6,8-dihydro-3-methyl-7H-pyrrolo<2,3-g>-1,2-benzisoxazol-7-one | 145509-26-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 6,8-dihydro-3-methyl-7H-pyrrolo<2,3-g>-1,2-benzisoxazol-7-one
• 英文别名: 6,8-Dihydro-3-methyl-7H-pyrrolo[5,4-g]-1,2-benzisoxazol-7-one；3-methyl-6,8-dihydropyrrolo[2,3-g][1,2]benzoxazol-7-one
• CAS: 145509-26-8
• 化学式: C₁₀H₈N₂O₂
• 分子量: 188.186
• InChiKey: PPHXUWNGJBJVIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,8-dihydro-3-methyl-7H-pyrrolo<2,3-g>-1,2-benzisoxazol-7-one 在 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 3-(2-Piperidin-4-ylethyl)-6,8-dihydropyrrolo[2,3-g][1,2]benzoxazol-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：

  5-acetyl-1,3-dihydro-4-hydroxy-2H-indol-2-one, 5-oxime acetate 在 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以34%的产率得到6,8-dihydro-3-methyl-7H-pyrrolo<2,3-g>-1,2-benzisoxazol-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
• 作为试剂：
  描述：

  1,2-苯异唑 、 1-叔丁氧羰基-4-碘甲基哌啶 在 二异丙胺 作用下， 以 四氢呋喃 、 6,8-dihydro-3-methyl-7H-pyrrolo<2,3-g>-1,2-benzisoxazol-7-one 为溶剂， 以51%的产率得到4-<2-<7,8-dihydro-7-oxo-6H-pyrrolo<2,3-g>-1,2-benzisoxazol-3-yl>ethyl>-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester
  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

文献信息

• [EN] HETEROCYCLIC-CYCLIC AMINE DERIVATIVES
  申请人：PFIZER INC.

  公开号：WO1992017475A1

  公开（公告）日：1992-10-15

  (EN) Compounds of formula (I) wherein R1, R2, R7, R8, X, Y, M and L are defined as below. The compounds of formula (I) are cholinesterase inhibitors and are useful in enhancing memory in patients suffering from dementia and Alzheimer's disease.(FR) Composés de la formule (I) dans laquelle R1, R2, R7, R8, X, Y, M et L sont définis ci-dessous. Les composés de la formule (I) sont des inhibiteurs de la cholinestérase et ils sont utiles pour améliorer la mémoire chez des patients souffrant de démence ou de la maladie d'Alzheimer.

  (中) 公式（I）中的化合物，其中R1、R2、R7、R8、X、Y、M和L的定义如下。公式（I）中的化合物是胆碱酯酶抑制剂，对于患有痴呆症和阿尔茨海默病的患者增强记忆有用。
• Benzisoxazole and benzisothizole derivatives as cholinesterase inhibitors
  申请人：Pfizer

  公开号：US05750542A1

  公开（公告）日：1998-05-12

  Described herein are compounds of the formula ##STR1## wherein R.sup.1 R.sup.2, R.sup.7, R.sup.8, X, Y, M and L are defined as below. The compounds of formula I are cholinesterase inhibitors and are useful in enhancing memory in patients suffering from dementia and Alzheimer's disease.

  本文描述的是式子 ##STR1## 中的化合物，其中R.sup.1、R.sup.2、R.sup.7、R.sup.8、X、Y、M和L的定义如下。公式I的化合物是胆碱酯酶抑制剂，对于患有痴呆症和阿尔茨海默病的患者增强记忆力很有用。
• Heterocyclic-cyclic amine derivatives
  申请人：Eisai Co., LTD

  公开号：US06326382B1

  公开（公告）日：2001-12-04

  Compounds of the formula wherein R1 R2, R7, R8, X, Y, M and L are defined as below. The compounds of formula I are cholinesterase inhibitors and are useful in enhancing memory in patients suffering from dementia and Alzheimer's disease.

  公式为I的化合物，其中R1 R2，R7，R8，X，Y，M和L的定义如下。公式I的化合物是胆碱酯酶抑制剂，并且在增强患有痴呆和阿尔茨海默病的患者的记忆方面非常有用。
• Heterocyclic-cyclic amine derivatives as cholinesterase inhibitors
  申请人：Pfizer Inc.

  公开号：US06498255B2

  公开（公告）日：2002-12-24

  Compounds of the formula wherein R1 R2, R7, R8, X, Y, M and L are defined as below. The compounds of formula I are cholinesterase inhibitors and are useful in enhancing memory in patients suffering from. dementia and Alzheimer's disease.

  该公式的化合物中，R1，R2，R7，R8，X，Y，M和L的定义如下。公式I的化合物是胆碱酯酶抑制剂，对于患有痴呆症和阿尔茨海默病的患者增强记忆力非常有用。
• HETEROCYCLIC-CYCLIC AMINE DERIVATIVES
  申请人：PFIZER INC.

  公开号：EP0646115A1

  公开（公告）日：1995-04-05