2-氯-N-(4-(4,4,5,5-四甲基-1,3,2-二噁硼戊环-2-基)苯基)乙酰胺 | 825630-79-3

• 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: 2-氯-N-(4-(4,4,5,5-四甲基-1,3,2-二噁硼戊环-2-基)苯基)乙酰胺
• 中文别名: 2-氯-N-(4-(4,4,5,5-四甲基-1,3,2-二硼戊环-2-基)苯基)乙酰胺
• 英文名称: 2-chloro-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide
• 英文别名: 2-chloro-N-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetamide；2-chloro-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamide
• CAS: 825630-79-3
• 化学式: C₁₄H₁₉BClNO₃
• 分子量: 295.574
• InChiKey: SDEMCVFPLGEVJY-UHFFFAOYSA-N

物化性质

• 沸点：
  450.8±30.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  20
• 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：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯-N-(4-(4,4,5,5-四甲基-1,3,2-二噁硼戊环-2-基)苯基)乙酰胺 在 lithium aluminium tetrahydride 、 二(氰基苯)二氯化钯 、 caesium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.34h， 生成 (E)-4-(5-hydroxy-2-phenyl-1-(4-((2-(piperidin-1-yl)ethyl)amino)phenyl)pent-1-en-1-yl)phenol dihydrochloride salt
  参考文献：
  名称：

  Insights of a Lead Optimization Study and Biological Evaluation of Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists

  摘要：

  We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERR gamma but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had comparable potency to 3 and were far more selective for ERR gamma over the ERR alpha, -beta, and ER alpha. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds. Additionally, we observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in 6g- or 10b treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, 6g and 10b-possess advantageous druglike properties and can be used to potentially treat various ERR gamma-related disorders.

  DOI：

  10.1021/acs.jmedchem.6b01204
• 作为产物：
  描述：

  氯乙酰氯 、 4-氨基苯硼酸频哪醇酯 以 二氯甲烷 为溶剂， 生成 2-氯-N-(4-(4,4,5,5-四甲基-1,3,2-二噁硼戊环-2-基)苯基)乙酰胺
  参考文献：
  名称：

  亚氨基吡啶酮和环炔烃在活细胞中快速和生物正交释放异氰酸酯

  摘要：

  生物正交点击和释放反应是化学生物学的强大工具，例如，允许在生物介质（包括动物体内）中选择性释放药物。在这里，我们开发了两个新的 iminosydnone 中离子反应物家族，它们允许在生理条件下生物正交释放亲电物质。已经详细研究了它们在与紧张炔烃的环加成反应中作为偶极子的合成和反应性。尽管通过实验证明了 pH 值对反应动力学的影响，但理论计算表明，与先前描述的亚氨基糖酮相比，新设计的偶极子显示出降低的共振稳定能量，这解释了它们具有更高的反应性。这些中离子化合物在生理条件下与环炔烃顺利反应，无铜反应条件与释放的烷基异氰酸酯或芳基异氰酸酯一起形成点击吡唑产物。速率常数高达 1000 M–1 s –1，这种点击和释放反应是迄今为止描述的最快的反应之一，代表了第一个允许在活细胞内释放异氰酸酯亲电子试剂的生物正交过程，为化学生物学提供了有趣的视角。

  DOI：

  10.1021/jacs.2c09865

文献信息

• Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors
  申请人：Sun Li Connie

  公开号：US20050009832A1

  公开（公告）日：2005-01-13

  The present invention relates to 8-amino-aryl-substituted imidazopyrazines which modulate the activity of protein kinases (“PKs”). The compounds of this invention are therefore useful in treating disorders related to abnormal PK activity. Pharmaceutical compositions comprising these compounds, methods of treating diseases utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.

  本发明涉及8-氨基-芳基取代的咪唑并吡嗪类化合物，这些化合物能够调节蛋白激酶（“PKs”）的活性。因此，本发明的化合物可用于治疗与异常PK活性相关的疾病。本发明还公开了包含这些化合物的药物组合物、使用包含这些化合物的药物组合物治疗疾病的方法以及它们的制备方法。
• Design and Optimization of Novel Benzimidazole- and Imidazo[4,5-<i>b</i>]pyridine-Based ATM Kinase Inhibitors with Subnanomolar Activities
  作者：Teodor Dimitrov、Athina Anastasia Moschopoulou、Lennart Seidel、Thales Kronenberger、Mark Kudolo、Antti Poso、Christian Geibel、Pascal Wölffing、Daniel Dauch、Lars Zender、Dieter Schollmeyer、Jürgen Bajorath、Michael Forster、Stefan Laufer

  DOI：10.1021/acs.jmedchem.2c02104

  日期：2023.6.8
• Insights of a Lead Optimization Study and Biological Evaluation of Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists
  作者：Jina Kim、Seo Yeon Woo、Chun Young Im、Eun Kyung Yoo、Seungmi Lee、Hyo-Ji Kim、Hee-Jong Hwang、Joong-heui Cho、Won Seok Lee、Heeseok Yoon、Shinae Kim、Oh-bin Kwon、Hayoung Hwang、Kyung-Hee Kim、Jae-Han Jeon、Thoudam Debraj Singh、Sang Wook Kim、Sung Yeoun Hwang、Hueng-Sik Choi、In-Kyu Lee、Seong Heon Kim、Yong Hyun Jeon、Jungwook Chin、Sung Jin Cho

  DOI：10.1021/acs.jmedchem.6b01204

  日期：2016.11.23

  We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERR gamma but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had comparable potency to 3 and were far more selective for ERR gamma over the ERR alpha, -beta, and ER alpha. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds. Additionally, we observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in 6g- or 10b treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, 6g and 10b-possess advantageous druglike properties and can be used to potentially treat various ERR gamma-related disorders.
• Fast and Bioorthogonal Release of Isocyanates in Living Cells from Iminosydnones and Cycloalkynes
  作者：Maxime Ribéraud、Karine Porte、Arnaud Chevalier、Léa Madegard、Aurélie Rachet、Agnès Delaunay-Moisan、Florian Vinchon、Pierre Thuéry、Giovanni Chiappetta、Pier Alexandre Champagne、Grégory Pieters、Davide Audisio、Frédéric Taran

  DOI：10.1021/jacs.2c09865

  日期：2023.2.1

  click-and-release reactions are powerful tools for chemical biology, allowing, for example, the selective release of drugs in biological media, including inside animals. Here, we developed two new families of iminosydnone mesoionic reactants that allow a bioorthogonal release of electrophilic species under physiological conditions. Their synthesis and reactivities as dipoles in cycloaddition reactions with strained

  生物正交点击和释放反应是化学生物学的强大工具，例如，允许在生物介质（包括动物体内）中选择性释放药物。在这里，我们开发了两个新的 iminosydnone 中离子反应物家族，它们允许在生理条件下生物正交释放亲电物质。已经详细研究了它们在与紧张炔烃的环加成反应中作为偶极子的合成和反应性。尽管通过实验证明了 pH 值对反应动力学的影响，但理论计算表明，与先前描述的亚氨基糖酮相比，新设计的偶极子显示出降低的共振稳定能量，这解释了它们具有更高的反应性。这些中离子化合物在生理条件下与环炔烃顺利反应，无铜反应条件与释放的烷基异氰酸酯或芳基异氰酸酯一起形成点击吡唑产物。速率常数高达 1000 M–1 s –1，这种点击和释放反应是迄今为止描述的最快的反应之一，代表了第一个允许在活细胞内释放异氰酸酯亲电子试剂的生物正交过程，为化学生物学提供了有趣的视角。