6,7,8,9,10,11-hexahydroazepino[2,1-b]quinazoline-12(6H)-thione | 881890-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6,7,8,9,10,11-hexahydroazepino[2,1-b]quinazoline-12(6H)-thione
• 英文别名: 8,9,10,11-tetrahydro-6H-azocino[2,1-b]quinazoline-13(7H)-thione；6,7,8,9,10,11-Hexahydroazocino[2,1-b]quinazoline-13-thione
• CAS: 881890-07-9
• 化学式: C₁₄H₁₆N₂S
• 分子量: 244.36
• InChiKey: RCKYSUJKWSRQPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  47.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6,7,8,9,10,11-hexahydroazepino[2,1-b]quinazoline-12(6H)-thione 、 1,7-二氨基庚烷 在 silver nitrate 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以79%的产率得到N,N'-bis[6,7,8,9,10,11-hexahydro-13H-azocino[2,1-b]quinazolin-13-ylidene]heptane-1,7-diamine
  参考文献：
  名称：

  Homobivalent Quinazolinimines as Novel Nanomolar Inhibitors of Cholinesterases with Dirigible Selectivity toward Butyrylcholinesterase

  摘要：

  Homobivalent dimers of quinazolinimines, which bridge the imine nitrogen atoms via a hepta-and an octamethylene spacer, with different ring sizes of the alicycles were synthesized from the corresponding quinazolinethiones. The resulting compounds show > 100-fold increase of inhibitory activities compared to related monomeric compounds yielding low-nanomolar inhibitors. For heptamethylene dimers, mixed inhibition profiles were obtained, whereas for the octamethylene compounds selectivity toward butyrylcholinesterase (> 180) can be achieved with an eight-membered alicycle.

  DOI：

  10.1021/jm060682m
• 作为产物：
  描述：

  邻氨基苯甲酸 在 劳森试剂 、 triethyloxonium fluoroborate 作用下， 生成 6,7,8,9,10,11-hexahydroazepino[2,1-b]quinazoline-12(6H)-thione
  参考文献：
  名称：

  Probing the mid-gorge of cholinesterases with spacer-modified bivalent quinazolinimines leads to highly potent and selective butyrylcholinesterase inhibitors

  摘要：

  The spacer structure of homobivalent quinazolinimes acting as potent acetyl-(AChE)- and butyrylcholinesterase (BChE) inhibitors was chemically modified introducing tertiary amine and acyl-amide moieties, and the activities at both ChEs were evaluated. Molecular docking was applied to explain the data and probe the capacity of the mid-gorge site of both ChEs. The novel spacer structures considerably alter the biological profile of bivalent quinazolinimines with regard to both inhibitory activity and selectivity. Mutual interaction of binding to the various sites of the enzymes was further investigated by applying also different spacer lengths and ring sizes of the alicycle of the tricyclic quinazolinimines. In order to achieve selectivity toward BChE and to improve inhibitory activities, the spacer structure was optimized and identified a highly potent and selective BChE inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.034

文献信息

• Novel tricyclic quinazolinimines and related tetracyclic nitrogen bridgehead compounds as cholinesterase inhibitors with selectivity towards butyrylcholinesterase
  作者：Michael Decker、Fabian Krauth、Jochen Lehmann

  DOI：10.1016/j.bmc.2005.10.044

  日期：2006.3

  Tetracyclic nitrogen bridgehead compounds, dibenzodiazecines and tricyclic quinazolinimines, in which the size of the alicyclic ring system and the length of the alkyl chain between the quinazolinimine moiety and a phenyl ring connected to the imine nitrogen atom were changed systematically, were synthesized and their ability to inhibit acetyl- and butyrylcholinesterase (AChE/BChE), respectively, was

  合成了四环氮桥头化合物，二苯并二氮杂胺和三环喹唑啉亚胺，其中脂环环系统的大小以及喹唑啉亚胺部分和与亚胺氮原子相连的苯环之间的烷基链的长度被系统地改变，并且它们具有分别评估了乙酰胆碱酯酶和丁酰胆碱酯酶（AChE / BChE）的抑制作用。与加兰他敏和卡巴拉汀相比，已鉴定出中度和强效BChE抑制剂，它们对混合BChE表现出混合的亲和力或中度或高度选择性。
• Design, synthesis and pharmacological evaluation of hybrid molecules out of quinazolinimines and lipoic acid lead to highly potent and selective butyrylcholinesterase inhibitors with antioxidant properties
  作者：Michael Decker、Birgit Kraus、Jörg Heilmann

  DOI：10.1016/j.bmc.2008.02.083

  日期：2008.4

  A set of hybrid molecules were synthesized out of lipoic acid, alpha,omega-diamines of different lengths serving as spacers, and cholinesterase (ChE) inhibiting [2,1-b]quinazolinimines. Depending on the length of the alkylene spacer the amide hybrids are inhibitors of acetylcholinesterase (AChE) with inhibitory activities of 0.5-4.6 mu M and inhibitors of butyrylcholinesterase (BChE) with activities down to 5.7 nM, therefore greatly exceeding the inhibitory activities of the parent quinazolinimines by factors of up to 1000. Due to increasing activity at BChE with increasing length of the alkylene spacer similar to 100-fold selectivity toward BChE is reached with a hepta- and an octamethylene spacer. Kinetic measurements reveal competitive and reversible inhibition of both ChEs by the hybrids. Furthermore, cell viability and antioxidant activity (using the ORAC-fluorescein assay) of several hybrids were evaluated, showing cytotoxicity at concentrations from 3.7 to 10.2 mu M and antioxidant properties are in the range of 0.4-0.8 Trolox equivalents (lipoic acid = 0.6). (C) 2008 Elsevier Ltd. All rights reserved.