Ethoxycarbonyl 4-(4-chlorophenyl)-4-oxobutanoate | 1026985-43-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Ethoxycarbonyl 4-(4-chlorophenyl)-4-oxobutanoate
• CAS: 1026985-43-2
• 化学式: C₁₃H₁₃ClO₅
• 分子量: 284.696
• InChiKey: HAKONGBKTPKXRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethoxycarbonyl 4-(4-chlorophenyl)-4-oxobutanoate 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 66.0h， 生成 N-[4-(4-fluorophenyl)-4-oxobutyl]-N-4-(4'-chlorophenyl)-4-triisopropylsilyloxybutylamine
  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：

  3-(4-氯苯甲酰)丙酸 、 氯甲酸乙酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 Ethoxycarbonyl 4-(4-chlorophenyl)-4-oxobutanoate
  参考文献：
  名称：

  新型“疏肠”线粒体DBI受体复合物（mDRC）配体的化学性质，结合亲和力和行为特性。

  摘要：

  线粒体DBI受体复合物（mDRC；以前称为外围苯二氮卓受体）与神经甾体（如硫酸孕烯醇酮，硫酸脱氢表雄酮等）的产生有关。为了获得有关mDRC在大脑中的功能的更多信息，我们已经在体内和体外构建和测试了一系列新型的配体2-芳基吲哚-3-乙酰胺。本文详述的SAR研究描述了高亲和力与mDRC结合所需的一些结构特征。在大多数情况下，新的配体是通过Fischer吲哚合成法制备的。探讨了酰胺氮上烷基长度和数目的变化，以及在一个或两个芳环上的卤素取代基的影响。还合成了一些用于研究的配体，它们代表了母体结构的构象受限形式。广泛的筛选研究表明，这些吲哚乙酰胺对mDRC具有高度选择性，因为它们无法以任何显着的亲和力与其他受体系统结合。通过[3H] 4'-氯二氮杂苯的置换测量，发现一些配体对mDRC表现出低纳摩尔范围的Ki值。还显示了这些配体的一个子集可刺激C6-2B胶质瘤细胞线粒体中孕烯醇酮的形成，其EC50约为3

  DOI：

  10.1021/jm00072a010

文献信息

• Chemistry, binding affinities, and behavioral properties of a new class of "antineophobic" mitochondrial DBI receptor complex (mDRC) ligands
  作者：A. P. Kozikowski、D. Ma、James Brewer、S. Sun、E. Costa、E. Romeo、A. Guidotti

  DOI：10.1021/jm00072a010

  日期：1993.10

  detailed herein delineate some of the structural features required for high affinity binding to the mDRCs. In most cases the new ligands were prepared by use of the Fischer indole synthesis. Variations in the length and number of the alkyl groups on the amide nitrogen were probed together with the effects of halogen substituents on one or both of the aryl rings. Some ligands were also synthesized for

  线粒体DBI受体复合物（mDRC；以前称为外围苯二氮卓受体）与神经甾体（如硫酸孕烯醇酮，硫酸脱氢表雄酮等）的产生有关。为了获得有关mDRC在大脑中的功能的更多信息，我们已经在体内和体外构建和测试了一系列新型的配体2-芳基吲哚-3-乙酰胺。本文详述的SAR研究描述了高亲和力与mDRC结合所需的一些结构特征。在大多数情况下，新的配体是通过Fischer吲哚合成法制备的。探讨了酰胺氮上烷基长度和数目的变化，以及在一个或两个芳环上的卤素取代基的影响。还合成了一些用于研究的配体，它们代表了母体结构的构象受限形式。广泛的筛选研究表明，这些吲哚乙酰胺对mDRC具有高度选择性，因为它们无法以任何显着的亲和力与其他受体系统结合。通过[3H] 4'-氯二氮杂苯的置换测量，发现一些配体对mDRC表现出低纳摩尔范围的Ki值。还显示了这些配体的一个子集可刺激C6-2B胶质瘤细胞线粒体中孕烯醇酮的形成，其EC50约为3
• 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.