3-(环己基(甲基)氨基甲酰)苯硼酸 | 1072945-73-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(环己基(甲基)氨基甲酰)苯硼酸
• 英文名称: (3-(cyclohexyl(methyl)carbamoyl)phenyl)boronic acid
• 英文别名: [3-[cyclohexyl(methyl)carbamoyl]phenyl]boronic acid
• CAS: 1072945-73-3
• 化学式: C₁₄H₂₀BNO₃
• 分子量: 261.129
• InChiKey: MFWBKTUXYRRWCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.77
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2931900090

反应信息

• 作为反应物：
  描述：

  3-(环己基(甲基)氨基甲酰)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 0.17h， 生成 3-(6-(but-3-en-1-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-N-cyclohexyl-N-methylbenzamide
  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.