2-(azetidin-1-yl)-4,6-dimethylpyrimidine

• 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)-4,6-dimethylpyrimidine
• 化学式: C₉H₁₃N₃
• 分子量: 163.222
• InChiKey: YNUYURLVWYMLSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(azetidin-1-yl)-4,6-dimethylpyrimidine 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 硼酸三甲酯 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 2-(azetidinyl-1-yl)-6-hexadecyl-4-methylpyrimidin-5-ol
  参考文献：
  名称：

  [EN] THERAPEUTIC COMPOUNDS
  [FR] COMPOSÉS THÉRAPEUTIQUES

  摘要：

  公开号：

  WO2016133959A9
• 作为产物：
  描述：

  2-氯-4,6-二甲基嘧啶 、 azetidine hydrochloride 在 copper(l) iodide 、 3,4,7,8-四甲基-1,10-菲罗啉 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以65%的产率得到2-(azetidin-1-yl)-4,6-dimethylpyrimidine
  参考文献：
  名称：

  Optimization of pyrimidinol antioxidants as mitochondrial protective agents: ATP production and metabolic stability

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2016.08.039

文献信息

• JANUS KINASE INHIBITOR COMPOUNDS AND METHODS
  申请人：GOODACRE SIMON CHARLES

  公开号：US20100317643A1

  公开（公告）日：2010-12-16

  The invention provides compounds of Formula I, stereoisomers or pharmaceutically acceptable salts thereof, wherein A, B, D, R 1 , R 2 , R 4 and R 5 are defined herein, a pharmaceutical composition that includes a compound of Formula I and methods of use thereof

  这项发明提供了公式I的化合物，其立体异构体或药学上可接受的盐，其中A、B、D、R1、R2、R4和R5在此处被定义，包括公式I化合物的药物组合物以及其使用方法
• [EN] SULFONYL PYRIDYL TRP INHIBITORS<br/>[FR] INHIBITEURS DE SULFONYLPYRIDYLE TRP
  申请人：HOFFMANN LA ROCHE

  公开号：WO2018029288A1

  公开（公告）日：2018-02-15

  The invention is concerned with the compounds of formula I: (I) and pharmaceutically acceptable salts thereof where R1 is a substituted or unsubstituted phenyl or a fused bicyclic comprising a substituted or unsubstituted phenyl. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

  本发明涉及公式I的化合物：(I)以及其中R1是取代的或未取代的苯基或包含取代的或未取代的苯基的并环双环的 pharmaceutically 可接受的盐。此外，本发明还涉及制造和使用公式I化合物的方法以及包含此类化合物的药物组合物。这些化合物可能对治疗由TRPA1介导的疾病和状况，如疼痛，是有用的。
• [EN] 1-(HET)ARYLSULFONYL-(PYRROLIDINE OR PIPERIDINE)-2-CARBOXAMIDE DERIVATIVES AND THEIR USE AS TRPA1 ANTAGONISTS<br/>[FR] DÉRIVÉS DE 1-(HET)ARYLSULFONYLE- (PYRROLIDINE OU PIPÉRIDINE)-2-CARBOXAMIDE ET LEUR UTILISATION COMME ANTAGONISTES DE TRPA1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2016128529A1

  公开（公告）日：2016-08-18

  The invention is concerned with the compounds of formula I and salts thereof and other compounds of formulas II-IX as disclosed herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formulas I-IX as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain or asthma.

  本发明涉及公式I的化合物及其盐，以及如本文所述的公式II-IX的其他化合物。此外，本发明还涉及制造和使用公式I-IX化合物的方法，以及含有这些化合物的药物组合物。这些化合物可能对治疗由TRPA1介导的疾病和状况，如疼痛或哮喘等有帮助。
• SUBSTITUTED SULFONAMIDE COMPOUNDS
  申请人：Genentech, Inc.

  公开号：US20160264567A1

  公开（公告）日：2016-09-15

  The invention is concerned with the compounds of formula I: and salts thereof and other compounds of formulas II-IX as disclosed herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formulas I-IX as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain or asthma.

  本发明涉及以下式子的化合物：I，并且包括其盐和其他式子II-IX的化合物，如本文所述。此外，本发明涉及制造和使用式I-IX化合物的方法，以及含有这些化合物的药物组合物。这些化合物可能对治疗由TRPA1介导的疾病和状况，例如疼痛或哮喘，有用。
• 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。