2-(2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl)-2-azaspiro[4.5]decane-1,3-dione | 83928-77-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl)-2-azaspiro[4.5]decane-1,3-dione
• 英文别名: 2-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-2-azaspiro[4.5]decane-1,3-dione
• CAS: 83928-77-2
• 化学式: C₂₂H₃₁N₃O₃
• 分子量: 385.506
• InChiKey: LSXHXXWLWSECTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  53.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  加巴喷丁杂质E 、 1-(2-aminoethyl)-4-(2-methoxyphenyl)piperazine 以 水 为溶剂， 反应 1.5h， 以70%的产率得到2-(2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl)-2-azaspiro[4.5]decane-1,3-dione
  参考文献：
  名称：

  Synthesis, anticonvulsant activity and 5-HT1A, 5-HT2A receptor affinity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 2-azaspiro[4.4]nonane and [4.5]decane-1,3-dione

  摘要：

  The synthesis, physicochemical and pharmacological properties of new N-[(4-arylpiperazin-1-yl)-alkyl]-2-azaspiro[4.4]nonane- (8a-c, 10a-d) and [4.5]decane-1,3-dione (9a-c, 11a-d) derivatives were described. The antiepileptic effects of those compounds were examined by a maximal electroshock (MES) and a pentylenetetrazole (sc. PTZ) tests, and their neurotoxicity was determined using a rota-rod test. Compounds 8c, 9c, 10c, d, 11c, d with a CF3 group at the 3-position of the 4-arylpiperazine fragment exhibited anti-seizure properties in the MES model; in contrast, their 2-CH3 and 2-OCH3 analogues were inactive in both the tests used. Moreover, since the investigated compounds belong to the class of long-chain arylpiperazines, their serotonin 5-HT1A and 5-HT2A receptor affinity was determined. The relationship between the length of alkylene spacer and 5-HT1A/5-HT2A receptor activity was observed. Compounds with an ethylene and a propylene bridge (10a-d and 11a-d) were 380-fold more potent (K-i ranged from 3.1 to 94 nM for 5-HT1A and 32-465 nM for 5-HT2A) than their methylene analogues (8a-c and 9a-c; Ki ranged from 81 to 370 nM for 5-HT1A and 126-1370 nM for 5-HT2A). The highest 5-HT1A receptor affinity was displayed by 2-OCH3 and 3-CF3 phenyl derivatives (10b, 11b: K-i = 6.8 and 5.7 nM, respectively, and 10c, 11c: Ki = 6.0 and 3.1 nM, respectively), while in the case of 5-HT2A receptor the highest affinity was observed for the 3-CF3 phenyl derivatives 10c, d, 11c, d (Ki ranged from 32 to 86 nM). (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.03.001

文献信息

• Synthesis, anticonvulsant activity and 5-HT1A, 5-HT2A receptor affinity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 2-azaspiro[4.4]nonane and [4.5]decane-1,3-dione
  作者：J. Obniska、M. Kołaczkowski、A.J. Bojarski、B. Duszyńska

  DOI：10.1016/j.ejmech.2006.03.001

  日期：2006.7

  The synthesis, physicochemical and pharmacological properties of new N-[(4-arylpiperazin-1-yl)-alkyl]-2-azaspiro[4.4]nonane- (8a-c, 10a-d) and [4.5]decane-1,3-dione (9a-c, 11a-d) derivatives were described. The antiepileptic effects of those compounds were examined by a maximal electroshock (MES) and a pentylenetetrazole (sc. PTZ) tests, and their neurotoxicity was determined using a rota-rod test. Compounds 8c, 9c, 10c, d, 11c, d with a CF3 group at the 3-position of the 4-arylpiperazine fragment exhibited anti-seizure properties in the MES model; in contrast, their 2-CH3 and 2-OCH3 analogues were inactive in both the tests used. Moreover, since the investigated compounds belong to the class of long-chain arylpiperazines, their serotonin 5-HT1A and 5-HT2A receptor affinity was determined. The relationship between the length of alkylene spacer and 5-HT1A/5-HT2A receptor activity was observed. Compounds with an ethylene and a propylene bridge (10a-d and 11a-d) were 380-fold more potent (K-i ranged from 3.1 to 94 nM for 5-HT1A and 32-465 nM for 5-HT2A) than their methylene analogues (8a-c and 9a-c; Ki ranged from 81 to 370 nM for 5-HT1A and 126-1370 nM for 5-HT2A). The highest 5-HT1A receptor affinity was displayed by 2-OCH3 and 3-CF3 phenyl derivatives (10b, 11b: K-i = 6.8 and 5.7 nM, respectively, and 10c, 11c: Ki = 6.0 and 3.1 nM, respectively), while in the case of 5-HT2A receptor the highest affinity was observed for the 3-CF3 phenyl derivatives 10c, d, 11c, d (Ki ranged from 32 to 86 nM). (c) 2006 Elsevier SAS. All rights reserved.