4-[3-(4-Chlorophenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-1-(4-fluorophenyl)butan-1-one | 52423-71-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[3-(4-Chlorophenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-1-(4-fluorophenyl)butan-1-one
• CAS: 52423-71-9
• 化学式: C₂₂H₂₅ClFNO₂
• 分子量: 389.897
• InChiKey: YEHRQVUHEWQQQF-UHFFFAOYSA-N

物化性质

• 沸点：
  536.6±50.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(4-氯苯基)-1,2,3,6-四氢吡啶-1-羧酸乙酯 在 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 、 三氟化硼乙醚 、 sodium hexamethyldisilazane 、 potassium carbonate 、 间氯过氧苯甲酸 、 potassium iodide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 46.0h， 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

文献信息

• Design, Synthesis, and Evaluation of Metabolism-Based Analogues of Haloperidol Incapable of Forming MPP+-like Species
  作者：M. Lyles-Eggleston、R. Altundas、J. Xia、D. M. N. Sikazwe、P. Fan、Q. Yang、S. Li、W. Zhang、X. Zhu、A. W. Schmidt、M. Vanase-Frawley、A. Shrihkande、A. Villalobos、R. F. Borne、S. Y. Ablordeppey

  DOI：10.1021/jm0301033

  日期：2004.1.1

  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.