2-chloro-4-isopropoxy-6-pyrimidine | 90002-90-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-isopropoxy-6-pyrimidine
• 英文别名: 2-Chlor-4-methyl-6-isopropyloxy-pyrimidin；2-Chlor-4-isopropyloxy-6-methyl-pyrimidin；2-chloro-4-isopropoxy-6-methyl-pyrimidine；2-Chlor-4-isopropoxy-6-methyl-pyrimidin；2-Chloro-4-methyl-6-propan-2-yloxypyrimidine
• CAS: 90002-90-7
• 化学式: C₈H₁₁ClN₂O
• 分子量: 186.641
• InChiKey: XWDCCFCHMQBZTI-UHFFFAOYSA-N

物化性质

• 沸点：
  95 °C(Press: 2 Torr)
• 密度：
  1.155±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-4-isopropoxy-6-pyrimidine 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 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 为溶剂， 反应 17.67h， 生成 2-(azetidin-1-yl)-6-hexadecyl-4-isopropoxypyrimidin-5-ol
  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
• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 、 异丙醇 在 sodium hydride 作用下， 以 四氢呋喃 、 paraffin oil 为溶剂， 反应 4.5h， 生成 2-chloro-4-isopropoxy-6-pyrimidine
  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

• BIARYL DERIVATIVE AS GPR120 AGONIST
  申请人：LG Chem, Ltd.

  公开号：EP3239143A2

  公开（公告）日：2017-11-01

  The present invention relates to a biaryl derivative expressed by the chemical formula 1, a method for producing the biaryl derivative, a pharmaceutical composition comprising same, and use of same, the biaryl derivative expressed by the chemical formula 1, as a GPR120 agonist, promoting GLP-1 generation in the gastro-intestinal tract, reducing insulin resistance in the liver, muscles and the like from anti-inflammatory activity in the macrophage, pancreatic cells and the like, and allowing effective use in prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.

  本发明涉及一种由化学式1表示的生物芳基衍生物、生产该生物芳基衍生物的方法、包含该生物芳基衍生物的药物组合物以及该生物芳基衍生物的用途，由化学式1表示的生物芳基衍生物作为GPR120激动剂，促进胃肠道中GLP-1的生成、从巨噬细胞、胰腺细胞等的抗炎活性中降低肝脏、肌肉等的胰岛素抵抗，并可有效用于预防或治疗炎症或代谢性疾病，如糖尿病、糖尿病并发症、肥胖症、非酒精性脂肪肝、脂肪肝和骨质疏松症。
• Biaryl derivative as GPR120 agonist
  申请人：LG CHEM, LTD.

  公开号：US11261186B2

  公开（公告）日：2022-03-01

  Compounds having the chemical formula 1, a method for producing the compounds of chemical formula 1, a pharmaceutical composition comprising same, and use thereof as a GPR120 agonist for prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.

  具有化学式1的化合物，制备所述化学式1化合物的方法，包含所述化合物的药物组合物，以及将其用作一种GPR120激动剂，用于预防或治疗炎症或代谢性疾病，如糖尿病、糖尿病并发症、肥胖症、非酒精性脂肪肝病、脂肪肝病和骨质疏松症。
• EP3239143
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.