4-<2-<5,6,7,8-tetrahydro-7-oxoisoxazolo<4,5-g>quinolin-3-yl>ethyl>-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester | 145509-23-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-<2-<5,6,7,8-tetrahydro-7-oxoisoxazolo<4,5-g>quinolin-3-yl>ethyl>-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester
• 英文别名: 4-[2-[5,6,8-Trihydro-7H-isoxazolo[4,5-g]quinolin-7-one-3-yl]ethyl]-1-piperidinecarboxylic acid, 1-(1,1-dimethylethyl)ester；tert-butyl 4-[2-(7-oxo-6,8-dihydro-5H-[1,2]oxazolo[4,5-g]quinolin-3-yl)ethyl]piperidine-1-carboxylate
• CAS: 145509-23-5
• 化学式: C₂₂H₂₉N₃O₄
• 分子量: 399.49
• InChiKey: ZXJJQKPVNONJCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  84.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-<2-<5,6,7,8-tetrahydro-7-oxoisoxazolo<4,5-g>quinolin-3-yl>ethyl>-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester 在 sodium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-5,6,8-trihydro-7H-isoxazolo[4,5-g]-quinolin-7-one
  参考文献：
  名称：

  5,7-Dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one: A Potent and Centrally-Selective Inhibitor of Acetylcholinesterase

  摘要：

  A series of N-benzylpiperidines (2a-d, 10) with novel isoxazole-containing tricycles has been prepared. This series has shown potent in vitro inhibition of the enzyme acetylcholinesterase (AChE), with IC(50)s = 0.33-3.6 nM. Compound 2a was the most potent inhibitor with an IC50 = 0.33 +/- 0.09 nM. Derivatives 2a-d and 10 displayed weak in vitro inhibition of butyrylcholinesterase (BuChE) with IC(50)s = 600-23 000 nM. The most selective compound was 2a with a BuChE/AChE ratio in excess of 4 orders of magnitude (>10 000). Pyrrolobenzisoxazole 2a also displayed a favorable profile in vivo. In microdialysis experiments, 2a produced a 200% increase in extracellular levels of acetylcholine (ACh) at a dose of 0.4 mg/kg in freely moving, conscious rats. Peripheral side effects (salivation ED(50) = 26 +/- 1.5 mg/kg) and acute lethality (LD(50)[1 h] = 42 mg/kg) were observed at >60-fold higher doses. These data indicate that 2a is an AChE inhibitor with good central selectivity and a favorable margin of safety. Compound 2a, designated as CP-118,954, is currently in clinical development for the treatment of cognitive disorders.

  DOI：

  10.1021/jm00015a002
• 作为产物：
  描述：

  6-acetyl-3,4-dihydro-7-hydroxy-2H-quinolin-2-one, 6-oxime acetate 在 吡啶 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-<2-<5,6,7,8-tetrahydro-7-oxoisoxazolo<4,5-g>quinolin-3-yl>ethyl>-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester
  参考文献：
  名称：

  5,7-Dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one: A Potent and Centrally-Selective Inhibitor of Acetylcholinesterase

  摘要：

  A series of N-benzylpiperidines (2a-d, 10) with novel isoxazole-containing tricycles has been prepared. This series has shown potent in vitro inhibition of the enzyme acetylcholinesterase (AChE), with IC(50)s = 0.33-3.6 nM. Compound 2a was the most potent inhibitor with an IC50 = 0.33 +/- 0.09 nM. Derivatives 2a-d and 10 displayed weak in vitro inhibition of butyrylcholinesterase (BuChE) with IC(50)s = 600-23 000 nM. The most selective compound was 2a with a BuChE/AChE ratio in excess of 4 orders of magnitude (>10 000). Pyrrolobenzisoxazole 2a also displayed a favorable profile in vivo. In microdialysis experiments, 2a produced a 200% increase in extracellular levels of acetylcholine (ACh) at a dose of 0.4 mg/kg in freely moving, conscious rats. Peripheral side effects (salivation ED(50) = 26 +/- 1.5 mg/kg) and acute lethality (LD(50)[1 h] = 42 mg/kg) were observed at >60-fold higher doses. These data indicate that 2a is an AChE inhibitor with good central selectivity and a favorable margin of safety. Compound 2a, designated as CP-118,954, is currently in clinical development for the treatment of cognitive disorders.

  DOI：

  10.1021/jm00015a002
• 作为试剂：
  描述：

  哌啶 、 溴甲苯 、 sodium carbonate 在 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 4-<2-<5,6,7,8-tetrahydro-7-oxoisoxazolo<4,5-g>quinolin-3-yl>ethyl>-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester 为溶剂， 以43%的产率得到3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-5,6,8-trihydro-7H-isoxazolo[4,5-g]-quinolin-7-one
  参考文献：
  名称：

  Methods of using piperidyl-benzisoxazole and benisothiazole derivatives

  摘要：

  本文披露了以下式的化合物##STR1##其中R.sup.1、R.sup.2、R.sup.7、R.sup.8、X、Y、M和L的定义如下。式I的化合物是胆碱酯酶抑制剂，对于增强患有痴呆症和阿尔茨海默病的患者的记忆有用。

  公开号：

  US05538984A1