1,2,3,4,5,6-六氢苯并[B]氮杂环辛四烯 | 7124-93-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1,2,3,4,5,6-六氢苯并[B]氮杂环辛四烯
• 英文名称: 1,2,3,4,5,6-hexahydrobenzo[b]azocine
• 英文别名: 1,2,3,4,5,6-hexahydro-1-benzazocine
• CAS: 7124-93-8
• 化学式: C₁₁H₁₅N
• mdl: MFCD12755898
• 分子量: 161.247
• InChiKey: VTIJFGNTDHLPLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  1,2,3,4,5,6-六氢苯并[B]氮杂环辛四烯 在 lithium aluminium tetrahydride 、 硫酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 3,4,5,6-tetrahydrobenzo[b]azocin-1(2 H)-amine
  参考文献：
  名称：

  Development of high-affinity 5-HT3 receptor antagonists. Structure-affinity relationships of novel 1,7-annulated indole derivatives. 1

  摘要：

  On the basis of the structures of ondansetron and GR 65,630, its ring-opened C-linked methylimidazole analogue, novel 1,7-annelated indole derivatives were synthesized as potential 5-HT3 antagonists. Receptor binding studies show that all compounds display a high affinity for the 5-HT3 receptors. In both series annelation results in compounds being 7 and 4 times more potent than the references ondansetron and GR 65,630, respectively. Similar to ondansetron, the 1,7-annelated indoles show little stereoselectivity. The (-)-isomers are only slightly more potent than the (+)-isomers. The receptor binding profile of l-10-[(2-methyl-1H-imidazol-1-yl)methyl]-5,6,8,9,10,11-hexahydro-4H-pyrido[3,2,1-jk]carbazol-11-one hydrochloride (24b) (INN cilansetron) shows that the compound displays, besides a high affinity for 5-HT3 receptors (K(i) = 0. 19 nM), a weak affinity for sigma-receptors (K(i) = 340 nM), muscarine M1 receptors (K(i) = 910 nM), and 5-HT4 receptors (K(i_ = 960 nM) and no affinity (K(i) greater-than-or-equal-to 5000 nM) for all the other receptor types tested (n = 37). The new compounds fit the proposed necessary chemical template for binding: a heteroaromatic ring system, a coplanar carbonyl group, and a nitrogen center at well-defined distances. The enhanced potency of the annelated 1,7-indole derivatives indicates that the extra ring provides a favorable hydrophobic area for interaction with the 5-HT3 receptor site. In vivo cilansetron is more potent and induces less central side effects than ondansetron. At present cilansetron is in clinical trials.

  DOI：

  10.1021/jm00075a026
• 作为产物：
  描述：

  benzosuberone oxime 在 dichloroaluminum hydride 作用下， 以 环戊基甲醚 为溶剂， 以69%的产率得到1,2,3,4,5,6-六氢苯并[B]氮杂环辛四烯
  参考文献：
  名称：

  肟与铝还原剂的扩环反应。

  摘要：

  研究了杂环酮肟和碳环酮肟与几种还原剂如 AlHCl2、AlH3（铝烷）、LiAlH4、LiAlH(OtBu)3 和 (MeOCH2CH2O)2AlH2Na（Red-Al）的扩环反应。在还原剂中，环戊基甲基醚 (CPME) 中的 AlHCl2 (LiAlH4:AlCl3 = 1:3) 已被发现是适合该反应的试剂，并且重排的环状仲胺以良好到极好的收率获得。

  DOI：

  10.3390/molecules17067348

文献信息

• 4-heterocyclyl-substituted quinazoline derivatives, processes for their
  申请人：Pfizer Inc.

  公开号：US05736534A1

  公开（公告）日：1998-04-07

  This invention relates to certain 4-aminoquinazolines and the pharmaceutically acceptable salts and stereoisomers thereof, the formula whereof are described herein. The compounds are useful for the treatment of hyperproliferative diseases, particularly as anti-cancer agents.

  这项发明涉及某些4-氨基喹唑啉及其药用可接受的盐和立体异构体，其公式在本文件中有所描述。这些化合物用于治疗过度增殖性疾病，特别是作为抗癌剂。
• [EN] DIACYLGLYCEROL KINASE MODULATING COMPOUNDS<br/>[FR] COMPOSÉS MODULANT LA DIACYLGLYCÉROL KINASE
  申请人：CARNA BIOSCIENCES INC

  公开号：WO2021130638A1

  公开（公告）日：2021-07-01

  The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.

  本公开提供了调节二酰基甘油激酶的化合物以及用于治疗癌症（包括实体瘤）和病毒感染（如HIV或乙型肝炎病毒感染）的药物组合物。这些化合物可以单独使用或与其他药物联合使用。
• [EN] BRIDGED TRICYCLIC CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE<br/>[FR] COMPOSÉS DE CARBAMOYLPYRIDONE TRICYCLIQUE PONTÉS ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：GILEAD SCIENCES INC

  公开号：WO2020197991A1

  公开（公告）日：2020-10-01

  Compounds for use in treating or preventing human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, R2, L, W1, W2, X, Y, and Z are as defined herein. Methods associated with the preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  本发明揭示了用于治疗或预防人类免疫缺陷病毒（HIV）感染的化合物。这些化合物具有以下式（I）：包括立体异构体和其药用可接受的盐，其中R1、R2、L、W1、W2、X、Y和Z如本文所定义。本发明还揭示了与这些化合物的制备和使用相关的方法，以及包含这些化合物的药物组合物。
• Collective Synthesis of Phenanthridinone through C–H Activation Involving a Pd-Catalyzed Aryne Multicomponent Reaction
  作者：Minghao Feng、Bingqing Tang、Hong-Xi Xu、Xuefeng Jiang

  DOI：10.1021/acs.orglett.6b02109

  日期：2016.9.2

  A palladium-catalyzed multicomponent reaction (MCR) involving aryne, CO, and aniline is established for straightforward assembly of a phenanthridinone scaffold through C–H bond activation. Free combination with multiple kinds of readily available anilines and arynes is facilely achieved for phenanthridinone construction without prefunctionalization. Representative natural products were subsequently

  建立了涉及芳烃，一氧化碳和苯胺的钯催化多组分反应（MCR），可通过CH键活化直接组装菲咯啶酮支架。无需预先官能化即可轻松实现与菲啶酮构建体的多种现有苯胺和芳烃的自由结合。随后，通过该MCR策略高效地合成了代表性的天然产物。对照实验和间隔NMR跟踪揭示了这一机理，尤其是CuF 2在确定该转化中前体的芳烃释放速率中的关键作用。
• Regioselective Synthesis of Heterocycles Containing Nitrogen Neighboring an Aromatic Ring by Reductive Ring Expansion Using Diisobutylaluminum Hydride and Studies on the Reaction Mechanism
  作者：Hidetsura Cho、Yusuke Iwama、Kenji Sugimoto、Seiji Mori、Hidetoshi Tokuyama

  DOI：10.1021/jo902177p

  日期：2010.2.5

  including indoline, 1,2,3,4,5,6-hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b][1,4]oxazine, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6-hexahydroazepino[3,2-b]indole, 2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H-benzothieno[3,2-b]azepine, 5,6-dihydrophenanthridine, and 5,6,11,12-tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the rearrangement was

  描述了与二异丁基氢化铝（DIBALH）稠合到芳环上的环状酮肟的还原扩环反应的系统研究。该反应区域选择性地提供了多种五至八元双环杂环或三环杂环，其包含与芳香环相邻的氮，包括二氢吲哚，1,2,3,4,5,6-六氢苯并[ b ]偶氮辛，3,4-二氢-2 H-苯并[ b ] [1,4]恶嗪，2,3,4,5-四氢苯并[ b ] [1,4]噻氮平，1,2,3,4,5,6-六氢氮庚啶[3 ，2- b ]吲哚，2,3,4,5-四氢-1 H-苯并噻吩并[2,3- b ]氮杂，2,3,4,5-四氢-1 H-苯并噻吩并[3,2- b]氮杂，5,6-二氢菲啶和5,6,11,12-四氢二苯并[ b，f ]偶氮星。基于受限的Becke三参数加Lee-Yang-Parr（B3LYP）密度泛函理论（DFT）和6-31G（d）基础集，研究了导致重排的反应机理。发现该反应通过逐步机理通过三中心过渡态进行，因为沿着本征反应坐标

表征谱图