3-bromo-4-(4-chlorophenyl)-N,N-dihexyl-4-oxobutanamide | 247085-34-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-bromo-4-(4-chlorophenyl)-N,N-dihexyl-4-oxobutanamide
• CAS: 247085-34-3
• 化学式: C₂₂H₃₃BrClNO₂
• 分子量: 458.867
• InChiKey: XERAZMTYPJYEDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  27
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氨基-3,5二氯吡啶 、 3-bromo-4-(4-chlorophenyl)-N,N-dihexyl-4-oxobutanamide 以 N,N-二甲基甲酰胺 为溶剂， 以15%的产率得到2-[6,8-Dichloro-2-(4-chloro-phenyl)-imidazo[1,2-a]pyridin-3-yl]-N,N-dihexyl-acetamide
  参考文献：
  名称：

  Structure−Activity Relationships and Effects on Neuroactive Steroid Synthesis in a Series of 2-Phenylimidazo[1,2-a]pyridineacetamide Peripheral Benzodiazepine Receptors Ligands

  摘要：

  A series of 36 imidazopyridineacetamides (2-37) were designed and synthesized to evaluate the effects of structural changes on the amide nitrogen at both central (CBRs) and peripheral benzodiazepine receptors (PBRs). These changes include variations in the length and number of the alkyl groups as well as introduction of different aromatic, heteroaromatic, and conformationally constrained groups. The affinities of these compounds for CBRs and PBRs were determined, and the results indicate that bulkiness of the substituents, their branching, and length beyond an optimal value may cause hindrance to the ligand in its interaction with the receptor. The presence of aromatic or conformationally constrained substituents on the carboxamide nitrogen can be conducive to high affinity and selectivity. Furthermore, the ability of a subset of the most active ligands to stimulate synthesis of neuroactive steroids in plasma and brain was evaluated in vivo and in vitro. Compound 3 exhibited very marked effects on the peripheral and central synthesis of neuroactive steroids, while 36 (potent at subnanomolar level) showed a slight ability to affect neuroactive steroid content in the cerebral cortex.

  DOI：

  10.1021/jm049610q
• 作为产物：
  描述：

  3-(4-氯苯甲酰)丙酸 在 溴 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 生成 3-bromo-4-(4-chlorophenyl)-N,N-dihexyl-4-oxobutanamide
  参考文献：
  名称：

  Structure−Activity Relationships and Effects on Neuroactive Steroid Synthesis in a Series of 2-Phenylimidazo[1,2-a]pyridineacetamide Peripheral Benzodiazepine Receptors Ligands

  摘要：

  A series of 36 imidazopyridineacetamides (2-37) were designed and synthesized to evaluate the effects of structural changes on the amide nitrogen at both central (CBRs) and peripheral benzodiazepine receptors (PBRs). These changes include variations in the length and number of the alkyl groups as well as introduction of different aromatic, heteroaromatic, and conformationally constrained groups. The affinities of these compounds for CBRs and PBRs were determined, and the results indicate that bulkiness of the substituents, their branching, and length beyond an optimal value may cause hindrance to the ligand in its interaction with the receptor. The presence of aromatic or conformationally constrained substituents on the carboxamide nitrogen can be conducive to high affinity and selectivity. Furthermore, the ability of a subset of the most active ligands to stimulate synthesis of neuroactive steroids in plasma and brain was evaluated in vivo and in vitro. Compound 3 exhibited very marked effects on the peripheral and central synthesis of neuroactive steroids, while 36 (potent at subnanomolar level) showed a slight ability to affect neuroactive steroid content in the cerebral cortex.

  DOI：

  10.1021/jm049610q

文献信息

• Novel 2-Phenylimidazo[1,2-<i>a</i>]pyridine Derivatives as Potent and Selective Ligands for Peripheral Benzodiazepine Receptors:  Synthesis, Binding Affinity, and in Vivo Studies
  作者：Giuseppe Trapani、Massimo Franco、Andrea Latrofa、Laura Ricciardi,、Angelo Carotti、Mariangela Serra、Enrico Sanna、Giovanni Biggio、Gaetano Liso

  DOI：10.1021/jm991035g

  日期：1999.9.1

  (PBR) benzodiazepine receptors. The structure-activity relationship studies detailed herein indicate the key structural features required for high affinity and selectivity for PBR. Substitution on the imidazopyridine nucleus at position 8 with lipophilic substituents and the presence of one chlorine atom at the para position of the phenyl ring at C(2) are crucial features for high binding affinity and

  在两个中心位置（CBR）评估了一系列2-苯基咪唑并[1,2-a]吡啶乙酰胺在位置6和8（化合物17-31）以及酰胺氮（化合物32-40）上的取代基作用和外围（PBR）苯二氮卓受体。本文详细描述的结构-活性关系研究表明，高亲和力和选择性对PBR具有关键的结构特征。在位置8的咪唑并吡啶核上具有亲脂性取代基，并且在C（2）的苯环对位上存在一个氯原子，这对于高结合亲和力和对PBR的选择性至关重要。一小部分活性配体（即17，20，26，34，和35）在表达了克隆的人GABA（A）受体的非洲爪蟾卵母细胞中对CBR的作用进行了体外评估，并在体内评估了刺激类固醇如孕烯醇酮，孕酮，异戊四烯酮和异四氢脱氧皮质类固醇（THDOC）合成的能力。与化合物35不同，化合物17、20、26和34显着增加了血浆和大脑皮层中神经活性类固醇的水平。
• Structure−Activity Relationships and Effects on Neuroactive Steroid Synthesis in a Series of 2-Phenylimidazo[1,2-<i>a</i>]pyridineacetamide Peripheral Benzodiazepine Receptors Ligands
  作者：Giuseppe Trapani、Valentino Laquintana、Nunzio Denora、Adriana Trapani、Angela Lopedota、Andrea Latrofa、Massimo Franco、Mariangela Serra、Maria Giuseppina Pisu、Ivan Floris、Enrico Sanna、Giovanni Biggio、Gaetano Liso

  DOI：10.1021/jm049610q

  日期：2005.1.1

  A series of 36 imidazopyridineacetamides (2-37) were designed and synthesized to evaluate the effects of structural changes on the amide nitrogen at both central (CBRs) and peripheral benzodiazepine receptors (PBRs). These changes include variations in the length and number of the alkyl groups as well as introduction of different aromatic, heteroaromatic, and conformationally constrained groups. The affinities of these compounds for CBRs and PBRs were determined, and the results indicate that bulkiness of the substituents, their branching, and length beyond an optimal value may cause hindrance to the ligand in its interaction with the receptor. The presence of aromatic or conformationally constrained substituents on the carboxamide nitrogen can be conducive to high affinity and selectivity. Furthermore, the ability of a subset of the most active ligands to stimulate synthesis of neuroactive steroids in plasma and brain was evaluated in vivo and in vitro. Compound 3 exhibited very marked effects on the peripheral and central synthesis of neuroactive steroids, while 36 (potent at subnanomolar level) showed a slight ability to affect neuroactive steroid content in the cerebral cortex.