N-苄基-2-氯-N,3-二甲基喹啉-4-甲酰胺 | 1027193-73-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: N-苄基-2-氯-N,3-二甲基喹啉-4-甲酰胺
• 英文名称: N-benzyl-2-chloro-N,3-dimethylquinoline-4-carboxamide
• CAS: 1027193-73-2
• 化学式: C₁₉H₁₇ClN₂O
• 分子量: 324.81
• InChiKey: XBLOUTZUOXAUPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-苄基-2-氯-N,3-二甲基喹啉-4-甲酰胺 、 异氰基乙酸叔丁酯 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以46%的产率得到tert-butyl 5-[benzyl(methyl)carbamoyl]-4-methylimidazo[1,5-a]quinoline-3-carboxylate
  参考文献：
  名称：

  咪唑并[1,5- a ]喹啉作为中央苯二氮杂Re受体高强度配体的设计，合成及生物学评价

  摘要：

  设计并合成了一系列咪唑并[1,5- a ]喹啉衍生物作为中心苯并二氮杂pine受体（CBR）配体。大多数化合物在亚微摩尔和亚纳摩尔范围内都具有很高的CBR亲和力和K i值，并在其结构亲和力关系中进行了有趣的调节。特别是，氟衍生物7w（K i = 0.44 nM）导致了迄今为止所述的咪唑并[1,5- a ]喹啉衍生物中最有效的配体。总体而言，这些观察结果证实了以下假设：在与咪唑[1,5-]的位置4和5相互作用的CBR结合位点区域中存在一个明显饱和的亲脂性大袋。一个]喹啉核。体内生物学特性表明，化合物7a，c，d，l，m，q，r，w显示出抗焦虑和抗记忆删除活性，而没有经典的1,4-BDZ的令人讨厌的肌松反应副作用。此外，7l，q，r和8i降低大鼠脑切片中缺血样条件引起的乳酸脱氢酶（LDH）释放的作用表明这些咪唑并[1,5- a ]喹啉衍生物具有神经保护作用。

  DOI：

  10.1021/acs.jmedchem.6b00034
• 作为产物：
  描述：

  2-羟基-3-甲基-4-喹啉羧酸 在 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 N-苄基-2-氯-N,3-二甲基喹啉-4-甲酰胺
  参考文献：
  名称：

  Further Studies on the Interaction of the 5-Hydroxytryptamine₃ (5-HT₃) Receptor with Arylpiperazine Ligands. Development of a New 5-HT₃ Receptor Ligand Showing Potent Acetylcholinesterase Inhibitory Properties

  摘要：

  Novel arylpiperazine derivatives bearing lipophilic probes were designed, synthesized, and evaluated for their potential ability to interact with the 5-hydroxytryptamine(3) (5-HT3) receptor. Most of the new compounds show subnanomolar 5-HT3 receptor affinity. Ester 6bc showing a picomolar K-i value is one of the most potent 5-HT3 receptor ligands so far synthesized. The structure-affinity relationship study suggests the existence of a certain degree of conformational freedom of the amino acid residues interacting with the substituents in positions 3 and 4 of the quipazine quinoline nucleus. Thus, the tacrine-related heterobivalent ligand 6o was designed in an attempt to capitalize on the evidence of such a steric tolerance. Compound 6o shows a nanomolar potency for both the 5-HT3 receptor and the human AChE and represents the first example of a rationally designed high-affinity 5-HT3 receptor ligand showing nanomolar AChE inhibitory activity. Finally, the computational analysis performed on compound 6o allowed the rationalization of the structure-energy determinants for AChE versus BuChE selectivity and revealed the existence of a subsite at the boundary of the 5-HT3 receptor extracellular domain, which could represent a "peripheral" site similar to that evidenced in the AChE gorge.

  DOI：

  10.1021/jm0493461

文献信息

• Further Studies on the Interaction of the 5-Hydroxytryptamine₃ (5-HT₃) Receptor with Arylpiperazine Ligands. Development of a New 5-HT₃ Receptor Ligand Showing Potent Acetylcholinesterase Inhibitory Properties
  作者：Andrea Cappelli、Andrea Gallelli、Monica Manini、Maurizio Anzini、Laura Mennuni、Francesco Makovec、M. Cristina Menziani、Stefano Alcaro、Francesco Ortuso、Salvatore Vomero

  DOI：10.1021/jm0493461

  日期：2005.5.1

  Novel arylpiperazine derivatives bearing lipophilic probes were designed, synthesized, and evaluated for their potential ability to interact with the 5-hydroxytryptamine(3) (5-HT3) receptor. Most of the new compounds show subnanomolar 5-HT3 receptor affinity. Ester 6bc showing a picomolar K-i value is one of the most potent 5-HT3 receptor ligands so far synthesized. The structure-affinity relationship study suggests the existence of a certain degree of conformational freedom of the amino acid residues interacting with the substituents in positions 3 and 4 of the quipazine quinoline nucleus. Thus, the tacrine-related heterobivalent ligand 6o was designed in an attempt to capitalize on the evidence of such a steric tolerance. Compound 6o shows a nanomolar potency for both the 5-HT3 receptor and the human AChE and represents the first example of a rationally designed high-affinity 5-HT3 receptor ligand showing nanomolar AChE inhibitory activity. Finally, the computational analysis performed on compound 6o allowed the rationalization of the structure-energy determinants for AChE versus BuChE selectivity and revealed the existence of a subsite at the boundary of the 5-HT3 receptor extracellular domain, which could represent a "peripheral" site similar to that evidenced in the AChE gorge.
• Design, Synthesis, and Biological Evaluation of Imidazo[1,5-<i>a</i>]quinoline as Highly Potent Ligands of Central Benzodiazepine Receptors
  作者：Andrea Cappelli、Maurizio Anzini、Federica Castriconi、Giorgio Grisci、Marco Paolino、Carlo Braile、Salvatore Valenti、Germano Giuliani、Salvatore Vomero、Angela Di Capua、Laura Betti、Gino Giannaccini、Antonio Lucacchini、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Maria Frosini、Lorenzo Ricci、Gianluca Giorgi、Maria Paola Mascia、Giovanni Biggio

  DOI：10.1021/acs.jmedchem.6b00034

  日期：2016.4.14

  nucleus. The in vivo biological characterization revealed that compounds 7a,c,d,l,m,q,r,w show anxiolytic and antiamnestic activities without the unpleasant myorelaxant side effects of the classical 1,4-BDZ. Furthermore, the effect of 7l,q,r, and 8i in lowering lactate dehydrogenase (LDH) release induced by ischemia-like conditions in rat brain slices suggested neuroprotective properties for these imidazo[1

  设计并合成了一系列咪唑并[1,5- a ]喹啉衍生物作为中心苯并二氮杂pine受体（CBR）配体。大多数化合物在亚微摩尔和亚纳摩尔范围内都具有很高的CBR亲和力和K i值，并在其结构亲和力关系中进行了有趣的调节。特别是，氟衍生物7w（K i = 0.44 nM）导致了迄今为止所述的咪唑并[1,5- a ]喹啉衍生物中最有效的配体。总体而言，这些观察结果证实了以下假设：在与咪唑[1,5-]的位置4和5相互作用的CBR结合位点区域中存在一个明显饱和的亲脂性大袋。一个]喹啉核。体内生物学特性表明，化合物7a，c，d，l，m，q，r，w显示出抗焦虑和抗记忆删除活性，而没有经典的1,4-BDZ的令人讨厌的肌松反应副作用。此外，7l，q，r和8i降低大鼠脑切片中缺血样条件引起的乳酸脱氢酶（LDH）释放的作用表明这些咪唑并[1,5- a ]喹啉衍生物具有神经保护作用。