2,3-Dimethoxy-5,6,8,9-tetrahydro-13bH-dibenzochinolizin | 30562-57-3

• 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: 2,3-Dimethoxy-5,6,8,9-tetrahydro-13bH-dibenzochinolizin
• 英文别名: 2,3-dimethoxy-5,6,8,9-tetrahydro-dibenzo quinolizine；2,3-dimethoxy-5,6,8,9-tetrahydro-13bH-dibenzo[a,h]quinolizine；2,3-dimethoxydibenzoquinolizidine；5,6,8,9-Tetrahydro-2,3-dimethoxy-13bH-dibenzoquinolizine；2,3-Dimethoxy-5,8,9,13b-tetrahydro-6H-dibenzochinolizin；2,3-Dimethoxy-5,6,8,9-tetrahydro-dibenzochinolizin；2,3-Dimethoxy-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline；2,3-dimethoxy-6,8,9,13b-tetrahydro-5H-isoquinolino[1,2-a]isoquinoline
• CAS: 30562-57-3
• 化学式: C₁₉H₂₁NO₂
• 分子量: 295.381
• InChiKey: ZAAPJIIHGVAKOE-UHFFFAOYSA-N

物化性质

• 熔点：
  128 °C
• 沸点：
  419.6±45.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-Dimethoxy-5,6,8,9-tetrahydro-13bH-dibenzochinolizin 在 氢溴酸 作用下， 反应 4.0h， 以46%的产率得到2,3-dihydroxy-5,6,8,9-tetrahydro-13bH-dibenzoquinolizine
  参考文献：
  名称：

  Synthesis and Molecular Modeling of 1-Phenyl-1,2,3,4-tetrahydroisoquinolines and Related 5,6,8,9-Tetrahydro-13bH-dibenzo[a,h]quinolizines as D1 Dopamine Antagonists

  摘要：

  New 1-phenyl-1,2,3,4-tetrahydroisoquinolines and related 5,6,8,9-tetrahydro-13bH-dibenzo[a,h]-quinolizines were prepared as ring-contracted analogs of the prototypical 1-phenyl-2,3,4,5-tetrahydrobenzazepines (e.g., SCH23390) as a continuation of our studies to characterize the antagonist binding pharmacophore of the D-1 dopamine receptor. Receptor affinity was assessed by competition for [H-3]SCH23390 binding sites in rat striatal membranes. The 6-bromo-1-phenyltetrahydroisoquinoline analog 2 of SCH23390 1 had D-1 binding affinity similar to that for the previously reported 6-chloro analog 6, whereas the 6,7-dihydroxy analog 5 had significantly lower D-1 affinity. Conversely, neither 6-monohydroxy- (3) nor 7-monohydroxy-1-phenyltetrahydroisoquinolines (4) had significant affinity for the D-1 receptor. These results demonstrate that 6-halo and 7-hydroxy substituents influence D-1 binding affinity of the 1-phenyltetrahydroisoquinolines in a fashion similar to their effects on 1-phenyltetrahydrobenzazepines. azepines. The conformationally constrained 3-chloro-2-hydroxytetrahydrodibenzoquinolizine 9 had much lower affinity relative to the corresponding, and more flexible, 6-chloro-7-hydroxy-1-phenyltetrahydroisoquinoline 6. Similarly, 2,3-dihydroxytetrahydrodibenzoquinolizine 10 had much lower D-1 affinity compared to dihydrexidine 14, a structurally similar hexahydrobenzo[a]phenanthridine that is a high-affinity full D-1 agonist. Together, these data not only confirm the effects of the halo and hydroxy substitutents on the parent nucleus but demonstrate the pharmacophoric importance of both the nitrogen position and the orientation of the accessory phenyl ring in modulating D-1 receptor affinity and function. Molecular modeling studies and conformational analyses were conducted using the data from these new analogs in combination with the data from compounds previously synthesized. The resulting geometries were used to refine a working model of the D-1 antagonist pharmacophore using conventional quantitative structure-activity relationships and three-dimensional QSAR (CoMFA).

  DOI：

  10.1021/jm00051a008
• 作为产物：
  描述：

  6,7-二甲氧基-3,4-二氢异喹啉 在 盐酸 、 lithium aluminium tetrahydride 、 PPA 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 13.75h， 生成 2,3-Dimethoxy-5,6,8,9-tetrahydro-13bH-dibenzochinolizin
  参考文献：
  名称：

  分子内α-酰胺-烷基化反应在合成二苯并/a,h/喹啉中的应用

  摘要：

  摘要 5,6,9-Trihydro-8H-dibenzo [a,h] quinolizin-8-ones 6 由 3,4-二氢异-喹啉 1 和苯乙酰氯通过分子内 α-酰胺烷基化反应的加合物获得。

  DOI：

  10.1080/00397919108016425

文献信息

• Cyclisierungen von N-(2-Phenylethyl)-2-(2-hydroxyethyl)-benzamiden
  作者：Hans-Jürgen Mika、Werner Meise

  DOI：10.1002/ardp.19853180212

  日期：——

  Die Cyclisierung der Hydroxyamide 3 unter Bischler‐Napieralski‐Bedingungen erfolgt in Abhängigkeit von der Substitution der Aromaten auf drei verschiedene Reaktionsweisen: Während die im Phenylethylamin‐Teil (Ring A) nicht aktivierten Amide 3c und 3d nur den Ring C schließen, entsteht bei dem in A aktivierten, jedoch in Ring D (Lacton‐Teil) für einen nucleophilen Angriff desaktivierten Amid 3b anschließend

  羟基酰胺 3 在 Bischler-Napieralski 条件下的环化以三种不同的方式发生，具体取决于芳族化合物的取代：而在苯乙胺部分（环 A）中未活化的酰胺 3c 和 3d 仅闭合环 C，在 A 中激活，但在环 D（内酯部分）中酰胺 3b 因亲核攻击而失活，然后是环 B；相反，在仅在 A 中激活的 3a 中，首先发生 Bischler-Napieralski 反应（环 B），然后发生分子内 N-烷基化（环 C）。
• 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
  作者：Barbara Hoefgen、Michael Decker、Patrick Mohr、Astrid M. Schramm、Sherif A. F. Rostom、Hussein El-Subbagh、Peter M. Schweikert、Dirk R. Rudolf、Matthias U. Kassack、Jochen Lehmann

  DOI：10.1021/jm050846j

  日期：2006.1.1

  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.
• 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：——
• VLAEMINCK F.; COCK E. DE; TOURWE D.; BINST G. VAN, HETEROCYCLES, 1981, 15, NO 2, SPEC. ISSUE, 1213-1218
  作者：VLAEMINCK F.、 COCK E. DE、 TOURWE D.、 BINST G. VAN

  DOI：——

  日期：——
• MIKA, H. -J.;MEISE, W., ARCH. PHARM., 1985, 318, N 2, 168-174
  作者：MIKA, H. -J.、MEISE, W.

  DOI：——

  日期：——