3-(4-氯苯基)-3-甲酰基吡咯烷-1-羧酸乙酯 | 660844-91-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 3-(4-氯苯基)-3-甲酰基吡咯烷-1-羧酸乙酯
• 英文名称: 3-(4-chlorophenyl)-3-formylpyrrolidine-1-carboxylic acid ethyl ester
• 英文别名: ethyl 3-(4-chlorophenyl)-3-formylpyrrolidine-1-carboxylate
• CAS: 660844-91-7
• 化学式: C₁₄H₁₆ClNO₃
• 分子量: 281.739
• InChiKey: MLHAQVIEDHFQCK-UHFFFAOYSA-N

物化性质

• 沸点：
  393.8±42.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.64
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-(4-氯苯基)-3-甲酰基吡咯烷-1-羧酸乙酯 在 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 、 sodium hexamethyldisilazane 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 为溶剂， 反应 23.0h， 生成 4-[3-(4-Chlorophenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-1-(4-fluorophenyl)butan-1-one
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Metabolism-Based Analogues of Haloperidol Incapable of Forming MPP+-like Species

  摘要：

  The long-term, irreversible, Parkinsonism-like side effects of haloperidol have been speculated to involve several mechanisms. More recently, it has been speculated that the metabolic transformation to MPP+-like species may contribute to the Parkinsonism-like side effects. Because BCPP+ and its reduced analogue have been shown to possess the potential to destroy dopamine receptors in the nigrostriatum, we have designed new analogues of haloperidol lacking the structural features necessary to form neurotoxic quaternary species but retaining their dopamine-binding capacity. The most potent agent at the D2 receptor, the homopiperidine analogue 11, was found to be equipotent to haloperidol. It was also of interest to identify analogues with DA binding profiles similar to that of clozapine at the dopamine receptor subtypes. Evaluation of the proposed agents shows that the ratio of D2 to D4 (2) binding of clozapine was mimicked by 7 [K-i(D2) = 33, K-i(D3) = 200, K-i(D4) = 11 nM; K-i(D2)/K-i(D4) = 3] and 9 [K-i(D2) = 44, K-i(D3) = 170, K-i(D4) = 24 nM; K-i(D2)/K-i(D4) = 2]. A preliminary in-vivo testing of compound 7 shows that its behavioral profile is similar to that of clozapine. This profile suggests that there is a need for further evaluation of these two synthetic agents and their enantiomers for efficacy and lack of catalepsy in animal models.

  DOI：

  10.1021/jm0301033
• 作为产物：
  描述：

  4-(4-氯苯基)-1,2,3,6-四氢吡啶盐酸盐 在 三氟化硼乙醚 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 乙醚 、 二氯甲烷 、 丙酮 为溶剂， 反应 23.0h， 生成 3-(4-氯苯基)-3-甲酰基吡咯烷-1-羧酸乙酯
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Metabolism-Based Analogues of Haloperidol Incapable of Forming MPP+-like Species

  摘要：

  The long-term, irreversible, Parkinsonism-like side effects of haloperidol have been speculated to involve several mechanisms. More recently, it has been speculated that the metabolic transformation to MPP+-like species may contribute to the Parkinsonism-like side effects. Because BCPP+ and its reduced analogue have been shown to possess the potential to destroy dopamine receptors in the nigrostriatum, we have designed new analogues of haloperidol lacking the structural features necessary to form neurotoxic quaternary species but retaining their dopamine-binding capacity. The most potent agent at the D2 receptor, the homopiperidine analogue 11, was found to be equipotent to haloperidol. It was also of interest to identify analogues with DA binding profiles similar to that of clozapine at the dopamine receptor subtypes. Evaluation of the proposed agents shows that the ratio of D2 to D4 (2) binding of clozapine was mimicked by 7 [K-i(D2) = 33, K-i(D3) = 200, K-i(D4) = 11 nM; K-i(D2)/K-i(D4) = 3] and 9 [K-i(D2) = 44, K-i(D3) = 170, K-i(D4) = 24 nM; K-i(D2)/K-i(D4) = 2]. A preliminary in-vivo testing of compound 7 shows that its behavioral profile is similar to that of clozapine. This profile suggests that there is a need for further evaluation of these two synthetic agents and their enantiomers for efficacy and lack of catalepsy in animal models.

  DOI：

  10.1021/jm0301033