6-chloro-2,3-dihydropyrrolo[2,1-b]quinazoline-9(1H)-thione | 911366-48-8

• 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-chloro-2,3-dihydropyrrolo[2,1-b]quinazoline-9(1H)-thione
• 英文别名: 6-chloro-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-thione；6-chloro-2,3-dihydro-1H-pyrrolo[2,1-b]quinazoline-9-thione
• CAS: 911366-48-8
• 化学式: C₁₁H₉ClN₂S
• 分子量: 236.725
• InChiKey: QPAOPGCFRSUWHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 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-chloro-2,3-dihydropyrrolo[2,1-b]quinazoline-9(1H)-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49%的产率得到N,N'-bis[6-chloro-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-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：

  6-chloro-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以89%的产率得到6-chloro-2,3-dihydropyrrolo[2,1-b]quinazoline-9(1H)-thione
  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

文献信息

• 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.