5,6-dimethoxy-2-(N-propylamino)indan | 162751-96-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5,6-dimethoxy-2-(N-propylamino)indan
• 英文别名: 5,6-dimethoxy-N-propyl-2,3-dihydro-1H-inden-2-amine
• CAS: 162751-96-4
• 化学式: C₁₄H₂₁NO₂
• 分子量: 235.326
• InChiKey: VMLZHSSDQKGNHE-UHFFFAOYSA-N

物化性质

• 沸点：
  347.6±42.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6-dimethoxy-2-(N-propylamino)indan 在 硼烷四氢呋喃络合物 、 氰基磷酸二乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.5h， 生成 [2-(4-Bromo-phenyl)-ethyl]-(5,6-dimethoxy-indan-2-yl)-propyl-amine
  参考文献：
  名称：

  Dopamine D₃ Receptor Antagonists. 1. Synthesis and Structure−Activity Relationships of 5,6-Dimethoxy-N-alkyl- and N-Alkylaryl-Substituted 2-Aminoindans

  摘要：

  5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D-3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D-3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D-3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D-3 binding affinity, the D-2 affinity is also enhanced, resulting in a less than 4-fold preference for the D-3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D-3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3. Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (similar to 65%) from the indanone 5c.

  DOI：

  10.1021/jm010145w
• 作为产物：
  描述：

  3-(3,4-dimethoxy-phenyl)-propionyl chloride 在 10percent Pd/C 盐酸 、 lithium aluminium tetrahydride 、 三氯化铝 、 亚硝酸丁酯 、 氰基磷酸二乙酯 、 硫酸 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 20.0~40.0 ℃ 、344.75 kPa 条件下， 反应 18.5h， 生成 5,6-dimethoxy-2-(N-propylamino)indan
  参考文献：
  名称：

  Dopamine D₃ Receptor Antagonists. 1. Synthesis and Structure−Activity Relationships of 5,6-Dimethoxy-N-alkyl- and N-Alkylaryl-Substituted 2-Aminoindans

  摘要：

  5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D-3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D-3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D-3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D-3 binding affinity, the D-2 affinity is also enhanced, resulting in a less than 4-fold preference for the D-3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D-3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3. Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (similar to 65%) from the indanone 5c.

  DOI：

  10.1021/jm010145w

文献信息

• Binge behavior regulators
  申请人：Golan Ezekiel

  公开号：US10137096B2

  公开（公告）日：2018-11-27

  Methods and compositions utilizing 2-aminoindan derivatives collectively represented by Formula I as described and defined in the specification for regulating binge behavior, particularly binge drinking, are disclosed.

  本发明公开了利用说明书中描述和定义的式 I 所代表的 2-氨基茚满衍生物来调节酗酒行为，特别是酗酒的方法和组合物。
• Alcoholic beverage substitutes
  申请人：Clearmind Medicine Inc.

  公开号：US11528924B2

  公开（公告）日：2022-12-20

  Alcoholic beverage-substitutes such as a beer-substitute, a wine-substitute, a cider-substitute, an alcopop-substitute or a spirit-substitute beverage, comprising a base liquid (e.g., a base beverage) and a 2-aminoindan derivative such as defined by Formula I in the specification are disclosed.

  本发明公开了酒精饮料代用品，如啤酒代用品、葡萄酒代用品、苹果酒代用品、酒精饮料代用品或烈性酒代用品，包括基础液体（如基础饮料）和2-氨基茚满衍生物（如说明书中式I所定义）。
• 2-AMINOINDANS AS SELECTIVE DOPAMINE D3 LIGANDS
  申请人：THE UPJOHN COMPANY

  公开号：EP0712387A1

  公开（公告）日：1996-05-22
• BINGE BEHAVIOR REGULATORS
  申请人：Golan, Ezekiel

  公开号：EP3230255B1

  公开（公告）日：2020-03-18
• ALCOHOLIC BEVERAGE SUBSTITUTES
  申请人：Golan, Ezekiel

  公开号：EP3230256A1

  公开（公告）日：2017-10-18