4-ethoxy-7-hydroxycoumarin | 75590-48-6

• 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: 4-ethoxy-7-hydroxycoumarin
• 英文别名: 4-ethoxy-7-hydroxy-2H-chromen-2-one；4-ethoxy-7-hydroxychromen-2-one
• CAS: 75590-48-6
• 化学式: C₁₁H₁₀O₄
• mdl: MFCD04612956
• 分子量: 206.198
• InChiKey: AOSUUEBGVYZPMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-ethoxy-7-hydroxycoumarin 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 1.0h， 生成 7-{2-[4-(4-Chloro-benzyl)-piperazin-1-yl]-ethoxy}-4-hydroxy-chromen-2-one; hydrochloride
  参考文献：
  名称：

  N-Benzylpiperazino derivatives of 3-nitro-4-hydroxycoumarin with H1 antihistamine and mast cell stabilizing properties

  摘要：

  In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release of histamine in rat passive peritoneal anaphylaxis (PPA). The most potent compound, 1-[2-hydroxy-3-[(4-hydroxy-3-nitrocoumarin-7-yl)oxy]propyl]-4- (4-chlorobenzyl)piperazine, 30, had a pA2 of 9.0 against histamine on guinea pig ileum and inhibited histamine release in the rat PPA test with a potency similar to that of disodium cromoglycate.

  DOI：

  10.1021/jm00377a013
• 作为产物：
  描述：

  间苯二酚 在 盐酸 、 三氟化硼乙醚 作用下， 以 甲醇 为溶剂， 反应 25.5h， 生成 4-ethoxy-7-hydroxycoumarin
  参考文献：
  名称：

  Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease

  摘要：

  A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BuChE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BuChE (IC50 values of 80.72 nM for eqBuChE and 112.72 nM for hBuChE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 mu M). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.040

文献信息

• Heterocyclic coumarin derivatives
  申请人：Beecham Group Limited

  公开号：US04263299A1

  公开（公告）日：1981-04-21

  A compound of formula (I): ##STR1## and pharmaceutically acceptable salts thereof, wherein R is hydrogen or an alkyl group containing up to 6 carbon atoms; X is a bond or oxygen; Y is --(CH.sub.2).sub.n -- where n is 0 or an integer from 1 to 5 wherein one carbon atom not bound to the nitrogen atom may be optionally substituted with a hydroxy group; and Z is hydrogen or halogen; may be used in the prophylaxis and treatment of diseases whose symptoms are controlled by the mediators of the allergic response, for example asthma, hay-fever, rhinitis and allergic eczema.

  化合物的结构式（I）：##STR1##及其药学上可接受的盐，其中R是氢或含有最多6个碳原子的烷基基团；X是键或氧；Y是--(CH.sub.2).sub.n--，其中n为0或1至5的整数，其中一个未与氮原子结合的碳原子可以选择性地被羟基取代；Z是氢或卤素；可用于预防和治疗由过敏反应介质控制症状的疾病，例如哮喘、花粉症、鼻炎和过敏性湿疹。
• Heterocyclic coumarin derivatives, their preparation and pharmaceutical compositions comprising said derivatives
  申请人：BEECHAM GROUP PLC

  公开号：EP0010392A1

  公开（公告）日：1980-04-30

  A compound of formula (I): and pharmaceutically acceptable salts thereof, wherein R is hydrogen or an alkyl group containing up to 6 carbon atoms; X is a bond or oxygen; Y is -(CH2)n -where n is 0 or an integer from 1 to 5 wherein one carbon atom not bound to the nitrogen atom may be optionally substituted with a hydroxy group; and Z is hydrogen or halogen; e.g. 1-(4-chlorobenzyl) -4-[3-(4-hydroxy-3-nitro- coumarin-7-yloxy) propyl] piperazine; may be used in the prophylaxis and treatment of diseases whose symptoms are controlled by the mediators of the allergic response, for example asthma, hay-fever, rhinitis and allergic eczema. A compound of formula (I) is prepared by reacting a compound of formula (II) or a salt thereof wherein R, X, Y, and Z are defined with respect to formula (i) with a nitrating agent

  式(I)化合物 及其药学上可接受的盐类，其中 R 是氢或最多含有 6 个碳原子的烷基；X 是键或氧；Y 是-(CH2)n -其中 n 是 0 或 1 至 5 的整数，其中未与氮原子结合的一个碳原子可任选被羟基取代；Z 是氢或卤素；例如：1-(4-氯苄基)-4-[3-(4-羟基-3-硝基香豆素-7-氧基)丙基]哌啶。g. 1-(4-氯苄基)-4-[3-(4-羟基-3-硝基香豆素-7-氧基)丙基]哌嗪；可用于预防和治疗其症状受过敏反应介质控制的疾病，例如哮喘、花粉症、鼻炎和过敏性湿疹。 式（I）化合物是通过式（II）化合物或其盐反应制备的 其中 R、X、Y 和 Z 的定义见式 (i)。
• Coumarin intermediates
  申请人：BEECHAM GROUP PLC

  公开号：EP0050396A1

  公开（公告）日：1982-04-28

  Compounds of the formula (II): or a salt thereof, wherein R is hydrogen or an alkyl group containing up to 6 carbon atoms; X is a covalent bond or oxygen; Y is -(CH2)n- where n is 0 or an integer from 1 to 5 wherein one carbon atom not bound to the nitrogen atom may be optionally substituted with a hydroxy group; and Z is hydrogen or halogen are useful intermediates in the preparation of pharmacologically active compounds described in European Patent Application No 79302141.

  式 (II) 的化合物：或其盐，其中 R 是氢或最多含有 6 个碳原子的烷基；X 是共价键或氧；Y 是-(CH2)n-，其中 n 是 0 或 1 至 5 的整数，其中未与氮原子结合的一个碳原子可任选被羟基取代；Z 是氢或卤素，是制备欧洲专利申请第 79302141 号所述药理活性化合物的有用中间体。
• Design, synthesis and biological evaluation of novel donepezil–coumarin hybrids as multi-target agents for the treatment of Alzheimer’s disease
  作者：Sai-Sai Xie、Jin-Shuai Lan、Xiaobing Wang、Zhi-Min Wang、Neng Jiang、Fan Li、Jia-Jia Wu、Jin Wang、Ling-Yi Kong

  DOI：10.1016/j.bmc.2016.02.023

  日期：2016.4

  Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87 mu M and 0.93 mu M, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37 mu M for hAChE; 1.98 mu M for hBuChE; 2.62 mu M for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit. (C) 2016 Elsevier Ltd. All rights reserved.
• BUCKLE, D. R.;OUTRED, D. J.;SMITH, H.;SPICER, B. A., J. MED. CHEM., 1984, 27, N 11, 1452-1457
  作者：BUCKLE, D. R.、OUTRED, D. J.、SMITH, H.、SPICER, B. A.

  DOI：——

  日期：——