF10A高2.5倍。