3-(4-piperidinyl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone | 142852-16-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 3-(4-piperidinyl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone
• 英文别名: 3-(piperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)propan-1-one；8-[1-Oxo-3-(piperidin-4-yl)propyl]-2,3,4,5-tetrahydro-1H-1-benzazepine；3-piperidin-4-yl-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)propan-1-one
• CAS: 142852-16-2
• 化学式: C₁₈H₂₆N₂O
• 分子量: 286.417
• InChiKey: NRGRZWNAVCNINV-UHFFFAOYSA-N

物化性质

• 沸点：
  475.5±38.0 °C(Predicted)
• 密度：
  1.035±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-piperidinyl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone 以76的产率得到Zanapezil fumarate
  参考文献：
  名称：

  Condensed heterocyclic compounds, their production and use

  摘要：

  一种公式（I）的缩合杂环衍生物：##STR1## 其中X是氧原子、硫原子或R.sup.1 -N<，其中R.sup.1是氢原子、可取代的碳氢基团或可取代的酰基基团；R.sup.2是氢原子或可取代的碳氢基团；环A是苯环，可取代；k是0至3的整数；m是1至8的整数；n是1至6的整数；或其药学上可接受的盐，具有高胆碱酯酶抑制活性，以及其制备方法。

  公开号：

  US05273974A1
• 作为产物：
  描述：

  3-(1-acetyl-4-piperidinyl)-1-(1-acetyl-2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone 以95的产率得到3-(4-piperidinyl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone
  参考文献：
  名称：

  Condensed heterocyclic compounds, their production and use

  摘要：

  一种公式（I）的缩合杂环衍生物：##STR1## 其中X是氧原子、硫原子或R.sup.1 -N<，其中R.sup.1是氢原子、可取代的碳氢基团或可取代的酰基基团；R.sup.2是氢原子或可取代的碳氢基团；环A是苯环，可取代；k是0至3的整数；m是1至8的整数；n是1至6的整数；或其药学上可接受的盐，具有高胆碱酯酶抑制活性，以及其制备方法。

  公开号：

  US05273974A1

文献信息

• Direct β-Alkylation of Ketones and Aldehydes via Pd-Catalyzed Redox Cascade
  作者：Chengpeng Wang、Guangbin Dong

  DOI：10.1021/jacs.8b03530

  日期：2018.5.16

  report a direct β-alkylation of ketones and aldehydes with simple alkyl bromides through a Pd-catalyzed redox-cascade strategy. The use of a Cu cocatalyst is important for improved efficiency. The reaction is redox-neutral, without the need for strong acids or bases. Both cyclic and acyclic ketones, as well as α-branched aldehydes, are suitable substrates for coupling with secondary and tertiary alkyl

  我们报告了通过 Pd 催化的氧化还原级联策略用简单的烷基溴对酮和醛进行直接 β-烷基化。铜助催化剂的使用对于提高效率很重要。该反应是氧化还原中性的，不需要强酸或强碱。环状和无环酮以及α-支化醛都是与仲和叔烷基溴偶联的合适底物。Zanapezil 的简明正式合成是使用这种 β-烷基化方法实现的。
• Central Cholinergic Agents. 6. Synthesis and Evaluation of 3-[1-(Phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)- 1-propanones and Their Analogs as Central Selective Acetylcholinesterase Inhibitors
  作者：Yuji Ishihara、Keisuke Hirai、Masaomi Miyamoto、Giichi Goto

  DOI：10.1021/jm00041a007

  日期：1994.7

  In an attempt to find central selective acetylcholinesterase (AChE) inhibitors, 3-[1-(phenyl-methyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanones 9 and their analogs were designed on the basis of our working hypothesis of the enzyme's active site. These compounds were prepared by regioselective Friedel-Crafts acylation of 2,3,4,5-tetrahydro-1H-benzazepines and related nitrogen heterocycles as a key step. Most compounds showed potent inhibitory activities with IC(50)s in the 10-300 nM range. In order to estimate their central selectivities, we examined their effects on the apomorphine-induced circling behavior in rats with unilateral striatal lesions. Among compounds with potent AChE inhibition, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (9a, TAK-147) (IC50 of AChE inhibition = 97.7 nM) inhibited the circling behavior at 3 mg/kg po, in which it had no significant effect on peripheral cholinergic effects. This demonstrates that 9a has favorable central selectivity. Furthermore, 9a significantly ameliorated diazepam-induced passive avoidance deficit at 1 mg/kg po. The benzazepine derivative 9a was selected as a candidate for clinical evaluation.
• Drugs Fut. 1995, 20, 248
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 1994, 37, 2292-2299
  作者：

  DOI：——

  日期：——
• US5273974A
  申请人：——

  公开号：US5273974A

  公开（公告）日：1993-12-28