1H-2-苯并吡喃-5,6-二醇,1-(氨基甲基)-3,4-二氢-3-三环[3.3.1.13,7]癸-1-基-,盐酸,(1S-顺)-(9CI) | 147060-66-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 1H-2-苯并吡喃-5,6-二醇,1-(氨基甲基)-3,4-二氢-3-三环[3.3.1.13,7]癸-1-基-,盐酸,(1S-顺)-(9CI)
• 英文名称: (1S,3R)-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride
• 英文别名: (1S,3R)-3-Adamantan-1-yl-1-aminomethyl-isochroman-5,6-diol; hydrochloride
• CAS: 147060-66-0；134456-62-5
• 化学式: C₂₀H₂₇NO₃*ClH
• 分子量: 365.9
• InChiKey: BWHPNJVKFAPVOG-LDXFOSHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.68
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  75.71
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  2-(1-金刚烷)环氧乙烷 在 盐酸 、 lithium aluminium tetrahydride 、 正丁基锂 、 叠氮化锂 、 三氟化硼乙醚 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 1H-2-苯并吡喃-5,6-二醇,1-(氨基甲基)-3,4-二氢-3-三环[3.3.1.13,7]癸-1-基-,盐酸,(1S-顺)-(9CI)
  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

文献信息

• The enantioselective synthesis of the potent dopamine D1 agonist (1R,3S)-3-(1'-adamantyl)-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyran (A77636)
  作者：Michael P. DeNinno、Richard J. Perner、Howard E. Morton、Stanley DiDomenico

  DOI：10.1021/jo00052a025

  日期：1992.12

  The synthesis of both enantiomers of the title compound is described. The corresponding racemic compound (+/-)-1 was previously shown to be a highly potent and selective dopamine Dl agonist. Key to the synthesis of the enantiomers was the oxazaborolidine-catalyzed asymmetric reduction of the alpha-bromomethyl ketone 12 which led to the optically enriched epoxide 7. An aryllithium addition to the epoxide followed by a diastereospecific cyclization to the isochroman system furnished compound 17, which was deprotected to afford (-)-1 with >99.5% optical purity.