6-Acetoxychromone-3-aldehyde | 69155-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-Acetoxychromone-3-aldehyde
• 英文别名: 6-acetoxy-3-formylchromone；6-acetoxy-4-oxo-4H-chromene-3-carbaldehyde；6-Acetoxychromon-3-carbaldehyd；3-formyl-4-oxo-4H-chromen-6-yl acetate；(3-formyl-4-oxochromen-6-yl) acetate
• CAS: 69155-77-7
• 化学式: C₁₂H₈O₅
• mdl: MFCD08445353
• 分子量: 232.193
• InChiKey: LEBXNPPDAKBRIZ-UHFFFAOYSA-N

物化性质

• 沸点：
  395.1±42.0 °C(Predicted)
• 密度：
  1.457±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  6-Acetoxychromone-3-aldehyde 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 6-羟基-4-氧代-4H-色烯-3-甲醛
  参考文献：
  名称：

  Inhibition of Alzheimer’s BACE-1 by 2,6-dialkyl-4-chromon-3-yl-1,4-dihydropyridine-3,5-dicarboxylates

  摘要：

  Alzheimer's disease is the most common cause of dementia in the elderly, and no disease-modifying therapy is yet available for this devastating pathology. Deposition of different physicochemical forms of amyloid-beta peptides is a critical phase in the pathogenesis of Alzheimer's disease. beta-Site amyloid precursor protein cleaving enzyme 1 (BACE-1) is a major enzyme responsible for amyloid-beta production; therefore, inhibition of this enzyme represents a promising approach for the discovery of amyloid-beta-lowering agents. In this study, a series of novel 2,6-dialkyl-4-chromon-3-yl-1,4-dihydropyridine-3,5-dicarboxylates (14-23) were synthesized and assessed as BACE-1 inhibitors using the Forster resonance energy transfer-based enzyme assay. Synthesized dihydropyridines exhibited weak-to-relatively-good BACE-1 inhibitory activities. Enzyme inhibitory activities ranged from 6.84 +/- A 6.62 (23) to 51.32 +/- A 1.04 (14) percent enzyme inhibitions at the concentration of 10 mu M. The structure-activity relationship study showed that the presence of 4-[7-(ethanoyloxy)-4-oxo-4H-chromen-3-yl] moiety at C4 position of dihydropyridine ring (14, 16 and 18) confers higher activity compared with other substitutions at this position. Docking simulation predicted a key H-bond interaction between Asp32 residue and dihydropyridine NH group. Moreover, all docked dihydropyridines made good hydrophobic contacts with S1 and S2 subpockets of BACE-1. A good correlation between estimated binding affinities (pK(i)) and experimental BACE-1 inhibitory activities at 10 mu M was obtained (R (2) = 0.639). The findings of this study suggested that 2,6-dialkyl-4-chromon-3-yl-1,4-dihydropyridine-3,5-dicarboxylates could be promising scaffolds for the discovery of novel BACE-1 inhibitors for management of Alzheimer's disease.

  DOI：

  10.1007/s00044-015-1367-z
• 作为产物：
  描述：

  2,5-二羟基苯乙酮 在 吡啶 、 三氯氧磷 作用下， 反应 19.0h， 生成 6-Acetoxychromone-3-aldehyde
  参考文献：
  名称：

  吡啶-2（1 H）-one衍生物的c-Src激酶抑制活性的合成和评价

  摘要：

  Src激酶是Src激酶家族（SFKs）的原型成员，在各种人类肿瘤中均过表达，已成为抗癌药物设计的目标。从这个角度出发，合成了一系列十八个2-吡啶酮衍生物，并评估了它们的c-Src激酶抑制活性。其中，八种化合物表现出c-Src激酶抑制活性，IC 50值小于25μM。化合物1- [2-（二甲基氨基）乙基] -5-（2-羟基-4-甲氧基苯甲酰基）吡啶-2（1H）-一（36）表现出最高的c-Src激酶抑制作用，IC 50值为12.5μM 。此外，化合物36的激酶抑制活性研究人员针对EGFR，MAPK和PDK进行了研究，但在最高测试浓度（300μM）下未观察到明显的活性。这些结果为进一步优化该支架以设计下一代2-吡啶酮衍生物作为候选Src激酶抑制剂提供了见识。

  DOI：

  10.1016/j.bioorg.2014.02.001

文献信息

• Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives
  作者：Karam Chand、Suchita Prasad、Rakesh K. Tiwari、Amir N. Shirazi、Sumit Kumar、Keykavous Parang、Sunil K. Sharma

  DOI：10.1016/j.bioorg.2014.02.001

  日期：2014.4

  Src kinase, a prototype member of the Src family of kinases (SFKs), is over-expressed in various human tumors, and has become a target for anticancer drug design. In this perspective, a series of eighteen 2-pyridone derivatives were synthesized and evaluated for their c-Src kinase inhibitory activity. Among them, eight compounds exhibited c-Src kinase inhibitory activity with IC50 value of less than

  Src激酶是Src激酶家族（SFKs）的原型成员，在各种人类肿瘤中均过表达，已成为抗癌药物设计的目标。从这个角度出发，合成了一系列十八个2-吡啶酮衍生物，并评估了它们的c-Src激酶抑制活性。其中，八种化合物表现出c-Src激酶抑制活性，IC 50值小于25μM。化合物1- [2-（二甲基氨基）乙基] -5-（2-羟基-4-甲氧基苯甲酰基）吡啶-2（1H）-一（36）表现出最高的c-Src激酶抑制作用，IC 50值为12.5μM 。此外，化合物36的激酶抑制活性研究人员针对EGFR，MAPK和PDK进行了研究，但在最高测试浓度（300μM）下未观察到明显的活性。这些结果为进一步优化该支架以设计下一代2-吡啶酮衍生物作为候选Src激酶抑制剂提供了见识。
• Study of Microwave Irradiation Effect on Condensation of 6-R-3-Formylchromones with Active Methylene Compounds
  作者：Renata Gašparová、Margita Lácová

  DOI：10.1135/cccc19951178

  日期：——

  Condensation of 6-R-3-formylchromones (I) with 3,3-dimethyl-1,3-cyclohexanedione (II), 1,3-indandione (III), 1,2e-biindenylidene-3,1e,3e-trione (bindone, IV), 2-oxo-1,4-benzothiazine (V) and 3-oxo-2,3-dihydro-1-thia-3a,8-diazacyclopent[a]indene (VI) by the "classical" method, as well as condensation in a microwave oven, has been studied. Some subsequent reactions of these products are described.

  6-R-3-甲醛基香豆素（I）与3,3-二甲基-1,3-环己二酮（II）、1,3-茚二酮（III）、1,2e-双茚基-3,1e,3e-三酮（bindone，IV）、2-氧代-1,4-苯并噻嗪（V）和3-氧代-2,3-二氢-1-硫-3a,8-二氮杂环戊烯（VI）的缩合反应，采用“经典”方法以及微波炉中的缩合反应已被研究。这些产物的一些后续反应也被描述。
• Synthesis, reactions and antineoplastic activity of 3-(2-oxo-2H-chromen-3-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromene derivatives
  作者：Renata Gašparová、Pavol Koiš、Margita Lácová、Silvia Kováčová、Andrej Boháč

  DOI：10.2478/s11532-012-0184-1

  日期：2013.4.1

  5-alkoxy-, 5-hydroxy- or 5-acylamino-2H,5H-pyrano[3,2-c]chromen-2-ones 4-6via nucleophilic substitution of acetyloxy group at C-5. Acetates and hydroxyl derivatives 3 and 5 undergo facile rearrangement in an acid medium yielding 5-hydroxypyrano[2,3-b]chromen-2(10aH)-ones 7. Twelve prepared compounds were evaluated on their antineoplastic activities on 60 human tumour cell line panels in NCI USA. The

  摘要 通过 4 环缩合反应，高收率合成了关键的 3-(2-oxo-2H-chromen-3-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromen-5-yl 醋酸酯 3 -oxo-4H-chromen-3-carbaldehydes 1 与香豆素-3-乙酸 2 在温和条件下。反应途径包括羟醛缩合和随后的分子内内酯化，得到 2-氧代-2H,5H-吡喃并[3,2-c]色烯骨架 3。用醇、水或含氮化合物进一步处理乙酸酯 3 生成 5-烷氧基-, 5-羟基-或5-酰氨基-2H,5H-吡喃并[3,2-c]色烯-2-酮4-6通过乙酰氧基在C-5处的亲核取代。乙酸盐和羟基衍生物 3 和 5 在酸性介质中容易重排，产生 5-羟基吡喃并[2,3-b]色烯-2(10aH)-酮 7。在美国 NCI 的 60 个人类肿瘤细胞系面板上评估了 12 种制备的化合物的抗肿瘤活性。所获得的生物学结果证实
• Metal-Free Catalyzed Oxidation/Decarboxylative [3+2] Cycloaddition Sequences of 3-Formylchromones to Access Pyrroles with Anti-Cancer Activity
  作者：Xue Li、Xing-Yu Chen、Bing-Ying Fan、Qun Yu、Jie Lei、Zhi-Gang Xu、Zhong-Zhu Chen

  DOI：10.3390/molecules28227602

  日期：——

  An efficient and direct approach to pyrroles was successfully developed by employing 3-formylchromones as decarboxylative coupling partners, and facilitated by microwave irradiation. The protocol utilizes easily accessible feedstocks, a catalytic amount of DBU without any metals, resulting in high efficiency and regioselectivity. Notably, all synthesized products were evaluated against five different cancer cell lines and compound 3l selectively inhibited the proliferation of HCT116 cells with an IC50 value of 10.65 μM.

  通过使用 3-甲酰基色酮作为脱羧偶联剂，并在微波辐照的帮助下，成功开发出了一种高效、直接的吡咯方法。该方法利用容易获得的原料和催化量的 DBU，不含任何金属，因而具有高效率和区域选择性。值得注意的是，所有合成产物都针对五种不同的癌细胞系进行了评估，化合物 3l 选择性地抑制了 HCT116 细胞的增殖，IC50 值为 10.65 μM。
• Phosphine-catalyzed formal Buchner [6+1] annulation: <i>de novo</i> construction of cycloheptatrienes
  作者：Jingxiong Lai、You Huang

  DOI：10.1039/d3cc04905a

  日期：——

  designed allenoate has been developed, providing a series of cycloheptatriene derivatives in moderate to good yields (up to 99%). This reaction demonstrates that the introduction of an electrophilic allylic group to allenoates effectively extends the reaction scope of phosphine-catalyzed annulation, providing a concise route to cycloheptatrienes. Mechanistic study indicated that this reaction involves

  一种前所未有的膦催化的新设计的联烯酸酯的正式布氏[6+1]成环反应已经被开发出来，以中等至良好的产率（高达99%）提供一系列环庚三烯衍生物。该反应表明，在联烯酸酯中引入亲电烯丙基基团有效地扩展了膦催化环化的反应范围，为环庚三烯提供了一条简洁的路线。机理研究表明，该反应涉及[4+2] Diels-Alder反应和双环[4.1.0]部分的扩环，类似于布赫纳反应。值得注意的是，这种[6+1]环化的对映选择性变体也可以使用手性亚氨基膦催化剂进行。