3-(4-吗啉基羰基)-5-硝基苯硼酸 | 871332-80-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 3-(4-吗啉基羰基)-5-硝基苯硼酸
• 中文别名: 3-(吗啉-4-羰基)-5-硝基苯基硼酸
• 英文名称: [3-(morpholine-4-carbonyl)-5-nitrophenyl]boronic acid
• 英文别名: (3-(Morpholine-4-carbonyl)-5-nitrophenyl)boronic acid
• CAS: 871332-80-8
• 化学式: C₁₁H₁₃BN₂O₆
• 分子量: 280.045
• InChiKey: GKGNPJBVECYLOT-UHFFFAOYSA-N

物化性质

• 熔点：
  167-169℃

计算性质

• 辛醇/水分配系数(LogP)：
  -1.25
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-(4-吗啉基羰基)-5-硝基苯硼酸 、 4-bromo-6-(but-3-en-1-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.25h， 生成 6-but-3-enyl-4-[3-(morpholine-4-carbonyl)-5-nitrophenyl]-1H-pyrrolo[2,3-c]pyridin-7-one
  参考文献：
  名称：

  GNE-371, a Potent and Selective Chemical Probe for the Second Bromodomains of Human Transcription-Initiation-Factor TFIID Subunit 1 and Transcription-Initiation-Factor TFIID Subunit 1-like

  摘要：

  The biological functions of the dual bromodomains of human transcription-initiation-factor TFIID subunit 1 (TAF1(1,2)) remain unknown, although TAF1 has been identified as a potential target for oncology research. Here, we describe the discovery of a potent and selective in vitro tool compound for TAF1(2), starting from a previously reported lead. A cocrystal structure of lead compound 2 bound to TAF1(2) enabled structure-based design and structure-activity-relationship studies that ultimately led to our in vitro tool compound, 27 (GNE-371). Compound 27 binds TAF1(2) with an IC(50 )of 10 nM while maintaining excellent selectivity over other bromodomain-family members. Compound 27 is also active in a cellular-TAF1(2) target-engagement assay (IC50 = 38 nM) and exhibits antiproliferative synergy with the BET inhibitor JQ1, suggesting engagement of endogenous TAF1 by 27 and further supporting the use of 27 in mechanistic and target-validation studies.

  DOI：

  10.1021/acs.jmedchem.8b01225

文献信息

• GNE-371, a Potent and Selective Chemical Probe for the Second Bromodomains of Human Transcription-Initiation-Factor TFIID Subunit 1 and Transcription-Initiation-Factor TFIID Subunit 1-like
  作者：Shumei Wang、Vickie Tsui、Terry D. Crawford、James E. Audia、Daniel J. Burdick、Maureen H. Beresini、Alexandre Côté、Richard Cummings、Martin Duplessis、E. Megan Flynn、Michael C. Hewitt、Hon-Ren Huang、Hariharan Jayaram、Ying Jiang、Shivangi Joshi、Jeremy Murray、Christopher G. Nasveschuk、Eneida Pardo、Florence Poy、F. Anthony Romero、Yong Tang、Alexander M. Taylor、Jian Wang、Zhaowu Xu、Laura E. Zawadzke、Xiaoyu Zhu、Brian K. Albrecht、Steven R. Magnuson、Steve Bellon、Andrea G. Cochran

  DOI：10.1021/acs.jmedchem.8b01225

  日期：2018.10.25

  The biological functions of the dual bromodomains of human transcription-initiation-factor TFIID subunit 1 (TAF1(1,2)) remain unknown, although TAF1 has been identified as a potential target for oncology research. Here, we describe the discovery of a potent and selective in vitro tool compound for TAF1(2), starting from a previously reported lead. A cocrystal structure of lead compound 2 bound to TAF1(2) enabled structure-based design and structure-activity-relationship studies that ultimately led to our in vitro tool compound, 27 (GNE-371). Compound 27 binds TAF1(2) with an IC(50 )of 10 nM while maintaining excellent selectivity over other bromodomain-family members. Compound 27 is also active in a cellular-TAF1(2) target-engagement assay (IC50 = 38 nM) and exhibits antiproliferative synergy with the BET inhibitor JQ1, suggesting engagement of endogenous TAF1 by 27 and further supporting the use of 27 in mechanistic and target-validation studies.