(+/-)-1-(azidomethyl)-3-cyclohexyl-5,6-(cyclohexylidenedioxy)-3,4-dihydro-1H-2-benzopyran | 134456-11-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡喃类
• 英文名称: (+/-)-1-(azidomethyl)-3-cyclohexyl-5,6-(cyclohexylidenedioxy)-3,4-dihydro-1H-2-benzopyran
• CAS: 134456-11-4
• 化学式: C₂₂H₂₉N₃O₃
• 分子量: 383.491
• InChiKey: OWUDBGBGTURAMO-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.99
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  76.45
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (+/-)-1-(azidomethyl)-3-cyclohexyl-5,6-(cyclohexylidenedioxy)-3,4-dihydro-1H-2-benzopyran 在 盐酸 、 lithium aluminium tetrahydride 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 cis-1-(aminomethyl)-3-cyclohexyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride
  参考文献：
  名称：

  Synthesis and dopaminergic activity of 3-substituted 1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyrans: characterization of an auxiliary binding region in the D1 receptor

  摘要：

  The synthesis and dopaminergic activity of a series of C3 and nitrogen-substituted 1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyrans (isochromans) is described. The synthesis of the compounds was stereospecific for the 1,3 cis isomer, and the enantioselective synthesis of both enantiomers of one of the analogoues (20) was achieved. It was determined that all of the dopaminergic activity resides in the [1R,3S] isomer. Generally, substitution at the C3 position provided compounds with very high potency (< 10 nm EC50) and selectivity for the D1 receptor, with a wide range of intrinsic activities (60-160%). Analogues containing C3 substituents including aryl, arylalkyl, and cyclic and acyclic alkyl groups showed a marked enhancement of dopaminergic activity compared to the unsubstituted compound. As a class, the drugs were orally active in the rat rotation model with a very long duration of action.

  DOI：

  10.1021/jm00112a034
• 作为产物：
  描述：

  环己酮缩邻苯二酚 在 正丁基锂 、 叠氮化锂 、 三氟化硼乙醚 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 (+/-)-1-(azidomethyl)-3-cyclohexyl-5,6-(cyclohexylidenedioxy)-3,4-dihydro-1H-2-benzopyran
  参考文献：
  名称：

  Synthesis and dopaminergic activity of 3-substituted 1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyrans: characterization of an auxiliary binding region in the D1 receptor

  摘要：

  The synthesis and dopaminergic activity of a series of C3 and nitrogen-substituted 1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyrans (isochromans) is described. The synthesis of the compounds was stereospecific for the 1,3 cis isomer, and the enantioselective synthesis of both enantiomers of one of the analogoues (20) was achieved. It was determined that all of the dopaminergic activity resides in the [1R,3S] isomer. Generally, substitution at the C3 position provided compounds with very high potency (< 10 nm EC50) and selectivity for the D1 receptor, with a wide range of intrinsic activities (60-160%). Analogues containing C3 substituents including aryl, arylalkyl, and cyclic and acyclic alkyl groups showed a marked enhancement of dopaminergic activity compared to the unsubstituted compound. As a class, the drugs were orally active in the rat rotation model with a very long duration of action.

  DOI：

  10.1021/jm00112a034