(9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid | 1464115-37-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 英文名称: (9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid
• 英文别名: 9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl boronic acid；(9-Fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid
• CAS: 1464115-37-4
• 化学式: C₁₁H₁₁BFN₃O₂
• 分子量: 247.037
• InChiKey: REUGLGSLWRNTNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.51
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-溴异喹啉 、 (9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid 在 四丁基溴化铵 、 palladium diacetate 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 以86%的产率得到9-fluoro-7-isoquinolin-4-yl-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline
  参考文献：
  名称：

  Novel Pyridyl Substituted 4,5-Dihydro-[1,2,4]triazolo[4,3-a]quinolines as Potent and Selective Aldosterone Synthase Inhibitors with Improved in Vitro Metabolic Stability

  摘要：

  CYP11B2 inhibition is a promising treatment for diseases caused by excessive aldosterone. To improve the metabolic stability in human liver miscrosomes of previously reported CYP11B2 inhibitors, modifications were performed via a combination of ligand- and structure-based drug design approaches, leading to pyridyl 4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolones. Compound 26 not only exhibited a much longer half-life (t(1/2) >> 120 min), but also sustained inhibitory potency (IC50 = 4.2 nM) and selectivity over CYP11B1 (SF = 422), CYP17, CYP19, and a panel of hepatic CYP enzymes.

  DOI：

  10.1021/acs.jmedchem.5b00079
• 作为产物：
  描述：

  8-氟-3,4-二氢-1H-喹啉-2-酮 在 劳森试剂 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 、 甲苯 、 正丁醇 为溶剂， 反应 39.0h， 生成 (9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid
  参考文献：
  名称：

  [EN] ALDOSTERONE SYNTHASE INHIBITORS
  [FR] INHIBITEURS D'ALDOSTÉRONE SYNTHASE

  摘要：

  本发明涉及三环三唑化合物或其药用盐。这些创新化合物选择性抑制醛固酮合成酶。本发明还提供了包括上述化合物或其盐的药物组合物，以及可能用于通过抑制醛固酮合成酶治疗、改善或预防可通过抑制醛固酮合成酶治疗的疾病的方法。

  公开号：

  WO2013151876A1

文献信息

• Aldosterone synthase inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US09278093B2

  公开（公告）日：2016-03-08

  This invention relates to tricyclic triazole compounds or their pharmaceutically acceptable salts. The inventive compounds selectively inhibit aldosterone synthetase. This invention also provides for pharmaceutical compositions comprising the above-cited compounds or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthetase.

  本发明涉及三环三唑化合物或其药学上可接受的盐。这些创新化合物可以选择性地抑制醛固酮合成酶。本发明还提供了包含上述化合物或其盐的药物组合物，以及可能用于抑制醛固酮合成酶治疗、改善或预防相关疾病的方法。
• ALDOSTERONE SYNTHASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20150306091A1

  公开（公告）日：2015-10-29

  This invention relates to tricyclic triazole compounds or their pharmaceutically acceptable salts. The inventive compounds selectively inhibit aldosterone synthetase. This invention also provides for pharmaceutical compositions comprising the above-cited compounds or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthetase.

  本发明涉及三环三唑化合物或其药学上可接受的盐。这些创新化合物能够选择性地抑制醛固酮合成酶。本发明还提供了包含上述化合物或其盐的制药组合物，以及用于治疗、改善或预防可以通过抑制醛固酮合成酶来治疗的疾病的方法。
• Novel Pyridyl Substituted 4,5-Dihydro-[1,2,4]triazolo[4,3-<i>a</i>]quinolines as Potent and Selective Aldosterone Synthase Inhibitors with Improved in Vitro Metabolic Stability
  作者：Qingzhong Hu、Lina Yin、Amjad Ali、Andrew J. Cooke、Jonathan Bennett、Paul Ratcliffe、Michael Man-Chu Lo、Edward Metzger、Scott Hoyt、Rolf W. Hartmann

  DOI：10.1021/acs.jmedchem.5b00079

  日期：2015.3.12

  CYP11B2 inhibition is a promising treatment for diseases caused by excessive aldosterone. To improve the metabolic stability in human liver miscrosomes of previously reported CYP11B2 inhibitors, modifications were performed via a combination of ligand- and structure-based drug design approaches, leading to pyridyl 4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolones. Compound 26 not only exhibited a much longer half-life (t(1/2) >> 120 min), but also sustained inhibitory potency (IC50 = 4.2 nM) and selectivity over CYP11B1 (SF = 422), CYP17, CYP19, and a panel of hepatic CYP enzymes.
• [EN] ALDOSTERONE SYNTHASE INHIBITORS<br/>[FR] INHIBITEURS D'ALDOSTÉRONE SYNTHASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2013151876A1

  公开（公告）日：2013-10-10

  This invention relates to tricyclic triazole compounds or their pharmaceutically acceptable salts. The inventive compounds selectively inhibit aldosterone synthetase. This invention also provides for pharmaceutical compositions comprising the above-cited compounds or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthetase.

  本发明涉及三环三唑化合物或其药用盐。这些创新化合物选择性抑制醛固酮合成酶。本发明还提供了包括上述化合物或其盐的药物组合物，以及可能用于通过抑制醛固酮合成酶治疗、改善或预防可通过抑制醛固酮合成酶治疗的疾病的方法。