1-acetyl-5-(5-phenylpyridin-3-yl)-2,3-dihydro-1H-indole | 1593884-60-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-acetyl-5-(5-phenylpyridin-3-yl)-2,3-dihydro-1H-indole
• 英文别名: 1-[5-(5-Phenylpyridin-3-yl)-2,3-dihydroindol-1-yl]ethanone；1-[5-(5-phenylpyridin-3-yl)-2,3-dihydroindol-1-yl]ethanone
• CAS: 1593884-60-6
• 化学式: C₂₁H₁₈N₂O
• 分子量: 314.387
• InChiKey: TYNPACDMWSEFPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-乙酰-5-溴吲哚啉 在 四(三苯基膦)钯 、 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 potassium acetate 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 水 为溶剂， 反应 2.0h， 生成 1-acetyl-5-(5-phenylpyridin-3-yl)-2,3-dihydro-1H-indole
  参考文献：
  名称：

  Novel Pyridyl- or Isoquinolinyl-Substituted Indolines and Indoles as Potent and Selective Aldosterone Synthase Inhibitors

  摘要：

  Pathologically, high levels of aldosterone are associated with severe cardiovascular diseases such as congestive heart failure, hypertension, and myocardial fibrosis. The inhibition of aldosterone synthase (CYP11B2) to reduce aldosterone levels has been proposed as a promising treatment for diseases related to CYP11B2 because it is the crucial enzyme in the biosynthesis of aldosterone. A series of novel pyridyl- or isoquinolinyl-substituted indolines and indoles was designed via a ligand-based approach. The synthesized compounds were tested and found to be strong CYP11B2 inhibitors. The most potent ones showed IC50 values of less than 3 nM, being similarly potent as fadrozole and LCI699. Among them, compounds 14 and 23 showed good selectivity over the highly homologous CYP11B1, with selectivity factors (SF = IC50 CYP11B1/IC50 CYP11B2) around 170; thus, they are superior to fadrozole and LCI699 (SFs < 15). These potent CYP11B2 inhibitors exhibited no inhibition (IC50 > 50 μM) of a panel of hepatic CYP enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 and the crucial steroidogenic enzymes, CYP17 and CYP19. Because of these advantageous profiles, compounds 14 and 23 are considered to be candidates for further in vivo evaluation.

  DOI：

  10.1021/jm500140c

文献信息

• INDOLINE COMPOUNDS AS ALDOSTERONE SYNTHASE INHIBITORS
  申请人：ALI Amjad

  公开号：US20150225365A1

  公开（公告）日：2015-08-13

  This invention relates to indo line compounds of the structural formula I, or their pharmaceutically acceptable salts, wherein the variables are defined herein. The inventive compounds selectively inhibit aldosterone synthase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as potentially to methods for the treatment amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthase.

  本发明涉及结构式I的印度线化合物或其药学上可接受的盐，其中变量在此定义。这些创新化合物可选择性地抑制醛固酮合成酶。本发明还提供了包含式I化合物或其盐的制药组合物，以及可能用于治疗、改善或预防通过抑制醛固酮合成酶可治疗的疾病的方法。
• 5-PYRIDIN-3-YL-2,3-DIHYDRO-1H-INDOLE DERIVATIVES AS ALDOSTERONE SYNTHASE (CYP11B2) INHIBITORS FOR THE TREATMENT OF HYPERTENSION
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2903615B1

  公开（公告）日：2021-04-07
• INDOLINE COMPOUNDS AS ALDOSTERONE SYNTHASE INHIBITIORS RELATED APPLICATIONS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2903615A1

  公开（公告）日：2015-08-12
• US9550750B2
  申请人：——

  公开号：US9550750B2

  公开（公告）日：2017-01-24
• US9745282B2
  申请人：——

  公开号：US9745282B2

  公开（公告）日：2017-08-29