tert-butyl (2-dimethylaminoethyl)-{4-methyl-6-[(E)-3-(4-trifluoromethoxyphenyl)acryloylamino]quinolin-2-yl}carbamate | 865536-53-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: tert-butyl (2-dimethylaminoethyl)-{4-methyl-6-[(E)-3-(4-trifluoromethoxyphenyl)acryloylamino]quinolin-2-yl}carbamate
• CAS: 865536-53-4
• 化学式: C₂₉H₃₃F₃N₄O₄
• 分子量: 558.601
• InChiKey: ZGBWALUDZKIIIM-NTEUORMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  84.0
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-dimethylaminoethyl)-{4-methyl-6-[(E)-3-(4-trifluoromethoxyphenyl)acryloylamino]quinolin-2-yl}carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以70%的产率得到(E)-N-[2-(2-Dimethylamino-ethylamino)-4-methyl-quinolin-6-yl]-3-(4-trifluoromethoxy-phenyl)-acrylamide
  参考文献：
  名称：

  6-Acylamino-2-aminoquinolines as Potent Melanin-Concentrating Hormone 1 Receptor Antagonists. Identification, Structure−Activity Relationship, and Investigation of Binding Mode

  摘要：

  Novel 6-acylamino-2-aminoquinoline melanin-concentrating hormone 1 receptor (MCHIR) antagonists were identified by sequential in silico screening with 3D pharmacophore models derived from a series of benzamide antagonists. The structure- activity relationship exploration by synthesis of analogues found structural demands around the western part of the compounds to be quite specific, whereas much structural freedom was found in the eastern part. Vvhile these compounds in general suffered from poor solubility properties, the 4-trifluoromethoxy-phenoxyacetamide western appendage provided a favorable combination of activity and solubility properties. The amine in the eastern appendage, originally required by the pharmacophore model and believed to interact with Asp123 in transmembrane 3 of MCH1R, could be removed without diminishing affinity or functional activity of the compounds. Docking studies suggested that the Asp123 interacts preferentially with the nitrogen of the central quinoline. Synthesis and testing of specific analogues supported our revised binding mode hypothesis.

  DOI：

  10.1021/jm050103y
• 作为产物：
  描述：

  4-甲基-2-氯-喹啉 在 palladium on activated charcoal 氢气 、 硝酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 100.0 ℃ 、101.33 kPa 条件下， 反应 44.0h， 生成 tert-butyl (2-dimethylaminoethyl)-{4-methyl-6-[(E)-3-(4-trifluoromethoxyphenyl)acryloylamino]quinolin-2-yl}carbamate
  参考文献：
  名称：

  6-Acylamino-2-aminoquinolines as Potent Melanin-Concentrating Hormone 1 Receptor Antagonists. Identification, Structure−Activity Relationship, and Investigation of Binding Mode

  摘要：

  Novel 6-acylamino-2-aminoquinoline melanin-concentrating hormone 1 receptor (MCHIR) antagonists were identified by sequential in silico screening with 3D pharmacophore models derived from a series of benzamide antagonists. The structure- activity relationship exploration by synthesis of analogues found structural demands around the western part of the compounds to be quite specific, whereas much structural freedom was found in the eastern part. Vvhile these compounds in general suffered from poor solubility properties, the 4-trifluoromethoxy-phenoxyacetamide western appendage provided a favorable combination of activity and solubility properties. The amine in the eastern appendage, originally required by the pharmacophore model and believed to interact with Asp123 in transmembrane 3 of MCH1R, could be removed without diminishing affinity or functional activity of the compounds. Docking studies suggested that the Asp123 interacts preferentially with the nitrogen of the central quinoline. Synthesis and testing of specific analogues supported our revised binding mode hypothesis.

  DOI：

  10.1021/jm050103y