4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)benzaldehyde | 1312201-10-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)benzaldehyde
• 英文别名: 4-[[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methoxy]benzaldehyde
• CAS: 1312201-10-7
• 化学式: C₂₀H₂₃BO₄
• 分子量: 338.211
• InChiKey: CXBJOGJONATCLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)benzaldehyde 在 sodium periodate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 5.5h， 生成 (E)-(4-((4-((2,5-dioxopyrrolidin-3-ylidene)methyl)phenoxy)methyl)phenyl)boronic acid
  参考文献：
  名称：

  Structure-Based Design of Novel Boronic Acid-Based Inhibitors of Autotaxin

  摘要：

  Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in inflammation, fibrosis, and tumor progression, rendering ATX an attractive drug target. We recently described a boronic add-based inhibitor of ATX, named HA155 (1). Here, we report the design of new inhibitors based on the crystal structure of ATX in complex with inhibitor 1. Furthermore, we describe the syntheses and activities of these new inhibitors, whose potencies can be explained by structural data. To understand the difference in activity between two different isomers with nanomolar potencies, we performed molecular docking experiments. Intriguingly, molecular docking suggested a remarkable binding pose for one of the isomers, which differs from the original binding pose of inhibitor 1 for ATX, opening further options for inhibitor design.

  DOI：

  10.1021/jm200310q
• 作为产物：
  描述：

  对溴溴苄 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 19.0h， 生成 4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)benzaldehyde
  参考文献：
  名称：

  Structure-Based Design of Novel Boronic Acid-Based Inhibitors of Autotaxin

  摘要：

  Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in inflammation, fibrosis, and tumor progression, rendering ATX an attractive drug target. We recently described a boronic add-based inhibitor of ATX, named HA155 (1). Here, we report the design of new inhibitors based on the crystal structure of ATX in complex with inhibitor 1. Furthermore, we describe the syntheses and activities of these new inhibitors, whose potencies can be explained by structural data. To understand the difference in activity between two different isomers with nanomolar potencies, we performed molecular docking experiments. Intriguingly, molecular docking suggested a remarkable binding pose for one of the isomers, which differs from the original binding pose of inhibitor 1 for ATX, opening further options for inhibitor design.

  DOI：

  10.1021/jm200310q

文献信息

• Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity
  作者：Ruifang Jia、Jian Zhang、Chiara Bertagnin、Srinivasulu Cherukupalli、Wei Ai、Xiao Ding、Zhuo Li、Jiwei Zhang、Han Ju、Xiuli Ma、Arianna Loregian、Bing Huang、Peng Zhan、Xinyong Liu

  DOI：10.1016/j.ejmech.2020.113097

  日期：2021.2

  Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C5–NH2 of oseltamivir targeting 150-cavity. Among them, compound

  在我们较早发现N1选择性抑制剂的鼓舞下，可以进一步利用150腔流感病毒神经氨酸酶（NAs）来产生更有效的奥司他韦衍生物。在这里，我们通过靶向150腔的奥司他韦的C 5 -NH 2结构修饰，报道了一系列新型奥司他韦衍生物的设计，合成和生物学评估。其中，带有4-（3-甲氧基苄氧基）苄基的化合物5c表现出最强的活性，它比奥司他韦羧酸盐（OSC）对N1（H1N1），N1（H5N1）和N1（H5N1-H274Y）的活性低或适度提高）。具体而言，针对野生型菌株H1N1的活性损失了30倍。但是5c与OSC相比，其针对H5N1-H274Y NA的活性高4.85倍。同样，5c在体外显示出低细胞毒性，在小鼠中没有急性毒性。分子对接研究提供了对5c对N1和N1-H274Y突变型NAs的高效力的见解。另外，对代表性化合物的理化性质和CYP酶抑制能力进行了计算机模拟预测，以评价其类药物性质。
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  DOI：10.1021/acs.analchem.6b02113

  日期：2016.9.20

  unwanted hydrolysis. To explore the strategies toward avoiding the hydrolysis, the detailed hydrolysis mechanism was first investigated, which was also confirmed by density functional theory (DFT) calculation. Then a series of merocyanine dyes were rationally designed. Influences of molecular structures of the probes, the analytical media such as pH and components of the solution on the hydrolysis were

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  作者：Yaqiong Kong、Rong Wu、Xiaodong Wang、Guoxu Qin、Fengyi Wu、Chunyu Wang、Minmin Chen、Nannan Wang、Qian Wang、Duojun Cao

  DOI：10.1039/d2ra04549d

  日期：——

  Fluorescent probes designed to sense and image peroxynitrite (ONOO⁻).

  用于检测和成像过亚硝酸盐（ONOO-）的荧光探针。
• A water-soluble boronate masked benzoindocyanin fluorescent probe for the detection of endogenous mitochondrial peroxynitrite in live cells and zebrafish as inflammation models
  作者：Prasad M. Sonawane、Tesla Yudhistira、Mahesh B. Halle、Arkaprava Roychaudhury、Yunsu Kim、Sachin S. Surwase、Vikas K. Bhosale、Juhyeon Kim、Hee-Sung Park、Yeu-chun Kim、Cheol-Hee Kim、David G. Churchill

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