AA147

• 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: AA147
• 英文别名: N-(2-hydroxy-5-methylphenyl)-3-phenylpropanamide
• 化学式: C₁₆H₁₇NO₂
• 分子量: 255.316
• InChiKey: AWHLTHOHBAGPMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  AA147 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 0.17h， 以25%的产率得到N-(2-hydroxy-5-methylphenyl)-N-methyl-3-phenylpropanamide
  参考文献：
  名称：

  Metabolically Activated Proteostasis Regulators Protect against Glutamate Toxicity by Activating NRF2

  摘要：

  DOI：

  10.1021/acschembio.1c00810
• 作为产物：
  描述：

  N-[5-methyl-2-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methoxy]phenyl]-3-phenylpropanamide 在 氧气 、 亚甲兰 作用下， 以 aq. buffer 为溶剂， 以80 %的产率得到AA147
  参考文献：
  名称：

  通过苯基自由基机制光激活硼酸前药：以铱 (III) 抗癌复合物为例

  摘要：

  硼酸（或酯）是一种众所周知的临时掩蔽基团，用于开发对肿瘤活性氧（ROS）有反应的抗癌前药，但其临床应用在很大程度上受到低活化效率的阻碍。在此，我们报告了一种强大的光激活方法，可以在低氧肿瘤微环境下时空将硼酸笼状铱 (III) 复合物IrBA转化为具有生物活性的IrNH 2 。机理研究表明， IrBA中的苯基硼酸部分与苯基硼酸阴离子处于平衡状态，该阴离子可被光氧化产生苯基自由基，苯基自由基是一种高活性物质，能够在极低浓度（低至 0.02%）下快速捕获 O 2 ). 结果，虽然IrBA很难被癌细胞中的固有 ROS 激活，在光照射下，即使在有限的 O 2供应下，前药也能有效地转化为IrNH 2，同时直接损伤线粒体 DNA 和缺氧 2D 单层细胞中的有效抗肿瘤活性，3D 肿瘤球体和携带肿瘤异种移植物的小鼠。值得注意的是，光激活方法可以扩展到通过具有红色吸收的外部光敏剂进行分子间光催化激活，并激活临

  DOI：

  10.1021/jacs.3c00254

文献信息

• Regulators of the endoplasmic reticulum proteostasis network
  申请人：The Scripps Research Institute

  公开号：US11135186B2

  公开（公告）日：2021-10-05

  The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.

  本发明提供了用于激活细胞内质网中未折叠蛋白反应（UPR）的激活转录因子6（ATF6）臂或激活ATF6的转录靶标的化合物，所述化合物为本文所述的式(I)至式(IX)中的任何一种。这些化合物可用于治疗涉及毒性功能增益和功能丧失折叠障碍的疾病，包括溶酶体贮积疾病、抗胰蛋白酶相关性肺气肿和类似疾病。这些分子还有望对阿尔茨海默病和糖尿病产生疾病改善作用。
• METHODS FOR MITIGATING AND PREVENTING PROTEOSTASIS-BASED INJURIES
  申请人：San Diego State University (SDSU) Foundation, dba San Diego State University Research Foundation

  公开号：US20210093591A1

  公开（公告）日：2021-04-01

  Provided are pharmaceutical compositions, formulations, products of manufacture and kits, and methods, for: mitigating, ameliorating, treating or preventing a proteostasis-based injury; selectively inducing only the ATF6 arm of the unfolded protein response in a cell, a tissue or in a mammal, wherein optionally the mammal is a human; protecting a mammalian heart or a mammalian tissue from an acute or a long term ischemia/reperfusion injury or damage; pharmacologically activating ATF6 or the ATF6 arm of the unfolded protein response in a cell or in vivo; comprising: administering to the cell, the tissue, the mammal or the individual in need thereof: (a) a compound as provided herein, for example, the exemplary compound 147.
• Regulators of the Endoplasmic Reticulum Proteostasis Network
  申请人：The Scripps Research Institute

  公开号：US20210393557A1

  公开（公告）日：2021-12-23

  The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.