1-(2-acetyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)-3-(1-benzylpiperidin-4-yl)-propan-1-one | 263248-20-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(2-acetyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)-3-(1-benzylpiperidin-4-yl)-propan-1-one
• 英文别名: 1-(2-Acetyl-1,3,4,5-tetrahydro-2-benzazepin-8-yl)-3-(1-benzylpiperidin-4-yl)propan-1-one
• CAS: 263248-20-0
• 化学式: C₂₇H₃₄N₂O₂
• 分子量: 418.579
• InChiKey: KDWSERRHWXZVSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-acetyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)-3-(1-benzylpiperidin-4-yl)-propan-1-one 在 盐酸 作用下， 反应 12.0h， 以88%的产率得到3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one dihydrochloride
  参考文献：
  名称：

  新型乙酰胆碱酯酶抑制剂作为有节律性膀胱收缩的增强剂：SAR的8- {3- [1-（3-氟苄基）哌啶-4-基]丙酰基} -1,2,5,6-四氢-4H-吡咯[3] ，2,1-ij]喹啉-4-酮（TAK-802）和相关化合物。

  摘要：

  作为开发有节奏的膀胱收缩增加剂的正在进行的研究的一部分，合成了1-芳基-3-（1-苄基哌啶-4-基）丙烷，并将其作为非氨基甲酸酯乙酰胆碱酯酶（AChE）抑制剂进行了研究。在具有各种芳基的化合物中，发现1,2,5,6-四氢-4H-吡咯并[3,2,1-ij]喹啉-4-酮衍生物9c具有有效的AChE抑制活性，且具有IC（50 ）值1.3nM。化合物9c可增加豚鼠和大鼠的节律性膀胱收缩，而不会影响基础膀胱内压力，这表明9c可用于治疗逼尿肌功能不足引起的排尿功能障碍。

  DOI：

  10.1016/j.bmc.2005.01.022
• 作为产物：
  描述：

  3-[1-(acetyl)-4-piperidinyl]propionic acid 在 盐酸 、 sodium hydroxide 、 三氯化铝 、 氯化亚砜 、 碘代三甲硅烷 、 potassium carbonate 作用下， 以 乙醇 、 氯仿 、 1,2-二氯乙烷 为溶剂， 反应 37.0h， 生成 1-(2-acetyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)-3-(1-benzylpiperidin-4-yl)-propan-1-one
  参考文献：
  名称：

  Regioselective Friedel–Crafts acylation of 2,3,4,5-tetrahydro-1H-2-benzazepine and related nitrogen heterocycles

  摘要：

  It is revealed that NH-protected 2,3,4,5-tetrahydro-1H-2-benzazepine 4 is acylated on C-8 with greater than 95% regioselectivity. This regioselectivity has been applied to the synthesis of 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one 3a, an inhibitor of acetylcholinesterase (AChE). The regioselectivities of the acylation of the following nitrogen heterocycles have also been studied: 4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepine 6, 2,3,4,5-tetrahydro-1H-2-benzazepin-3-one 7, 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one 8, 7,11b,12,13-tetrahydro-5H-isoindolo[2,1-b][2] benzazepin-7-one 9 and 6,7,9,13b-tetrahydro-5H-isoindolo[1,2-a][2]benzazepin-9-one 10. A molecular orbital (MO) calculation on the Lewis acid coordinated substrates has been used for predicting regioselectivity.

  DOI：

  10.1039/p19940002993

文献信息

• Novel acetylcholinesterase inhibitor as increasing agent on rhythmic bladder contractions: SAR of 8-{3-[1-(3-fluorobenzyl)piperidin-4-yl]propanoyl}-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (TAK-802) and related compounds
  作者：Yuji Ishichi、Mitsuru Sasaki、Masaki Setoh、Tetsuya Tsukamoto、Seiji Miwatashi、Hiroshi Nagabukuro、Satoshi Okanishi、Shigemitsu Imai、Reiko Saikawa、Takayuki Doi、Yuji Ishihara

  DOI：10.1016/j.bmc.2005.01.022

  日期：2005.3

  As part of an on-going investigation to develop an increasing agent on rhythmic bladder contractions, 1-aryl-3-(1-benzylpiperidin-4-yl)propanones were synthesized and examined as noncarbamate acetylcholinesterase (AChE) inhibitors. Among compounds with various aryl groups, 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one derivative 9c was found to possess a potent AChE inhibition activity with

  作为开发有节奏的膀胱收缩增加剂的正在进行的研究的一部分，合成了1-芳基-3-（1-苄基哌啶-4-基）丙烷，并将其作为非氨基甲酸酯乙酰胆碱酯酶（AChE）抑制剂进行了研究。在具有各种芳基的化合物中，发现1,2,5,6-四氢-4H-吡咯并[3,2,1-ij]喹啉-4-酮衍生物9c具有有效的AChE抑制活性，且具有IC（50 ）值1.3nM。化合物9c可增加豚鼠和大鼠的节律性膀胱收缩，而不会影响基础膀胱内压力，这表明9c可用于治疗逼尿肌功能不足引起的排尿功能障碍。
• Regioselective Friedel–Crafts acylation of 2,3,4,5-tetrahydro-1H-2-benzazepine and related nitrogen heterocycles
  作者：Yuji Ishihara、Toshimasa Tanaka、Seiji Miwatashi、Akira Fujishima、Giichi Goto

  DOI：10.1039/p19940002993

  日期：——

  It is revealed that NH-protected 2,3,4,5-tetrahydro-1H-2-benzazepine 4 is acylated on C-8 with greater than 95% regioselectivity. This regioselectivity has been applied to the synthesis of 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one 3a, an inhibitor of acetylcholinesterase (AChE). The regioselectivities of the acylation of the following nitrogen heterocycles have also been studied: 4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepine 6, 2,3,4,5-tetrahydro-1H-2-benzazepin-3-one 7, 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one 8, 7,11b,12,13-tetrahydro-5H-isoindolo[2,1-b][2] benzazepin-7-one 9 and 6,7,9,13b-tetrahydro-5H-isoindolo[1,2-a][2]benzazepin-9-one 10. A molecular orbital (MO) calculation on the Lewis acid coordinated substrates has been used for predicting regioselectivity.