3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-5,6,8-trihydro-7H-isoxazolo[4,5-g]-quinolin-7-one

• 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: 3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-5,6,8-trihydro-7H-isoxazolo[4,5-g]-quinolin-7-one
• 英文别名: 3-(2-(1-benzylpiperidin-4-yl)ethyl)-5,6-dihydroisoxazolo[4,5-g]quinolin-7(8H)-one；3-[2-(1-benzylpiperidin-4-yl)ethyl]-6,8-dihydro-5H-[1,2]oxazolo[4,5-g]quinolin-7-one
• 化学式: C₂₄H₂₇N₃O₂
• 分子量: 389.497
• InChiKey: UQBAAIYCOXDDQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  58.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-叔丁氧羰基-4-碘甲基哌啶 在 sodium carbonate 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 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

文献信息

• Methods of using piperidyl-benzisoxazole and benisothiazole derivatives
  申请人：Pfizer Inc.

  公开号：US05538984A1

  公开（公告）日：1996-07-23

  Disclosed 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。
• Agents and crystals for improving excretory potency of urinary bladder
  申请人：——

  公开号：US20020177593A1

  公开（公告）日：2002-11-28

  Agents for improving potentcy of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action. Particularly, crystals of a tricyclic, condensed, heterocyclic derivative are provided, which possess an excellent action to inhibit acetylcholine esterase and an action to improve the excretory potency of urinary bladder. As an example, crystals of of 8-[3-[1-[(3-fluorophenyl)-methyl]-4-piperidinyl]-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one or a salt thereof and pharmaceutical compositions containing them are disclosed.

  改善膀胱功能的药剂，包括一种非卡巴酯类胺化合物，具有乙酰胆碱酯酶抑制作用。特别地，提供了一种三环、紧凑、杂环衍生物的晶体，具有优异的抑制乙酰胆碱酯酶作用和改善膀胱排泄功能的作用。例如，揭示了8-[3-[1-[(3-氟苯基)-甲基]-4-哌啶基]-1-氧代丙基]-1,2,5,6-四氢-4H-吡咯烷[3,2,1-ij]-喹啉-4-酮或其盐和含有它们的药物组合物。
• [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。
• Heterocyclic-cyclic amine derivatives
  申请人：——

  公开号：US20020028834A1

  公开（公告）日：2002-03-07

  Compounds of the formula 1 wherein R 1 R 2 , R 7 , R 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.

  化合物的式子为1，其中R1、R2、R7、R8、X、Y、M和L的定义如下。式I的化合物是胆碱酯酶抑制剂，并可用于增强患有痴呆和阿尔茨海默病的患者的记忆力。
• Agents for improving excretory potency of urinary bladder
  申请人：——

  公开号：US20040116457A1

  公开（公告）日：2004-06-17

  Agents for improving excretory potency of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action.

  改善排泄能力的尿道代理，包括一种非卡巴酯型胺类化合物，具有乙酰胆碱酯酶抑制作用。