tert-butyl (6-((diethylamino)methyl)-5-hydroxynaphthalen-1-yl)carbamate | 1630086-22-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl (6-((diethylamino)methyl)-5-hydroxynaphthalen-1-yl)carbamate
• 英文别名: tert-butyl N-[6-(diethylaminomethyl)-5-hydroxynaphthalen-1-yl]carbamate
• CAS: 1630086-22-4
• 化学式: C₂₀H₂₈N₂O₃
• 分子量: 344.454
• InChiKey: HUJVIXVNRMGGAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (6-((diethylamino)methyl)-5-hydroxynaphthalen-1-yl)carbamate 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 生成 tert-butyl (5-hydroxy-6-methylnaphthalen-1-yl)carbamate
  参考文献：
  名称：

  [EN] PYRIMIDINYL-PYRIDYLOXY-NAPHTHYL COMPOUNDS AND METHODS OF TREATING IRE1-RELATED DISEASES AND DISORDERS
  [FR] COMPOSÉS PYRIMIDINYL-PYRIDYLOXY-NAPHTYLE ET PROCÉDÉS DE TRAITEMENT DE MALADIES ET DE TROUBLES LIÉS À IRE1

  摘要：

  本文描述了具有肌醇需要酶1（IRE1）调节活性或功能的嘧啶基-吡啶氧基-萘基化合物，其具有公式（I）或（I'）结构：或其立体异构体，互变异构体或药学上可接受的盐，并具有所述的取代基和结构特征。还描述了包括公式（I）或（I'）化合物的制药组合物和药物，以及使用这种IRE1调节剂的方法，单独或与其他治疗剂联合治疗介导或依赖于雌激素受体的疾病或病况。

  公开号：

  WO2018166528A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 4.5h， 生成 tert-butyl (6-((diethylamino)methyl)-5-hydroxynaphthalen-1-yl)carbamate
  参考文献：
  名称：

  [EN] PYRIMIDINYL-PYRIDYLOXY-NAPHTHYL COMPOUNDS AND METHODS OF TREATING IRE1-RELATED DISEASES AND DISORDERS
  [FR] COMPOSÉS PYRIMIDINYL-PYRIDYLOXY-NAPHTYLE ET PROCÉDÉS DE TRAITEMENT DE MALADIES ET DE TROUBLES LIÉS À IRE1

  摘要：

  本文描述了具有肌醇需要酶1（IRE1）调节活性或功能的嘧啶基-吡啶氧基-萘基化合物，其具有公式（I）或（I'）结构：或其立体异构体，互变异构体或药学上可接受的盐，并具有所述的取代基和结构特征。还描述了包括公式（I）或（I'）化合物的制药组合物和药物，以及使用这种IRE1调节剂的方法，单独或与其他治疗剂联合治疗介导或依赖于雌激素受体的疾病或病况。

  公开号：

  WO2018166528A1

文献信息

• Pyrimidinyl-pyridyloxy-naphthyl compounds and methods of treating IRE1-related diseases and disorders
  申请人：Genentech, Inc.

  公开号：US10968203B2

  公开（公告）日：2021-04-06

  Described herein are pyrimidinyl-pyridyloxy-naphthyl compounds with inositol requiring enzyme 1 (IRE1) modulation activity or function having the Formula I or I′ structure: or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I or I′ compounds, as well as methods of using such IRE1 modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

  这里描述的是具有式 I 或 I′结构的嘧啶基吡啶氧基萘化合物，它们具有调节肌醇需要酶 1（IRE1）的活性或功能： 或其立体异构体、同系物或药学上可接受的盐，并具有本文所述的取代基和结构特征。还描述了包括式Ⅰ或Ⅰ′化合物的药物组合物和药物，以及单独或与其它治疗剂联合使用这种IRE1调节剂治疗由雌激素受体介导或依赖于雌激素受体的疾病或病症的方法。
• Unfolded Protein Response in Cancer: IRE1α Inhibition by Selective Kinase Ligands Does Not Impair Tumor Cell Viability
  作者：Paul E. Harrington、Kaustav Biswas、David Malwitz、Andrew S. Tasker、Christopher Mohr、Kristin L. Andrews、Ken Dellamaggiore、Richard Kendall、Holger Beckmann、Peter Jaeckel、Silvia Materna-Reichelt、Jennifer R. Allen、J. Russell Lipford

  DOI：10.1021/ml500315b

  日期：2015.1.8

  The kinase/endonuclease inositol requiring enzyme 1 (IRE1 alpha), one of the sensors of unfolded protein accumulation in the endoplasmic reticulum that triggers the unfolded protein response (UPR), has been investigated as an anticancer target. We identified potent allosteric inhibitors of IRE1 alpha endonuclease activity that bound to the kinase site on the enzyme. Structure-activity relationship (SAR) studies led to 16 and 18, which were selective in kinase screens and were potent against recombinant IRE1 alpha endonuclease as well as cellular IRE1 alpha. The first X-ray crystal structure of a kinase inhibitor (16) bound to hIRE1 alpha was obtained. Screening of native tumor cell lines (>300) against selective IRE1 alpha inhibitors failed to demonstrate any effect on cellular viability. These results suggest that IRE1 alpha activity is not essential for viability in most tumor cell lines, in vitro, and that interfering with the survival functions of the UPR may not be an effective strategy to block tumorigenesis.
• PYRIMIDINYL-PYRIDYLOXY-NAPHTHYL COMPOUNDS AND METHODS OF TREATING IRE1-RELATED DISEASES AND DISORDERS
  申请人：Genentech, Inc.

  公开号：US20180265497A1

  公开（公告）日：2018-09-20

  Described herein are pyrimidinyl-pyridyloxy-naphthyl compounds with inositol requiring enzyme 1 (IRE1) modulation activity or function having the Formula I or I′ structure: or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I or I′ compounds, as well as methods of using such IRE1 modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.