{1-[(5-methyl-1H-indol-2-yl)carbonyl]piperidin-4-yl}acetic acid | 1449664-32-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: {1-[(5-methyl-1H-indol-2-yl)carbonyl]piperidin-4-yl}acetic acid
• 英文别名: 2-[1-(5-methyl-1H-indole-2-carbonyl)piperidin-4-yl]acetic acid
• CAS: 1449664-32-7
• 化学式: C₁₇H₂₀N₂O₃
• 分子量: 300.357
• InChiKey: QSTRMHABOYMJLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  73.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl {1-[(5-methyl-1H-indol-2-yl)carbonyl]piperidin-4-yl}acetate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 14.0h， 以69%的产率得到{1-[(5-methyl-1H-indol-2-yl)carbonyl]piperidin-4-yl}acetic acid
  参考文献：
  名称：

  Discovery of 2-methyl-1-{1-[(5-methyl-1H-indol-2-yl)carbonyl]piperidin-4-yl}propan-2-ol: A novel, potent and selective type 5 17β-hydroxysteroid dehydrogenase inhibitor

  摘要：

  Type 5 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD5), also known as aldo-keto reductase 1C3 (AKR1C3), is a member of the aldo-keto reductase superfamily of enzymes and is expressed in the human prostate. One of the main functions of 17 beta-HSD5 is to catalyze the conversion of the weak androgen, androstenedione, to the potent androgen, testosterone. The concentration of intraprostatic 5 alpha-dihydrotestosterone (DHT) in patients following chemical or surgical castration has been reported to remain as high as 39% of that of healthy men, with 17 beta-HSD5 shown to be involved in this androgen synthesis. Inhibition of 17 beta-HSD5 therefore represents a promising target for the treatment of castration-resistant prostate cancer (CRPC). To investigate this, we conducted high-throughput screening (FITS) and identified compound 2, which displayed a structure distinct from known 17 beta-HSD5 inhibitors. To optimize the inhibitory activity of compound 2, we first introduced a primary alcohol group. We then converted the primary alcohol group to a tertiary alcohol, which further enhanced the inhibitory activity, improved metabolic stability, and led to the identification of compound 17. Oral administration of compound 17 to castrated nude mice bearing the CWR22R xenograft resulted in the suppression of androstenedione (AD)-induced intratumoral testosterone production. Compound 17 also demonstrated good isoform selectivity, minimal inhibitory activity against either CYP or hERG, and enhanced pharmacokinetic and physicochemical properties. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.025