tert-butyl 2-{(9S,10S,18S,14R)-7,16,19-triaza-18-(carbamoylmethyl)-14-[(5-methylindolyl)methyl]-10-(4-nitrophenyl)-8,17,20-trioxospiro[5.14]icos-11-ene-9-yl}acetate | 852714-70-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 2-{(9S,10S,18S,14R)-7,16,19-triaza-18-(carbamoylmethyl)-14-[(5-methylindolyl)methyl]-10-(4-nitrophenyl)-8,17,20-trioxospiro[5.14]icos-11-ene-9-yl}acetate
• 英文别名: tert-butyl 2-[(9S,10S,11E,14R,18S)-18-(2-amino-2-oxoethyl)-14-[(5-methylindol-1-yl)methyl]-10-(4-nitrophenyl)-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-9-yl]acetate
• CAS: 852714-70-6
• 化学式: C₄₁H₅₂N₆O₈
• 分子量: 756.899
• InChiKey: IAKSMDFJCPVHQN-XEHQPBNZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  55
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  207
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-{(9S,10S,18S,14R)-7,16,19-triaza-18-(carbamoylmethyl)-14-[(5-methylindolyl)methyl]-10-(4-nitrophenyl)-8,17,20-trioxospiro[5.14]icos-11-ene-9-yl}acetate 在 ethandithiol 、 三氟乙酸 作用下， 反应 1.1h， 以16%的产率得到2-[(9S,10S,11E,14R,18S)-18-(2-amino-2-oxoethyl)-14-[(5-methylindol-1-yl)methyl]-10-(4-nitrophenyl)-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-9-yl]acetic acid
  参考文献：
  名称：

  Examination of Phosphoryl-Mimicking Functionalities within a Macrocyclic Grb2 SH2 Domain-Binding Platform

  摘要：

  Reported herein are the design, synthesis, and Grb2 SH2 domain-binding affinities of several phosphoryl-mimicking groups displayed within the context of a conformationally constrained macrocyclic platform. With use of surface plasmon resonance techniques, single-digit nanomolar affinities were exhibited by phosphonic acid and malonyl-containing diacidic phosphoryl mimetics (for 4h and 4g, K-D = 1.47 and 3.62 nM, respectively). Analogues containing monoacidic phosphoryl mimetics provided affinities of K-D = 16-67 nM. Neutral phosphoryl-mimicking groups did not show appreciable binding.

  DOI：

  10.1021/jm050059m
• 作为产物：
  描述：

  对硝基肉桂酸 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) N-甲基吗啉 、 lithium hydroxide 、 双氧水 、 苯硫酚铜(I) 、 三甲基乙酰氯 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 75.67h， 生成 tert-butyl 2-{(9S,10S,18S,14R)-7,16,19-triaza-18-(carbamoylmethyl)-14-[(5-methylindolyl)methyl]-10-(4-nitrophenyl)-8,17,20-trioxospiro[5.14]icos-11-ene-9-yl}acetate
  参考文献：
  名称：

  SH2 domain binding inhibitors

  摘要：

  揭示了由以下公式表示的化合物：或其药学上可接受的盐或异构体，其中R1-R6如规范中所定义。这些化合物被用作SH2结构域与磷酸蛋白结合的抑制剂，并可用于多种疾病，包括癌症。还揭示了包括本发明化合物和药学上可接受的载体的药物组合物。

  公开号：

  US20050119163A1

文献信息

• SH2 domain binding inhibitors
  申请人：Burke R. Terrence

  公开号：US20050119163A1

  公开（公告）日：2005-06-02

  Disclosed are compounds represented by the formula: or a pharmaceutically acceptable salt or isomer thereof, wherein R 1 -R 6 are as defined in the specification. These compounds are targeted for use as inhibitors of SH2 domain binding with a phosphoprotein, and are contemplated for use in a number of diseases including cancer. Also disclosed are pharmaceutical compositions comprising a compound of the invention and a pharmaceutically acceptable carrier.

  揭示了由以下公式表示的化合物：或其药学上可接受的盐或异构体，其中R1-R6如规范中所定义。这些化合物被用作SH2结构域与磷酸蛋白结合的抑制剂，并可用于多种疾病，包括癌症。还揭示了包括本发明化合物和药学上可接受的载体的药物组合物。
• Examination of Phosphoryl-Mimicking Functionalities within a Macrocyclic Grb2 SH2 Domain-Binding Platform
  作者：Sang-Uk Kang、Zhen-Dan Shi、Karen M. Worthy、Lakshman K. Bindu、Pathirage G. Dharmawardana、Sarah J. Choyke、Donald P. Bottaro、Robert J. Fisher、Terrence R. Burke

  DOI：10.1021/jm050059m

  日期：2005.6.1

  Reported herein are the design, synthesis, and Grb2 SH2 domain-binding affinities of several phosphoryl-mimicking groups displayed within the context of a conformationally constrained macrocyclic platform. With use of surface plasmon resonance techniques, single-digit nanomolar affinities were exhibited by phosphonic acid and malonyl-containing diacidic phosphoryl mimetics (for 4h and 4g, K-D = 1.47 and 3.62 nM, respectively). Analogues containing monoacidic phosphoryl mimetics provided affinities of K-D = 16-67 nM. Neutral phosphoryl-mimicking groups did not show appreciable binding.