5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline | 77929-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline
• 英文别名: dibenzoquinolizidine；dibenzo[a,h]quinolizine；5,6,8,9-Tetrahydro-13bh-dibenzo[a,h]quinolizine；6,8,9,13b-tetrahydro-5H-isoquinolino[1,2-a]isoquinoline
• CAS: 77929-54-5
• 化学式: C₁₇H₁₇N
• 分子量: 235.329
• InChiKey: DVMYNVGOZADPIR-UHFFFAOYSA-N

物化性质

• 熔点：
  76 °C
• 沸点：
  359.0±11.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline 在 盐酸 、 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 27.0h， 生成 13b-hydroxy-7-methyl-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolinium chloride
  参考文献：
  名称：

  Synthesis and Reactivity of Dibenz[d,g]azecin-14(5H)-ones

  摘要：

  DOI：

  10.3987/com-06-10681
• 作为产物：
  描述：

  2-(1-苯基-3,4-二氢-1H-异喹啉-2-基)-乙醇 在 PPA 作用下， 反应 6.0h， 以68%的产率得到5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline
  参考文献：
  名称：

  Dopamine/Serotonin Receptor Ligands. 10: SAR Studies on Azecine-type Dopamine Receptor Ligands by Functional Screening at Human Cloned D₁, D_2L, and D₅ Receptors with a Microplate Reader Based Calcium Assay Lead to a Novel Potent D₁/D₅ Selective Antagonist

  摘要：

  On the basis of the benz[d]indolo[2,3-g]azecine derivative I (LE300), structure-activity relations were investigated in order to identify the pharmacophore in this new class of ligands. Various structural modifications were performed and the inhibitory activities at human cloned D-1, D-2L, and D-5 receptors were measured by using a simple fluorescence microplate reader based calcium assay. Subsequently, the affinities of active compounds were estimated by radioligand binding experiments. Deleting one of the aromatic rings as well as replacing it by a phenyl moiety abolishes the inhibitory activities almost completely. Contraction of the 10-membered central ring decreases them significantly. The replacement of indole by thiophene or N-methylpyrrole reduces the inhibitory activity, whereas replacing the indole by benzene increases it. Finally, the hydroxylated dibenz[d,g]azecine derivative 11d (LE404) was found to be more active than the lead I in the functional calcium assay as well as in radioligand displacement experiments.

  DOI：

  10.1021/jm050846j

文献信息

• Fishing for Accessory Binding Sites at GPCRs with ‘Loop-Hooks’ - An Approach towards Selectivity? Part I
  作者：Thomas Tröger、Maximilian Langenberg、Sicheng Zhong、Dario Ambrosini、Christoph Enzensperger

  DOI：10.1002/cbdv.201300292

  日期：2014.2

  Receptor-subtype selectivity is an important issue in medicinal chemistry and can become very difficult to achieve if the actual binding pockets of the respective receptors are highly conserved. For such cases, known unselective ligands could be equipped with a spacer that sticks outside the actual orthosteric binding pocket towards the extracellular loops. The end of the spacer bears certain functional

  受体亚型的选择性是药物化学中的一个重要问题，如果高度保守各个受体的实际结合口袋，则很难实现。对于这样的情况，已知的非选择性配体可以配备有间隔物，该间隔物在实际的正构结合口袋之外朝向细胞外环粘附。间隔基的末端带有某些官能团，以使得能够与结合腔外的受体残基进行​​特异性或非特异性的相互作用。我们的实验表明，通过这种“环钩”可以在多巴胺D1家族内实现选择性。
• Pharmaceutical dopamine glycoconjugate compositions and methods of their preparation and use
  申请人：christian T. Samuel

  公开号：US20050250739A1

  公开（公告）日：2005-11-10

  Hydrophilic transportable N-linked glycosyl dopaminergic prodrug compounds according to FORMULA V and methods of their use, wherein, Ring 1 comprises an aryl or heteroaryl ring having 4 to 8 carbon atoms, among which atoms are counted “X” and “Y”; each of X and Y is optional; X, when present is either —C(R 1 ) 2 — or —C(R 1 ) 2 —; Y, when present, is either —CH 2 — or —CH 2 —CH 2 —; z, R 5 and R 5′ . are optional, and when present z, R 5 and R 5′ together form a lower alkyl or a substituted lower alkyl moiety; N is part of either an amine or an amide linkage; E is a saccharide which forms a linkage with N through a single bond from a carbon or oxygen atom thereof; R 1 and R 4 are selected form the group consisting of hydrogen, hydroxyl, halogen, halo-lower alkyl, alkoxyl, alkoxyl-lower alkyl, halo-alkoxy, thioamido, amidosulfonyl, alkoxylcarbonyl, carboxamide, aminocarbonyl, and alkylamino-carbonyl; R 2 and R 3 are hydroxyl; R 5 and R 6 , when present, are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carbonyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialkylamino-carbonyl; and, R 6 and R 6′ are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carboxyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialylamino-carbonyl, with the proviso that Ring 1 is capable of binding to any of: a dopaminergic receptor selected from the group consisting of a D1 receptor and a D5 receptor; a DAT transporter; a VMAT transporter; and, with the proviso that E is capable of binding to a GLUT transporter selected from the group consisting of a GLUT1 receptor and a GLUT3 receptor.

  根据FORMULA V，水亲性可运输的N-连接糖基的多巴胺前药化合物及其使用方法，其中，环1包括一个芳基或杂环芳基环，其中含有4至8个碳原子，其中原子被计为“X”和“Y”；X和Y各自是可选的；当存在X时，它是- C（R1）2-或-C（R1）2-；当存在Y时，它是-CH2-或-CH2-CH2-；z，R5和R5'是可选的，当存在z，R5和R5'时，它们共同形成较低的烷基或取代较低的烷基基团；N是氨基或酰胺连接的一部分；E是一个糖类，通过其碳或氧原子之一的单键与N形成连接；R1和R4从选组中选择，包括氢，羟基，卤素，卤代较低烷基，烷氧基，烷氧基较低烷基，卤代烷氧基，硫酰胺基，氨基磺酰基，烷氧羰基，羧酰胺，氨基羰基和烷基氨基羰基；R2和R3是羟基；当存在时，R5和R6从选组中选择，包括氢，羟基，烷氧基，羰基，烷氧基羰基，氨基羰基，烷基氨基羰基和二烷基氨基羰基；而R6和R6'从选组中选择，包括氢，羟基，烷氧基，羧基，烷氧基羰基，氨基羰基，烷基氨基羰基和二烷基氨基羰基，但前提是环1能够与以下任何一个结合：从选组中选择的多巴胺能感受器，包括D1受体和D5受体；DAT转运体；VMAT转运体；前提是E能够与以下从选组中选择的GLUT转运体结合：GLUT1受体和GLUT3受体。
• PHARMACEUTICAL DOPAMINE GLYCOCONJUGATE COMPOSITIONS AND METHODS OF THEIR PREPARATION AND USE
  申请人：Christian Samuel T.

  公开号：US20080194802A1

  公开（公告）日：2008-08-14

  Hydrophilic transportable N-linked glycosyl dopaminergic prodrug compounds according to FORMULA V and methods of their use, wherein, Ring 1 comprises an aryl or heteroaryl ring having 4 to 8 carbon atoms, among which atoms are counted “X” and “Y”; each of X and Y is optional; X, when present is either —C(R 1 ) 2 — or —C(R) 2 —; Y, when present, is either —CH 2 — or —CH 2 —CH 2 —; z, R 5 and R 5′ are optional, and when present z, R 5 and R 5′ together form a lower alkyl or a substituted lower alkyl moiety; N is part of either an amine or an amide linkage; E is a saccharide which forms a linkage with N through a single bond from a carbon or oxygen atom thereof; R 1 and R 4 are selected form the group consisting of hydrogen, hydroxyl, halogen, halo-lower alkyl, alkoxyl, alkoxyl-lower alkyl, halo-alkoxy, thioamido, amidosulfonyl, alkoxylcarbonyl, carboxamide, aminocarbonyl, and alkylamino-carbonyl; R 2 and R 3 are hydroxyl; R 5 and R 6 , when present, are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carbonyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialkylamino-carbonyl; and, R 6 and R 6′ are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carboxyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialylamino-carbonyl, with the proviso that Ring 1 is capable of binding to any of: a dopaminergic receptor selected from the group consisting of a D1 receptor and a D5 receptor; a DAT transporter; a VMAT transporter; and, with the proviso that E is capable of binding to a GLUT transporter selected from the group consisting of a GLUT1 receptor and a GLUT3 receptor.

  根据公式V及其使用方法，水亲和性可转运的N-连接糖基多巴胺前药化合物，其中，环1包括4至8个碳原子的芳基或杂芳基环，其中原子计算为“X”和“Y”；X和Y各自是可选的；当存在X时，它是—C（R1）2—或—C（R）2—；当存在Y时，它是—CH2—或—CH2—CH2—；z，R5和R5'是可选的，当存在时，z，R5和R5'共同形成较低的烷基或取代较低的烷基基团；N是胺或酰胺连接的一部分；E是一种糖，通过其碳或氧原子中的单键与N形成连接；R1和R4从氢、羟基、卤素、卤素较低烷基、烷氧基、烷氧基较低烷基、卤素烷氧基、硫酰胺、氨基磺酰、烷氧基羰基、羧酰胺、氨基羰基和烷基氨基羰基中选择；R2和R3是羟基；当存在R5和R6时，它们从氢、羟基、烷氧基、羰基、烷氧基羰基、氨基羰基、烷基氨基羰基和二烷基氨基羰基中选择；R6和R6'从氢、羟基、烷氧基、羧基、烷氧基羰基、氨基羰基、烷基氨基羰基和二烷基氨基羰基中选择，但环1能够与以下任意一种结合：D1受体和D5受体中选择的多巴胺能受体；DAT转运体；VMAT转运体；并且，E能够与GLUT1受体和GLUT3受体中选择的GLUT转运体结合。
• Treatment of anhedonia
  申请人：Nathanson L. Donald

  公开号：US20060217394A1

  公开（公告）日：2006-09-28

  A therapeutic method for the enhancement of mood in patients afflicted with iatrogenic anhedonia secondary to chronic increases in the availability and/or efficiency of serotonin, with or without increases in the availability and/or efficiency of norepinephrine.

  一种治疗方法，用于改善因长期增加血清素的供应量和/或效率，同时或不增加去甲肾上腺素的供应量和/或效率而继发的先天性失神症患者的情绪。
• Vlaeminck, F.; Cock, E. De; Tourwe, D., Heterocycles, 1981, vol. 15, # 2, p. 1213 - 1218
  作者：Vlaeminck, F.、Cock, E. De、Tourwe, D.、Binst, G. Van

  DOI：——

  日期：——