(3-(4-(2-hydroxyethyl)piperazine-1-carbonyl)phenyl)boronic acid | 957103-94-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3-(4-(2-hydroxyethyl)piperazine-1-carbonyl)phenyl)boronic acid
• 英文别名: 3-(4-(2-Hydroxyethyl)piperazine-1-carbonyl)phenylboronic acid；[3-[4-(2-hydroxyethyl)piperazine-1-carbonyl]phenyl]boronic acid
• CAS: 957103-94-5
• 化学式: C₁₃H₁₉BN₂O₄
• 分子量: 278.116
• InChiKey: JNYBKLWLMBEPIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.88
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Bromo-9-(2-chloro-3,6-difluorobenzyl)-6,7,8,9-tetrahydro-5H-pyrazino[2,3-b][1,4]diazepine 、 (3-(4-(2-hydroxyethyl)piperazine-1-carbonyl)phenyl)boronic acid 生成 {3-[9-(2-chloro-3,6-difluorobenzyl)-6,7,8,9-tetrahydro-5H-pyrazino[2,3-b][1,4]diazepin-2-yl]phenyl}[4-(2-hydroxyethyl)piperazin-1-yl]-methanone
  参考文献：
  名称：

  PYRAZINOPYRAZINES AND DERIVATIVES AS KINASE INHIBITORS

  摘要：

  本发明涉及以下通式的化合物：其中变量基团如本文所定义，以及它们的制备和使用。

  公开号：

  US20110288078A1

文献信息

• Pyrazinopyrazines and derivatives as kinase inhibitors
  申请人：Huang Wei-Sheng

  公开号：US08846664B2

  公开（公告）日：2014-09-30

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及一般式化合物：其中变量基团如本文所定义，以及它们的制备和使用。
• 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.