1-(4-(4-(4-amino-3-(4-fluoro-3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)piperazin-1-yl)ethanone | 1603845-25-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-(4-(4-amino-3-(4-fluoro-3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)piperazin-1-yl)ethanone
• 英文别名: 1-(4-(4-(4-Amino-3-(4-fluoro-3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)piperazin-1-yl)ethan-1-one；1-[4-[4-[4-amino-3-(4-fluoro-3-nitrophenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]piperazin-1-yl]ethanone
• CAS: 1603845-25-5
• 化学式: C₂₃H₂₇FN₈O₃
• 分子量: 482.518
• InChiKey: SUQBAQXKMHFVRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(4-(4-(4-amino-3-(4-fluoro-3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)piperazin-1-yl)ethanone 在 4-二甲氨基吡啶 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 tert-butyl (1-(4-(4-acetylpiperazin-1-yl)cyclohexyl)-3-(3-amino-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-[((tert-butoxy)carbonyl)]carbamate
  参考文献：
  名称：

  [EN] HYDROPHOBICALLY TAGGED SMALL MOLECULES AS INDUCERS OF PROTEIN DEGRADATION
  [FR] PETITES MOLÉCULES MARQUÉES DE FAÇON HYDROPHOBE EN TANT QU'INDUCTEURS DE LA DÉGRADATION DE PROTÉINE

  摘要：

  提供了化学式(I)的双功能小分子，或其药用盐，其中M代表一个小有机分子，可以共价或非共价结合激酶，如Her3蛋白激酶；L1代表一个连接物；RH代表一个疏水基团。化合物化学式(I)的一个例子是化合物化学式(II)。还提供了包含化学式(I)或(II)的药物组合物，以及使用这些化合物治疗增殖性疾病的方法。

  公开号：

  WO2014063061A1
• 作为产物：
  描述：

  4-羟基环己酮乙二醇缩醛 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 1,2-二氯乙烷 为溶剂， 生成 1-(4-(4-(4-amino-3-(4-fluoro-3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  Development of small molecules targeting the pseudokinase Her3

  摘要：

  Her3 is a member of the human epidermal growth factor receptor (EGFR) tyrosine kinase family, and it is often either overexpressed or deregulated in many types of human cancer. Her3 has not been the subject of small-molecule inhibitor development because it is a pseudokinase and does not possess appreciable kinase activity. We recently reported on the development of the first selective irreversible Her3 ligand (TX1-85-1) that forms a covalent bond with cysteine 721 which is unique to Her3 among all kinases. We also developed a bi-functional compound (TX2-121-1) containing a hydrophobic adamantane moiety and the same warhead of TX1-85-1 that is capable of inhibiting Her3-dependent signaling and growth. Here we report on the structure-based medicinal chemistry effort that resulted in the discovery of these two compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.103

文献信息

• HYDROPHOBICALLY TAGGED SMALL MOLECULES AS INDUCERS OF PROTEIN DEGRADATION
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20150274738A1

  公开（公告）日：2015-10-01

  Provided are bifunctional small molecules of Formula (I): or pharmaceutically acceptable salts thereof, wherein M represents a small organic molecule which binds, covalently or non-covalently, a kinase, such as Her3 protein kinase; L 1 represents a linker; and R H represents a hydrophobic group. An example of a compound of Formula (I) is a compound of Formula (II): Also provided are pharmaceutical compositions comprising a compound of Formula (I) or (II) and methods of using such compounds for treating proliferative diseases.

  提供的是公式（I）的双功能小分子或其药学上可接受的盐，其中M代表结合激酶的小有机分子，可以是共价或非共价结合，例如Her3蛋白激酶；L1代表连接物；RH代表疏水基团。公式（I）的一个化合物示例是公式（II）的化合物： 还提供了包含公式（I）或（II）化合物的药物组合物，以及使用这些化合物治疗增殖性疾病的方法。
• US9758522B2
  申请人：——

  公开号：US9758522B2

  公开（公告）日：2017-09-12
• USRE48175E1
  申请人：——

  公开号：USRE48175E1

  公开（公告）日：2020-08-25
• Development of small molecules targeting the pseudokinase Her3
  作者：Sang Min Lim、Ting Xie、Kenneth D. Westover、Scott B. Ficarro、Hyun Seop Tae、Deepak Gurbani、Taebo Sim、Jarrod A. Marto、Pasi A. Jänne、Craig M. Crews、Nathanael S. Gray

  DOI：10.1016/j.bmcl.2015.04.103

  日期：2015.8

  Her3 is a member of the human epidermal growth factor receptor (EGFR) tyrosine kinase family, and it is often either overexpressed or deregulated in many types of human cancer. Her3 has not been the subject of small-molecule inhibitor development because it is a pseudokinase and does not possess appreciable kinase activity. We recently reported on the development of the first selective irreversible Her3 ligand (TX1-85-1) that forms a covalent bond with cysteine 721 which is unique to Her3 among all kinases. We also developed a bi-functional compound (TX2-121-1) containing a hydrophobic adamantane moiety and the same warhead of TX1-85-1 that is capable of inhibiting Her3-dependent signaling and growth. Here we report on the structure-based medicinal chemistry effort that resulted in the discovery of these two compounds. (C) 2015 Elsevier Ltd. All rights reserved.
• [EN] HYDROPHOBICALLY TAGGED SMALL MOLECULES AS INDUCERS OF PROTEIN DEGRADATION<br/>[FR] PETITES MOLÉCULES MARQUÉES DE FAÇON HYDROPHOBE EN TANT QU'INDUCTEURS DE LA DÉGRADATION DE PROTÉINE
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2014063061A1

  公开（公告）日：2014-04-24

  Provided are bifunctional small molecules of Formula (I): or pharmaceutically acceptable salts thereof, wherein M represents a small organic molecule which binds, covalently or non-covalently, a kinase, such as Her3 protein kinase; L1 represents a linker; and RH represents a hydrophobic group. An example of a compound of Formula (I) is a compound of Formula (II): Also provided are pharmaceutical compositions comprising a compound of Formula (I) or (II) and methods of using such compounds for treating proliferative diseases.

  提供了化学式(I)的双功能小分子，或其药用盐，其中M代表一个小有机分子，可以共价或非共价结合激酶，如Her3蛋白激酶；L1代表一个连接物；RH代表一个疏水基团。化合物化学式(I)的一个例子是化合物化学式(II)。还提供了包含化学式(I)或(II)的药物组合物，以及使用这些化合物治疗增殖性疾病的方法。