3-氨基-5-[[[2-[(2-甲氧基乙基)氨基]-6-[4-(三氟甲基)苯基]-4-嘧啶基]氧基]-2(1H)-喹喔啉酮 | 939040-79-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 3-氨基-5-[[[2-[(2-甲氧基乙基)氨基]-6-[4-(三氟甲基)苯基]-4-嘧啶基]氧基]-2(1H)-喹喔啉酮
• 英文名称: 3-amino-5-((2-((2-methoxyethyl)amino)-6-(4-(trifluoromethyl)phenyl)pyrimidin-4-yl)oxy)quinoxalin-2(1H)-one
• 英文别名: 3-amino-5-[2-(2-methoxyethylamino)-6-[4-(trifluoromethyl)phenyl]pyrimidin-4-yl]oxy-1H-quinoxalin-2-one
• CAS: 939040-79-6
• 化学式: C₂₂H₁₉F₃N₆O₃
• 分子量: 472.426
• InChiKey: TUMYQRZCVIQKOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-amino-5-(2-chloro-6-(4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)quinoxalin-2(1H)-one 、 2-甲氧基乙胺 以 乙醇 为溶剂， 生成 3-氨基-5-[[[2-[(2-甲氧基乙基)氨基]-6-[4-(三氟甲基)苯基]-4-嘧啶基]氧基]-2(1H)-喹喔啉酮
  参考文献：
  名称：

  Design and Synthesis of Peripherally Restricted Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists

  摘要：

  Transient receptor potential vanilloid 1 (TRPV 1) channel antagonists may have clinical utility for the treatment of chronic nociceptive and neuropathic pain. We recently advanced a TRPV1 antagonist, 3 (AMG 517), into clinical trials as a new therapy for the treatment of pain. However, in addition to the desired analgesic effects, this TRPV1 antagonist significantly increased body core temperature following oral administration in rodents. Here, we, report one of our approaches to eliminate or minimize the on-target hyperthermic effect observed with this and other TRPV1 antagonists. Through modifications of our clinical candidate, 3 a series of potent and peripherally restricted TRPV1 antagonists have been prepared. These analogues demonstrated on-target coverage in vivo but caused increases in body core temperature, suggesting that peripheral restriction was not sufficient to separate antagonism mediated antihyperalgesia from hyperthermia. Furthermore, these studies demonstrate that the site of action for TRPV1 blockade elicited hyperthermia is outside the blood-brain barrier.

  DOI：

  10.1021/jm7014638

文献信息

• Fibrous Structures Comprising Sensates
  申请人：The Procter & Gamble Company

  公开号：US20180280562A1

  公开（公告）日：2018-10-04

  Fibrous structures, for example sanitary tissue products, such as toilet tissue, containing one or more sensates, more particularly one or more TRPM8 receptor triggering agents, a sensate composition, for example surface softening composition, comprising one or more TRPM8 receptor triggering agents, and methods for making same are provided.
• Method to Abate Acute Airway Hypersensitivity and Asthma Attacks
  申请人：UTI Limited Partnership

  公开号：US20200215085A1

  公开（公告）日：2020-07-09

  Methods for prevention and treatment of asthma attacks involve the administration of one or more TRPV1 antagonists, one or more LPAr antagonists or preferably a combination of one or more TRPV1 antagonists and one or more LPAr antagonists. TRPV1 antagonists and/or LPAr antagonists or a combination of both inhibit or prevent carotid body activation during an acute asthma attack. TRPV1 antagonists, LPAr antagonists or a combination thereof are useful for preventing or ameliorating the symptoms of asthma attacks. Pharmaceutical compositions for use in treating asthma and more specifically for preventing or treating asthma attacks comprise a combination of a TRPV1 antagonist and an LPAr antagonist. Methods for making medicaments for such treatment are provided. Also provided are kits for treating asthma and for preventing or treating asthma attacks in which a TRPV1 antagonist and an LPAr antagonist are separately formulated for administration at the same time.
• Design and Synthesis of Peripherally Restricted Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists
  作者：Nuria Tamayo、Hongyu Liao、Markian M. Stec、Xianghong Wang、Partha Chakrabarti、Dan Retz、Elizabeth M. Doherty、Sekhar Surapaneni、Rami Tamir、Anthony W. Bannon、Narender R. Gavva、Mark H. Norman

  DOI：10.1021/jm7014638

  日期：2008.5.1

  Transient receptor potential vanilloid 1 (TRPV 1) channel antagonists may have clinical utility for the treatment of chronic nociceptive and neuropathic pain. We recently advanced a TRPV1 antagonist, 3 (AMG 517), into clinical trials as a new therapy for the treatment of pain. However, in addition to the desired analgesic effects, this TRPV1 antagonist significantly increased body core temperature following oral administration in rodents. Here, we, report one of our approaches to eliminate or minimize the on-target hyperthermic effect observed with this and other TRPV1 antagonists. Through modifications of our clinical candidate, 3 a series of potent and peripherally restricted TRPV1 antagonists have been prepared. These analogues demonstrated on-target coverage in vivo but caused increases in body core temperature, suggesting that peripheral restriction was not sufficient to separate antagonism mediated antihyperalgesia from hyperthermia. Furthermore, these studies demonstrate that the site of action for TRPV1 blockade elicited hyperthermia is outside the blood-brain barrier.