5,6,8,9,14,14b-Hexahydro-benzindolo<2.3-a>chinolizin | 13896-23-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5,6,8,9,14,14b-Hexahydro-benzindolo<2.3-a>chinolizin
• 英文别名: 3,13-Diazapentacyclo[11.8.0.02,10.04,9.016,21]henicosa-2(10),4,6,8,16,18,20-heptaene
• CAS: 13896-23-6
• 化学式: C₁₉H₁₈N₂
• 分子量: 274.365
• InChiKey: QMFZCDNIHZUHSQ-UHFFFAOYSA-N

物化性质

• 熔点：
  167-168 °C
• 沸点：
  459.9±40.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5,6,8,9,14,14b-Hexahydro-benzindolo<2.3-a>chinolizin 在 氨 、 sodium 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 28.17h， 生成 7-methyl-14-pentyl-6,7,8,9,14,15-hexahydro-5H-indolo[3,2-f][3]benzazecine
  参考文献：
  名称：

  LE300 的 Indole-NH 上的残留调节多巴胺受体的亲和力和选择性

  摘要：

  为了进一步研究 azecine 型多巴胺受体拮抗剂类中的 SAR，我们合成了一系列衍生物，在先导化合物 LE300 的吲哚-NH 处被不同的烷基链取代，此外还有苯丙基、烯丙基、炔丙基和乙酰基残基。目标化合物对所有人类多巴胺受体 (D1-D5) 的亲和力通过放射性配体结合测定进行研究，并通过钙测定进行研究。发现多巴胺受体的亲和力和选择性都受替代物性质的影响。N14-甲基化衍生物对所有 D-受体显示出最高的亲和力。一般来说，亲和力随着 N-烷基链长的增加而降低。与我们的领先 LE300 相比，不同的取代基部分导致了亲和力和选择性的改变。

  DOI：

  10.1002/ardp.201000121
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 sodium tetrahydroborate 、 乙醇 作用下， 生成 5,6,8,9,14,14b-Hexahydro-benzindolo<2.3-a>chinolizin
  参考文献：
  名称：

  Sugasawa; Takano, Chemical and pharmaceutical bulletin, 1959, vol. 7, p. 417,425

  摘要：

  DOI：

文献信息

• Dopamine/Serotonin Receptor Ligands, Part III [1]: Synthesis and Biological Activities of 7, 7′—Alkylene-bis-6, 7, 8, 9, 14, 15-hexahydro-5H-benz[d]indolo[2, 3-g]azecines — Application of the Bivalent Ligand Approach to a Novel Type of Dopamine Receptor Antagonist
  作者：Ashraf H. Abadi、Stefan Lankow、Barbara Hoefgen、Michael Decker、Matthias U. Kassack、Jochen Lehmann

  DOI：10.1002/1521-4184(200211)335:8<367::aid-ardp367>3.0.co;2-c

  日期：2002.11

  A series of 7, 7′—alkylene‐bridged dimers(7a—e) of the benz [d]indolo[3, 2‐f]azecine derivative LE300 was synthesized. Affinity and functional activity at dopamine D1 and D2 receptors were estimated by radioligand binding and a functional Ca2+ assay. All the new bivalent ligands showed significant binding affinities to both D1 and D2 receptorswith an optimal distance between the two monomeric recognition

  合成了苯并 [d] indolo [3, 2-f] zecine 衍生物 LE300 的一系列 7, 7'-亚烷基桥连二聚体 (7a-e)。对多巴胺 D1 和 D2 受体的亲和力和功能活性通过放射性配体结合和功能性 Ca2 + 测定来估计。所有新的二价配体均显示出对 D1 和 D2 受体的显着结合亲和力，两个单体识别单元之间的最佳距离为 6 个亚甲基部分。D1/D2 选择性模式取决于间隔长度。通过测量激动剂诱导的细胞内 Ca2+ 增加的抑制作用，对于所有二价化合物没有检测到 (7a, b) 或仅检测到中等 (7c-e) 功能活性。
• 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.
• Synthesis and Biological Activity of Novel Heterocyclic Ring Systems: Imidazo[4’,5’:3,4]pyrido[2,1-a]isoquinolines and Imidazo[4,5-f][3]benzazecines
  作者：Jochen Lehmann、Robert Otto、Christoph Enzensperger

  DOI：10.3987/com-12-12574

  日期：——

  Derivatives of two novel heterocyclic ring systems were synthesized and their affinities for dopamine receptors were measured. The compounds were obtained by reacting histamine with 2-(2-bromoethyl)benzaldehyde including an atypical Pictet-Spengler condensation, which afforded basic and not the usual neutral or acidic conditions. The resulting imidazo[4',5':3,4]pyrido[2,1-a]isoquinoline derivative 4 was Boc protected at the most basic imidazole nitrogen, the isoquinoline nitrogen then quaternized by using methyl iodide and the tetracyclic isoquinolinium salt was both deprotected and cleaved under Birch conditions in one step to give a tricyclic imidazo[4,5-f][3]benzazecine derivative (3) by opening two 6-membered heterocycles towards one 10-membered. Radioligand binding studies showed a significant affinity of the moderately constrained 3 but not of 4 for dopamine receptors. Similar to the analogous indolo-benzazecine LE300, a preference of 3 for the D-1 receptor family was observed, but with some loss of affinity over all.
• Lehmann Jochen, Nieger Martin, Witt Thomas, Heterocycles, 41 (1995) N 1, S 119-130
  作者：Lehmann Jochen, Nieger Martin, Witt Thomas

  DOI：——

  日期：——
• Indoles XIII. Syntheses and Stereochemistry of 14H-Bisindolo[2,3-a][3,2-h]quinolizine and of Some Benz[a]indolo[3,2-h]quinolizines
  作者：Jochen Lehmann、Martin Nieger、Thomas Witt

  DOI：10.3987/com-94-6915

  日期：——

  Starting from hexahydrobenz[a]indolo[3,2-h]quinolizine (1a-c) and hexahydrobisindolo[2,3-a][3,2-h]quinolizine (4)(2) we succeeded in generating their completely dehydrogenated derivatives. The structures were investigated by H-1- and C-13-nmr spectroscopy as well as by X-ray analysis.