2-(azetidin-1-yl)-4-cyclobutoxy-6-hexadecylpyrimidin-5-ol

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(azetidin-1-yl)-4-cyclobutoxy-6-hexadecylpyrimidin-5-ol
• 英文别名: 2-(Azetidin-1-yl)-4-cyclobutyloxy-6-hexadecylpyrimidin-5-ol；2-(azetidin-1-yl)-4-cyclobutyloxy-6-hexadecylpyrimidin-5-ol
• 化学式: C₂₇H₄₇N₃O₂
• 分子量: 445.689
• InChiKey: JWKXOOQHCNSWGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.9
• 重原子数：
  32
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  58.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 sodium hydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 paraffin oil 为溶剂， 反应 22.59h， 生成 2-(azetidin-1-yl)-4-cyclobutoxy-6-hexadecylpyrimidin-5-ol
  参考文献：
  名称：

  [EN] THERAPEUTIC COMPOUNDS
  [FR] COMPOSÉS THÉRAPEUTIQUES

  摘要：

  公开号：

  WO2016133959A9

文献信息

• Influence of substituent heteroatoms on the cytoprotective properties of pyrimidinol antioxidants
  作者：Arnaud Chevalier、Omar M. Khdour、Margaret Schmierer、Indrajit Bandyopadhyay、Sidney M. Hecht

  DOI：10.1016/j.bmc.2017.01.030

  日期：2017.3

  vitro using bovine liver microsomes. Unexpectedly, the 2-alkoxy-4-alkylamino substituted pyrimidinol antioxidants were found to have properties in protecting mitochondrial function superior to the isomeric 4-alkoxy-2-alkylamino substituted pyrimidinols evaluated in all earlier studies. This observation suggests a possible mode of action involving the intermediacy of an ortho-iminoquinone, a species not

  最近，我们描述了新型基于嘧啶醇的抗氧化剂的优化，作为针对线粒体疾病的潜在治疗分子。该研究的重点是提高嘧啶醇抗氧化剂的效力和代谢稳定性。这使我们考虑了改变嘧啶醇支架上环外烷氧基和烷基氨基取代基位置的可能性。制备了十二种新的类似物，并对其生物学活性进行了研究。体外还评估了制备的区域异构体的代谢稳定性使用牛肝微粒体。出乎意料的是，发现2-烷氧基-4-烷基氨基取代的嘧啶醇抗氧化剂具有保护线粒体功能的特性，优于所有早期研究中评估的异构体4-烷氧基-2-烷基氨基取代的嘧啶醇。该观察结果提示了可能涉及的作用方式包括邻亚氨基亚醌，该亚氨基以前与线粒体呼吸链功能不相关。
• PHARMACEUTICAL COMPOSITIONS COMPRISING DEUTERATED AND UNDEUTERATED 2-AMINO-PYRIMIDIN-5-OL DERIVATIVES FOR TREATING MITOCHONDRIAL DISEASES (E.G. OBESITY)
  申请人：Arizona Board of Regents on behalf of Arizona State University

  公开号：EP3719006A1

  公开（公告）日：2020-10-07

  Pharmaceutical compositions comprising Compounds of formula I and salts thereof are disclosed. Also disclosed are isotopes of compounds of formula I of the salts thereof, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods using a compound of formula I or a pharmaceutical composition thereof.

  由式 I 化合物组成的药物组合物 及其盐类组成的药物组合物。 还公开了式 I 化合物及其盐的同位素、制备式 I 化合物的工艺、制备式 I 化合物的中间体以及使用式 I 化合物或其药物组合物的治疗方法。
• Therapeutic compounds
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US10364227B2

  公开（公告）日：2019-07-30

  Compounds of formula (I) and salts are disclosed. Also disclosed are isotopes of compounds of formula I of the salts thereof. Pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods using a compound of formula I are disclosed.

  公开了式 (I) 化合物及其盐类。还公开了式 I 化合物的同位素及其盐类。公开了包含式 I 化合物的药物组合物、制备式 I 化合物的工艺、用于制备式 I 化合物的中间体以及使用式 I 化合物的治疗方法。
• Substituted pyrimidine compounds as multifunctional radical quenchers and their uses
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US11390605B2

  公开（公告）日：2022-07-19

  The invention provides compounds having the general formula I: and pharmaceutically acceptable salts thereof, wherein the variables R1, R2, R3 and R4 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

  本发明提供了具有通式 I：的化合物及其药学上可接受的盐类，其中变量 R1、R2、R3 和 R4 的含义如本文所述，还提供了含有此类化合物的组合物以及使用此类化合物和组合物的方法。
• Optimization of pyrimidinol antioxidants as mitochondrial protective agents: ATP production and metabolic stability
  作者：Arnaud Chevalier、Mohammad Parvez Alam、Omar M. Khdour、Margaret Schmierer、Pablo M. Arce、Cameron D. Cripe、Sidney M. Hecht

  DOI：10.1016/j.bmc.2016.08.039

  日期：2016.11

  Previously we described a novel series of pyrimidinol antioxidants and their structural optimization as potential therapeutic agents for neurodegenerative and mitochondrial disorders. Our initial lead compound was a potent antioxidant in vitro, but was subsequently found to exhibit poor stability to oxidative metabolism. The current study focused on balancing potency with metabolic stability through structural modification, and involved modifications at positions 2 and 4 of the pyrimidinol redox core, likely sites of oxidative metabolism. Eight new analogues have been prepared and their ability to suppress lipid peroxidation and reactive oxygen species (ROS), and to preserve mitochondrial membrane potential (Delta psi(m)) and support ATP production, has been investigated. The metabolic stability of the prepared compounds was also assessed in vitro using bovine liver microsomes to obtain preliminary insight on this class of compounds. This study revealed the complexity of balancing reasonable metabolic stability with efficient antioxidant properties. While a few analogues appear promising, especially in terms of metabolic stability, a 4-isopropoxy derivative conserved the favorable biological activity and exhibited good metabolic stability. The favorable metabolic stability conferred by the combination of the azetidine and isopropoxy moieties in analogue 6 makes this compound an excellent candidate for further evaluation. (C) 2016 Elsevier Ltd. All rights reserved.