4-chloro-N,N-diethyl-6-[(2,2,3,3,-tetrafluoropropan)oxy]-1,3,5-triazin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 4-chloro-N,N-diethyl-6-[(2,2,3,3,-tetrafluoropropan)oxy]-1,3,5-triazin-2-amine
• 英文别名: 4-chloro-N,N-diethyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazin-2-amine
• 化学式: C₁₀H₁₃ClF₄N₄O
• 分子量: 316.686
• InChiKey: YPGJIOCUVIXAOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-chloro-N,N-diethyl-6-[(2,2,3,3,-tetrafluoropropan)oxy]-1,3,5-triazin-2-amine 、 间氨基苯甲酸 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以60%的产率得到3-{[4-(diethylamino)-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazin-2-yl]amino}benzoic acid
  参考文献：
  名称：

  Nanomolar-Potency Aminophenyl-1,3,5-triazine Activators of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel for Prosecretory Therapy of Dry Eye Diseases

  摘要：

  Dry eye disorders are a significant health problem for which limited therapeutic options are available. CFTR is a major prosecretory chloride channel at the ocular surface. We previously identified, by high-throughput screening, aminophenyl-1,3,5-triazine CFTRact-K089 (1) that activated CFTR with EC50 approximate to 250 nM, which when delivered topically increased tear fluid secretion in mice and showed efficacy in an experimental dry eye model. Here, functional analysis of aminophenyl-1,3,5-triazine analogs elucidated structure-activity relationships for CFTR activation and identified substantially more potent analogs than 1. The most potent compound, 12, fully activated CFTR chloride conductance with EC50 approximate to 30 nM, without causing cAMP or calcium elevation. 12 was rapidly metabolized by hepatic microsomes, which supports its topical use. Single topical administration of 25 pmol of 12 increased tear volume in wild-type mice with sustained action for 8 h and was without effect in CFTR-deficient mice. Topically delivered 12 may be efficacious in human dry eye diseases.

  DOI：

  10.1021/acs.jmedchem.6b01792
• 作为产物：
  描述：

  二乙胺 、 2,4-dichloro-6-[(2,2,3,3-tetrafluoropropan)oxy]-1,3,5-triazine 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以57%的产率得到4-chloro-N,N-diethyl-6-[(2,2,3,3,-tetrafluoropropan)oxy]-1,3,5-triazin-2-amine
  参考文献：
  名称：

  [EN] CFTR REGULATORS AND METHODS OF USE THEREOF
  [FR] RÉGULATEURS CFTR ET LEURS MÉTHODES D'UTILISATION

  摘要：

  本文提供了激活CFTR的化合物以及治疗便秘、干眼症和其他疾病和障碍的方法。

  公开号：

  WO2017112951A1

文献信息

• [EN] CFTR REGULATORS AND METHODS OF USE THEREOF<br/>[FR] RÉGULATEURS CFTR ET LEURS MÉTHODES D'UTILISATION
  申请人：UNIV CALIFORNIA

  公开号：WO2017112951A1

  公开（公告）日：2017-06-29

  Provided herein are compounds that activate CFTR and methods for treating constipation, dry eye disorders, and other diseases and disorders.

  本文提供了激活CFTR的化合物以及治疗便秘、干眼症和其他疾病和障碍的方法。
• CFTR regulators and methods of use thereof
  申请人：The Regents of the University of California

  公开号：US10604492B2

  公开（公告）日：2020-03-31

  Provided herein are compounds that activate CFTR and methods for treating constipation, dry eye disorders, and other diseases and disorders.

  本文提供了激活 CFTR 的化合物和治疗便秘、干眼症及其他疾病和失调的方法。
• CFTR REGULATORS AND METHODS OF USE THEREOF
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP3394040B1

  公开（公告）日：2021-12-22
• Nanomolar-Potency Aminophenyl-1,3,5-triazine Activators of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel for Prosecretory Therapy of Dry Eye Diseases
  作者：Sujin Lee、Puay-Wah Phuan、Christian M. Felix、Joseph-Anthony Tan、Marc H. Levin、Alan S. Verkman

  DOI：10.1021/acs.jmedchem.6b01792

  日期：2017.2.9

  Dry eye disorders are a significant health problem for which limited therapeutic options are available. CFTR is a major prosecretory chloride channel at the ocular surface. We previously identified, by high-throughput screening, aminophenyl-1,3,5-triazine CFTRact-K089 (1) that activated CFTR with EC50 approximate to 250 nM, which when delivered topically increased tear fluid secretion in mice and showed efficacy in an experimental dry eye model. Here, functional analysis of aminophenyl-1,3,5-triazine analogs elucidated structure-activity relationships for CFTR activation and identified substantially more potent analogs than 1. The most potent compound, 12, fully activated CFTR chloride conductance with EC50 approximate to 30 nM, without causing cAMP or calcium elevation. 12 was rapidly metabolized by hepatic microsomes, which supports its topical use. Single topical administration of 25 pmol of 12 increased tear volume in wild-type mice with sustained action for 8 h and was without effect in CFTR-deficient mice. Topically delivered 12 may be efficacious in human dry eye diseases.