3-amino-6,7-dimethoxy-2H-chromen-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-amino-6,7-dimethoxy-2H-chromen-2-one
• 英文别名: 3-amino-6,7-dimethoxychromen-2-one
• 化学式: C₁₁H₁₁NO₄
• 分子量: 221.213
• InChiKey: KXLCYRHMPWHEAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-6,7-dimethoxy-2H-chromen-2-one 在 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 四(三苯基膦)钯 、 chlorocyclopentadienylbis(triphenylphosphine)ruthenium(II) 、 sodium tetrakis[3,5-bis-(trifluoromethyl)phenyl]borate dihydrate 、 ammonium acetate 、 sodium hydride 、 三乙胺 、 二异丙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 氯苯 、 乙腈 、 mineral oil 为溶剂， 反应 6.58h， 生成 1-(3,4-dimethoxyphenyl)-3-[2-(3,4-dimethoxyphenyl)ethyl]-7,8-dimethoxy-4-oxo-3H-[1]benzopyrano[3,4-b]pyrrole-4-one
  参考文献：
  名称：

  钌催化的1,2-碳迁移-环异构化反应合成内酯稠合的吡咯。

  摘要：

  通过1，2-碳迁移，开发了钌催化的3-氨基-4-炔基-2 H-铬原子-2-酮的环异构化反应。合成了各种1-芳基色[3,4- b ]吡咯-4（3 H）-，收率良好。该反应用于海洋天然产物宁格林B和Lamellarin H的正式全合成。还实现了γ-丁内酯融合的吡咯衍生物的有效合成。

  DOI：

  10.1039/c9ob02363a
• 作为产物：
  描述：

  6,7-dimethoxy-3-nitrocoumarin 在 盐酸 、 tin(ll) chloride 作用下， 生成 3-amino-6,7-dimethoxy-2H-chromen-2-one
  参考文献：
  名称：

  Jackson, Yvette A., Heterocycles, 1995, vol. 41, # 9, p. 1979 - 1986

  摘要：

  DOI：

文献信息

• Synthesis of 3-aminocoumarin-<i>N</i>-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase
  作者：Nisachon Khunnawutmanotham、Cherdchai Laongthipparos、Patchreenart Saparpakorn、Nitirat Chimnoi、Supanna Techasakul

  DOI：10.3762/bjoc.14.231

  日期：——

  N-benzylpyridinium moiety through an amide-bond linkage was synthesized and evaluated for their acetylcholinesterase inhibitory activity. A number of the benzylpyridinium derivatives exhibited potent activities with inhibitory concentration (IC50) values in the nanomolar concentration range. Among them, the 2,3-difluorobenzylpyridinium-containing compound was the most potent inhibitor with an IC50 value

  合成了一系列通过酰胺键与N-苄基吡啶部分共轭的3-氨基-6,7-二甲氧基香豆素，并评估了其对乙酰胆碱酯酶的抑制活性。许多苄基吡啶鎓衍生物在纳摩尔浓度范围内均表现出有效的抑制浓度（IC50）值。其中，含2,3-二氟苄基吡啶鎓的化合物是最有效的抑制剂，IC50值为1.53±0.01 nM。对接研究表明，合成的化合物通过双重结合位点机制抑制目标酶，香豆素部分与外围阴离子位点结合，而N-苄基吡啶鎓残基与酶的催化阴离子位点结合。
• Chiral Separation, X-ray Structure, and Biological Evaluation of a Potent and Reversible Dual Binding Site AChE Inhibitor
  作者：Marco Catto、Leonardo Pisani、Eugenio de la Mora、Benny Danilo Belviso、Giuseppe Felice Mangiatordi、Andrea Pinto、Annalisa De Palma、Nunzio Denora、Rocco Caliandro、Jacques-Philippe Colletier、Israel Silman、Orazio Nicolotti、Cosimo Damiano Altomare

  DOI：10.1021/acsmedchemlett.9b00656

  日期：2020.5.14

  Acetylcholinesterase (AChE) inhibitors (AChEIs) still remain the leading therapeutic options for the symptomatic treatment of cognitive deficits associated with mild-to-moderate Alzheimer's disease. The search for new AChEIs benefits from well-established knowledge of the molecular interactions of selective AChEIs, such as donepezil and related dual binding site inhibitors. Starting from a previously

  乙酰胆碱酯酶（AChE）抑制剂（AChEIs）仍然是对症治疗与轻度至中度阿尔茨海默氏病相关的认知缺陷的主要治疗选择。对新的AChEI的搜索得益于对选择性AChEI的分子相互作用的深入了解，例如多奈哌齐和相关的双重结合位点抑制剂。从先前公开的基于香豆素的抑制剂（±）-cis-1（在纳摩尔范围内对AChE具有消旋体的活性）开始，我们通过（i）通过HPLC实现对映体1的手性拆分和（ii ）制备两个紧密的1的非手性类似物，即化合物4和6。对于顺式-1的（-）对映异构体，观察到的解毒比例高达20。（-）-顺式1 eutomer（编码为MC1420）和T之间的复合物的X射线晶体结构。加利福尼亚州AChE的测定值为2.8，对接计算结果表明，（1R，3S）绝对构型的Eutomer在能量上应比（1S，3R）构型的Eutomer更有力地结合酶。与（±）-cis-1相比，非手性类似物4和6在抑制AChE方面效果
• Design, synthesis and biological evaluation of coumarin alkylamines as potent and selective dual binding site inhibitors of acetylcholinesterase
  作者：Marco Catto、Leonardo Pisani、Francesco Leonetti、Orazio Nicolotti、Paolo Pesce、Angela Stefanachi、Saverio Cellamare、Angelo Carotti

  DOI：10.1016/j.bmc.2012.10.045

  日期：2013.1

  Acetylcholinesterase inhibitors (AChEIs) are currently the drugs of choice, although only symptomatic and palliative, for the treatment of Alzheimer's disease (AD). Donepezil is one of most used AChEIs in AD therapy, acting as a dual binding site, reversible inhibitor of AChE with high selectivity over butyrylcholinesterase (BChE). Through a combined target-and ligand-based approach, a series of coumarin alkylamines matching the structural determinants of donepezil were designed and prepared. 6,7-Dimethoxycoumarin derivatives carrying a protonatable benzylamino group, linked to position 3 by suitable linkers, exhibited fairly good AChE inhibitory activity and a high selectivity over BChE. The inhibitory potency was strongly influenced by the length and shape of the spacer and by the methoxy substituents on the coumarin scaffold. The inhibition mechanism, assessed for the most active compound 13 (IC50 7.6 nM) resulted in a mixed-type, thus confirming its binding at both the catalytic and peripheral binding sites of AChE. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis of lactone-fused pyrroles by ruthenium-catalyzed 1,2-carbon migration-cycloisomerization
  作者：Takuma Watanabe、Yuichiro Mutoh、Shinichi Saito

  DOI：10.1039/c9ob02363a

  日期：——

  A ruthenium-catalyzed cycloisomerization of 3-amino-4-alkynyl-2H-chromen-2-ones via 1,2-carbon migration was developed. Various 1-arylchromeno[3,4-b]pyrrol-4(3H)-ones were synthesized in good to excellent yields. The reaction was applied to the formal total synthesis of marine natural products Ningalin B and Lamellarin H. The efficient synthesis of γ-butyrolactone-fused pyrrole derivatives was also

  通过1，2-碳迁移，开发了钌催化的3-氨基-4-炔基-2 H-铬原子-2-酮的环异构化反应。合成了各种1-芳基色[3,4- b ]吡咯-4（3 H）-，收率良好。该反应用于海洋天然产物宁格林B和Lamellarin H的正式全合成。还实现了γ-丁内酯融合的吡咯衍生物的有效合成。
• Jackson, Yvette A., Heterocycles, 1995, vol. 41, # 9, p. 1979 - 1986
  作者：Jackson, Yvette A.

  DOI：——

  日期：——