4-((1-methyl-1H-pyrrol-2-yl)methylene)isoquinoline-1,3(2H,4H)-dione | 1104546-89-5

• 物质功能分类: 生物化工 - 抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-((1-methyl-1H-pyrrol-2-yl)methylene)isoquinoline-1,3(2H,4H)-dione
• 英文别名: (4E)-4-[(1-methylpyrrol-2-yl)methylidene]isoquinoline-1,3-dione
• CAS: 1104546-89-5
• 化学式: C₁₅H₁₂N₂O₂
• 分子量: 252.272
• InChiKey: BTYSIDSTHDDAJW-UKTHLTGXSA-N

物化性质

• 沸点：
  492.5±45.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  51.1
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P272,P280,P302+P352,P333+P313,P363,P501
• 危险性描述：
  H317

制备方法与用途

生物活性

BYK204165 是一种有效的 poly(ADP-ribose) polymerase (PARP) 的选择性抑制剂。BYK204165 可抑制无细胞重组的人类PARP-1 (hPARP-1)对应的pIC50值和pKi值分别为7.35和7.05，对小鼠PARP-2 (mPARP-2)的pIC50值为5.38。

靶点

Target	Value
hPARP-1 (Cell-free assay)	7.35(pIC50)
hPARP-1 (Cell-free assay)	7.05(pKi)
mPARP-2 (Cell-free assay)	5.38(pIC50)

体外研究

In kinetic experiments with human PARP-1, BYK204165 exhibits potent and competitive inhibition of enzyme activity, yielding a pK _i value of 7.05.
BYK204165 exhibits low potency of PARP inhibition in C4I cells (pIC ₅₀ of 5.75).

体内研究

BYK204165 is not investigated in vivo because of its short half-time (t _1/2 ) of 23 min measured at rat microsomes in vitro.

反应信息

• 作为产物：
  描述：

  邻羧基苯乙酸 在 哌啶 、 ammonium hydroxide 作用下， 以 乙醇 、 邻二氯苯 、 苯 为溶剂， 反应 2.17h， 生成 化合物BYK204165 、 4-((1-methyl-1H-pyrrol-2-yl)methylene)isoquinoline-1,3(2H,4H)-dione
  参考文献：
  名称：

  4-亚苄基异喹啉-1,3( 2H , 4H )-二酮作为酪氨酰 DNA 磷酸二酯酶 2 (TDP2) 抑制剂

  摘要：

  酪氨酰-DNA 磷酸二酯酶 2 (TDP2) 修复拓扑异构酶 II (Top2) 介导的 DNA 损伤，包括支撑临床 Top2 毒物如依托泊苷 (ETP) 的抗癌机制的双链断裂 (DSB)。抑制 TDP2 可以通过增加 Top2 裂解复合物使癌细胞对 Top2 毒物敏感。我们之前已将异喹啉-1,3-二酮确定为 TDP2 的选择性抑制剂类型。然而，报告的结构-活性关系 (SAR) 仅限于异喹啉-1,3-二酮核心上的简单替换。在这里，我们报告了扩展的 SAR，包括对总共 50 种具有 N-2 和 C-4 修饰的类似物的合成和测试。主要的 SAR 观察结果包括 N-2 取代后效力的丧失、C-4 烯胺类似物（亚型11)，或任何其他 C-4 修饰（亚型13-15），但苯亚甲基取代（亚型12 ）除外，其中 8个类似物显示出低微摩尔效力。最好的类似物12q以 4.8 μM的 IC 50抑制 TDP2 。进行分子建模以帮助了解观察到的

  DOI：

  10.1007/s00044-020-02662-w

文献信息

• Induced extended pluripotent stem cells, method of making and using
  申请人：Beihao Stem Cell and Regenerative Medicine Research Institute Co., Ltd.

  公开号：US11028369B2

  公开（公告）日：2021-06-08

  Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.

  在体外培养后，延长分离的多能干细胞在体内产生胚外系的能力的因素，这里称为多能性化学延长剂（CEP）。延长多能细胞生成胚胎和胚外系能力的方法。将待重编程的细胞与有效量的 CEPS 接触足够长的时间，以将细胞重编程为化学诱导的扩展多能性细胞（ciEPSC）。ciEPSC 可根据以下特性确定为扩展多能性细胞：(i) 形态学上；(ii) 功能上，例如，根据它们在体内对 TE 和 ICM 的贡献能力。ciEPSCs 可培养或诱导分化为所需类型的细胞，并可用于多种应用，包括但不限于细胞疗法和组织工程。
• METHOD OF TREATING CANCER
  申请人：Academisch Medisch Centrum bij de Universiteit van Amsterdam

  公开号：EP2387403A1

  公开（公告）日：2011-11-23
• INDUCED EXTENDED PLURIPOTENT STEM CELLS, METHOD OF MAKING AND USING
  申请人：Beihao Stem Cell and Regenerative Medicine Research Institute Co., Ltd.

  公开号：US20180195046A1

  公开（公告）日：2018-07-12

  Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.
• [EN] METHOD OF TREATING CANCER<br/>[FR] PROCÉDÉ DE TRAITEMENT DU CANCER
  申请人：AMC AMSTERDAM

  公开号：WO2010082821A1

  公开（公告）日：2010-07-22

  The present invention relates to a method of treating or preventing hyperproliferative disease in a body tissue of a subject, comprising the steps of administering to a subject in need thereof a therapeutically effective amount of an agent that induces double strand breaks in the DNA of the hyperproliferative cells of said body tissue; and subjecting the hyperproliferative cells of said body tissue prior to, simultaneously with or subsequent to step a) to hyperthermia to thereby induce in said cells the degradation, inhibition and/or inactivation of BRCA2.