2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)-6-(trifluoromethyl)benzo[d]thiazole hydrochloride | 960534-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)-6-(trifluoromethyl)benzo[d]thiazole hydrochloride
• 英文别名: 2-[2-(Pyridin-3-yloxymethyl)piperazin-1-yl]-6-(trifluoromethyl)-1,3-benzothiazole;hydrochloride；2-[2-(pyridin-3-yloxymethyl)piperazin-1-yl]-6-(trifluoromethyl)-1,3-benzothiazole;hydrochloride
• CAS: 960534-55-8
• 化学式: C₁₈H₁₇F₃N₄OS*ClH
• 分子量: 430.881
• InChiKey: YWMKQBCXYCJZEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.99
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.5
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tert-butyl 3-((pyridin-3-yloxy)methyl)-4-(6-(trifluoromethyl)benzo[d]thiazol-2-yl)piperazine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 1.0h， 以62 mg的产率得到2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)-6-(trifluoromethyl)benzo[d]thiazole hydrochloride
  参考文献：
  名称：

  Discovery of Novel 2-((Pyridin-3-yloxy)methyl)piperazines as α7 Nicotinic Acetylcholine Receptor Modulators for the Treatment of Inflammatory Disorders

  摘要：

  Herein we report the design, synthesis, and structure activity relationships for a new class of alpha 7 nicotinic acetylcholine receptor (nAChR) modulators based on the 2-((pyridin-3-yloxy)methyl)piperazine scaffold. The oxazolo[4,5-b]pyridine, (R)-18, and 4-methoxyphenylurea, (R)-47, were identified as potent and selective modulators of the alpha 7 nAChR with favorable in vitro safety profiles and good oral bioavailability in mouse. Both compounds were shown to significantly inhibit cellular infiltration in a murine model of allergic lung inflammation. Despite the structural and in vivo functional similarities in the compounds, only (R)-18 was shown to be an agonist. Compound (R)-47 demonstrated silent agonist activity. These data support the hypothesis that the anti-inflammatory activity of the alpha 7 nAChR is mediated by a signal transduction pathway that is independent of ion current.

  DOI：

  10.1021/jm5004599

文献信息

• NOVEL PIPERAZINES, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF
  申请人：Cornerstone Therapeutics Inc.

  公开号：EP2044038B1

  公开（公告）日：2014-07-02
• Discovery of Novel 2-((Pyridin-3-yloxy)methyl)piperazines as α7 Nicotinic Acetylcholine Receptor Modulators for the Treatment of Inflammatory Disorders
  作者：Roger B. Clark、Diana Lamppu、Lyn Libertine、Amy McDonough、Anjali Kumar、Greg LaRosa、Roger Rush、Daniel Elbaum

  DOI：10.1021/jm5004599

  日期：2014.5.22

  Herein we report the design, synthesis, and structure activity relationships for a new class of alpha 7 nicotinic acetylcholine receptor (nAChR) modulators based on the 2-((pyridin-3-yloxy)methyl)piperazine scaffold. The oxazolo[4,5-b]pyridine, (R)-18, and 4-methoxyphenylurea, (R)-47, were identified as potent and selective modulators of the alpha 7 nAChR with favorable in vitro safety profiles and good oral bioavailability in mouse. Both compounds were shown to significantly inhibit cellular infiltration in a murine model of allergic lung inflammation. Despite the structural and in vivo functional similarities in the compounds, only (R)-18 was shown to be an agonist. Compound (R)-47 demonstrated silent agonist activity. These data support the hypothesis that the anti-inflammatory activity of the alpha 7 nAChR is mediated by a signal transduction pathway that is independent of ion current.