2-(4-chlorophenyl)-1-(2,3,4-trihydroxyphenyl)ethanone | 227094-97-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 2-(4-chlorophenyl)-1-(2,3,4-trihydroxyphenyl)ethanone
• 英文别名: 2-(4-chlorophenyl)-2',3',4'-trihydroxyacetophenone
• CAS: 227094-97-5
• 化学式: C₁₄H₁₁ClO₄
• 分子量: 278.692
• InChiKey: VHNHVUUGDDIUFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-chlorophenyl)-1-(2,3,4-trihydroxyphenyl)ethanone 在 硫酸 、 水 、 potassium acetate 作用下， 以 乙醇 为溶剂， 反应 8.5h， 生成 3-(4-Chloro-phenyl)-7,8-dihydroxy-2-methyl-chromen-4-one
  参考文献：
  名称：

  糖原合酶的小分子抑制剂的发现和开发。

  摘要：

  糖原的过度积累是各种糖原贮积病（GSD）的标志，包括庞贝病，科里病，安徒生病和拉福拉病。越来越多的证据表明，抑制糖原累积代表了治疗这些GSD的潜在治疗方法。使用设计用于筛选关键糖原合成酶，糖原合成酶（GS）抑制剂的荧光偏振分析，我们确定了取代的咪唑（rac）-2-甲氧基-4-（1-（2-（1-（1-甲基吡咯烷酮- （2-基）乙基）-4-苯基-1H-咪唑-5-基）苯酚（H23），是酵母GS 2（yGsy2p）的首批抑制剂。来自X射线晶体学在2.85Å处的数据以及动力学数据表明，H23结合在yGsy2p的尿苷二磷酸葡萄糖结合口袋中。直接与H23接触的人与酵母GS之间残基的高度保守性有助于开发约500种H23类似物。这些类似物产生了结构-活性关系图，从而鉴定了取代的吡唑4-（4-（4-羟苯基）-3-（三氟甲基）-1H-吡唑-5-基）邻苯三酚和300-对人GS的效力提高了两倍。这些取代的吡唑具有有

  DOI：

  10.1021/acs.jmedchem.9b01851
• 作为产物：
  描述：

  在 盐酸 作用下， 生成 2-(4-chlorophenyl)-1-(2,3,4-trihydroxyphenyl)ethanone
  参考文献：
  名称：

  Structure–activity relationship studies of flavonoids as potent inhibitors of human platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2

  摘要：

  Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavanones tend to select against 12-hLO, that isoflavans tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.036

文献信息

• The synthesis, structure and activity evaluation of pyrogallol and catechol derivatives as Helicobacter pylori urease inhibitors
  作者：Zhu-Ping Xiao、Tao-Wu Ma、Wei-Chang Fu、Xiao-Chun Peng、Ai-Hua Zhang、Hai-Liang Zhu

  DOI：10.1016/j.ejmech.2010.08.015

  日期：2010.11

  Some pyrogallol and catechol derivatives were synthesized, and their urease inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor, as positive control. The assay results indicate that many compounds have showed potential inhibitory activity against H. pylori urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol (2a) was found to be the most potent

  合成了一些邻苯三酚和邻苯二酚衍生物，并使用众所周知的幽门螺杆菌脲酶抑制剂乙酰氧肟酸（AHA）作为阳性对照，评估了它们对脲酶的抑制活性。测定结果表明许多化合物已显示出对幽门螺杆菌脲酶的潜在抑制活性。已发现4-（4-羟基苯乙基）phen-1,2-二醇（2a）是最有效的脲酶抑制剂，提取分数的IC 50值为1.5±0.2μM，完整细胞的IC 50值为4.2±0.3μM，至少10分别比AHA低2倍和20倍（IC 50为17.2±0.9μM，100.6±13μM）。这一发现表明2a潜在的脲酶抑制剂将值得进一步研究。为了理解所观察到的良好活性，进行了2a到幽门螺杆菌脲酶活性位点的分子对接。
• Synthesis, biological evaluation and structure-activity relationship of a novel class of PI3Kα H1047R mutant inhibitors
  作者：Ning Zhang、Zhimei Yu、Xiaohong Yang、Yan Zhou、Jia Wang、Shao-Lin Zhang、Ming-Wei Wang、Yun He

  DOI：10.1016/j.ejmech.2018.09.002

  日期：2018.10

  treatment. As our continuing endeavor to discover isoform and/or mutant selective class of PI3K inhibitors, herein we report the optimization of a structurally novel PI3Kα H1047R mutant inhibitor Hit-02 (EC50 = 115.3 μM), which was identified from a high-throughput screening campaign. Structure-activity relationship analysis enabled us to discover compound 7h, which strongly inhibited PI3Kα H1047R

  磷脂酰肌醇3-激酶α（PI3Kα）是最有吸引力的癌症治疗靶标之一。作为我们不断努力发现PI3K抑制剂的同工型和/或突变体选择性类别的方法，我们在此报告了对结构新颖的PI3KαH1047R突变体抑制剂Hit-02（EC 50  = 115.3μM）的优化，该结构已通过高通量筛选确定活动。结构-活性关系分析使我们能够发现化合物7h，该化合物强烈抑制PI3KαH1047R突变体，其EC 50值为0.55μM ，效力比Hit-02高200倍以上，而对其他PI3K亚型的影响很小。Western blotting检测表明7h降低AKT的磷酸化水平，这是7h抑制PI3KαH1047R突变体功能的另一个证据。细胞活力测定显示7h抑制HCT-116癌细胞的生长，IC 50值为10.9μM。另外，发现7h使细胞周期停滞在G2期，但未显示任何细胞凋亡作用。此外，7h明显诱导细胞自噬，可能有助于其在癌细胞中的抗增
• Discovery of Novel 2′,3′,4′-Trihydroxy-2-phenylacetophenone Derivatives as Anti-Gram-Positive Antibacterial Agents
  作者：Hideyuki GOTO、Yuji KUMADA、Hitoshi ASHIDA、Ken-ichi YOSHIDA

  DOI：10.1271/bbb.80532

  日期：2009.1.23

  A number of 2′,3′,4′-trihydroxy-2-phenylacetophenone derivatives were synthesized and examined for growth inhibition of several kinds of bacteria. 2′,3′,4′-Trihydroxy-2-phenylacetophenone itself exhibited no antibacterial activity, but some of its derivatives showed various antibacterial activities depending on functional groups introduced on the 2-phenyl ring. Eighteen out of 24 compounds synthesized in this study appeared to possess antibacterial activities against at least two Gram-positive strains of Bacillus subtilis and Staphylococcus aureus, 2-(biphenyl-4-yl)-2′,3′,4′-trihydroxyacetophenone being the most active with LC50 of 5.8 μm and 5.6 μm respectively. However, none of the synthesized compounds exhibited inhibitory effects on Gram-negative strains, such as Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Salmonella enterica, suggesting that anti-Gram-positive specificity of the antibacterial compounds.

  研究人员合成了一些 2′,3′,4′-三羟基-2-苯基苯乙酮衍生物，并考察了它们对几种细菌生长的抑制作用。2′,3′,4′-三羟基-2-苯基苯乙酮本身没有抗菌活性，但它的一些衍生物根据在 2-苯基环上引入的官能团的不同而表现出不同的抗菌活性。在本研究合成的 24 种化合物中，有 18 种似乎对至少两种革兰氏阳性菌株枯草杆菌和金黄色葡萄球菌具有抗菌活性，其中 2-（联苯-4-基）-2′,3′,4′-三羟基苯乙酮的活性最高，半数致死浓度分别为 5.8 μm 和 5.6 μm。然而，合成的化合物均未对革兰氏阴性菌株（如大肠杆菌、变形杆菌、铜绿假单胞菌和肠炎沙门氏菌）产生抑制作用，这表明这些抗菌化合物具有抗革兰氏阳性菌的特异性。
• Metronidazole-Deoxybenzoin Derivatives as Anti-Helicobacter pylori Agents with Potent Inhibitory Activity against HPE-Induced Interleukin-8
  作者：Yin Luo、Huan-Qiu Li、Yang Zhou、Zi-Lin Li、Tao Yan、Hai-Liang Zhu

  DOI：10.1002/cmdc.201000126

  日期：——

  of new metronidazole–deoxybenzoin derivatives were synthesized and evaluated for their antimicrobial activity against Helicobacter pylori. Highly selective anti‐H. pylori activity was also observed in synthesized compounds. Compound 34 exhibited the most potent activity, similar to the positive control amoxicillin. Furthermore, compounds 17 and 34 were able to significantly decrease H. pylori water

  合成了一系列新的甲硝唑-脱氧安息香衍生物，并评估了它们对幽门螺杆菌的抗菌活性。在合成的化合物中还观察到了高度选择性的抗幽门螺杆菌活性。与阳性对照阿莫西林相似，化合物34显示出最有效的活性。此外，化合物17和34能够显着降低幽门螺杆菌水提取物（HPE）诱导的胃粘膜细胞白细胞介素8（IL-8）的产生，但对细胞活力没有任何影响。
• Design and synthesis of novel deoxybenzoin derivatives as FabH inhibitors and anti-inflammatory agents
  作者：Huan-Qiu Li、Yin Luo、Peng-Cheng Lv、Lei Shi、Chang-Hong Liu、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2010.01.032

  日期：2010.3

  described in this Letter. Potent FabH inhibitory and selective anti-Gram-negative bacteria activities were observed in deoxybenzoin derivatives. Furthermore, compound 19 was able to reduce the ECE-induced IL-8 production in gastric mucosal cells significantly. Based on the biological data and molecular docking, compound 19 is a potential FabH inhibitor and anti-inflammatory agent deserving further research

  β-酮酰基-酰基载体蛋白合酶III（FabH）在大多数细菌中通过II型脂肪酸合酶催化脂肪酸生物合成的起始步骤。这种必需酶的重要作用，加上其独特的结构特征和在细菌中的普遍存在，使其成为开发新型FabH抑制剂的有吸引力的新靶标。该信中描述了卤化物-脱氧苯偶姻衍生物的合成和生物学评价。在脱氧安息香衍生物中观察到强效的FabH抑制活性和选择性的抗革兰氏阴性细菌活性。此外，化合物19能够显着降低ECE诱导的胃粘膜细胞中IL-8的产生。根据生物学数据和分子对接，化合物19 是潜在的FabH抑制剂和抗炎药，值得进一步研究。