4-chloro-5-methyl-9H-xanthen-9-one | 117571-01-4

• 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: 4-chloro-5-methyl-9H-xanthen-9-one
• 英文别名: 5-chloro-4-methyl-9H-xanthen-9-one；5-chloro-4-methylxanthone；4-Chloro-5-methylxanthen-9-one
• CAS: 117571-01-4
• 化学式: C₁₄H₉ClO₂
• 分子量: 244.677
• InChiKey: AJXAMEMJFURCPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-5-methyl-9H-xanthen-9-one 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 甲苯 为溶剂， 生成 R,S-5-chloro-4-(([1-hydroxypropan-2-yl]amino)methyl)-9H-xanthen-9-one
  参考文献：
  名称：

  Promising anticonvulsant and/or analgesic compounds among 5‐chloro‐2‐ or 5‐chloro‐4‐methyl derivatives of xanthone coupled to aminoalkanol moieties—Design, synthesis and pharmacological evaluation

  摘要：

  AbstractA series of 10 aminoalkanol derivatives of 5‐chloro‐2‐ or 5‐chloro‐4‐methylxanthone was synthetized and evaluated for anticonvulsant properties (MES test, mice, intraperitoneal) and compared with neurotoxicity rotarod test (NT, mice, i.p.). The best results both in terms of anticonvulsant activity and protective index value were obtained for 3: 5‐chloro‐2‐([4‐hydroxypiperidin‐1‐yl]methyl)‐9H‐xanthen‐9‐one hydrochloride. Compounds: 1–3, 7 and 10 revealed ED50 values in MES test: 42.78, 31.64, 25.76, 46.19 and 52.50 mg/kg b.w., respectively. 3 showed 70% and 72% of inhibition control specific binding of sigma‐1 (σ1) and sigma‐2 (σ2) receptor, respectively. 3 exhibited also antinociceptive activity at dose 2 mg/kg b.w. after chronic constriction injury in mice. 1, 3, 7 and 10 were evaluated on gastrointestinal flora and proved safe. In genotoxicity test (UMU‐Chromotest) compounds 1, 7 and 10 proved safe at dose 150–300 μg/ml. The pharmacokinetic analysis showed rapid absorption of all studied molecules from the digestive tract (tmax = 5–30 min). The bioavailability of the compounds ranged from 6.6% (1) to 16% (10). All studied compounds penetrate the blood–brain barrier with brain to plasma ratios varied from 4.15 (3) to 7.6 (compound 7), after i.v. administration, and from 1 (7) to 5.72 (3) after i.g. administration.

  DOI：

  10.1111/cbdd.14102
• 作为产物：
  描述：

  2,3-dichlorobenzoic acid sodium salt 在 polyphosphate ester 、 三(3,6-二氧杂庚基)胺 、 copper(l) chloride 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-chloro-5-methyl-9H-xanthen-9-one
  参考文献：
  名称：

  Potential antitumor agents. 58. Synthesis and structure-activity relationships of substituted xanthenone-4-acetic acids active against the colon 38 tumor in vivo

  摘要：

  In a search for compounds related to flavoneacetic acid with activity against solid tumors, a series of methyl-, methoxy-, chloro-, nitro-, and hydroxy-substituted xanthenone-4-acetic acids have been synthesized and evaluated against subcutaneously implanted colon adenocarcinoma 38 in vivo, using a short-term histology assay as a primary screening system. A major goal of this work was to identify compounds with similar profiles of activity to that of flavoneacetic acid but of higher potency. The level of activity of the compounds appeared to depend more on the nature of the substituent than its positioning, in the order Cl greater than Me, OMe greater than NO2, OH. However, the potency of the compounds was related much more to the position rather than the nature of the substitution, with 5-substituted compounds being clearly the most dose potent. 5-Methylxanthenone-4-acetic acid has a similar level of activity to that of flavoneacetic acid in the test systems employed but is more than 7-fold as dose potent.

  DOI：

  10.1021/jm00124a012

文献信息

• Design, synthesis and activity against <i>Staphylococcus epidermidis</i> of 5‐chloro‐2‐ or 5‐chloro‐4‐methyl‐9 <i>H</i> ‐xanthen‐9‐one and some of its derivatives
  作者：Gabriela Mazur、Iwona Skiba‐Kurek、Elżbieta Karczewska、Katarzyna Pańczyk‐Straszak、Joanna Jaworska、Anna M. Waszkielewicz

  DOI：10.1111/cbdd.13803

  日期：2021.3

  derivatives have been designed and synthesized for their potential antibacterial activity. All compounds have been screened against Staphylococcus epidermidis strains ATCC 12228 and clinical K/12/8915. The highest antibacterial activity was observed for compound 3: 5‐chloro‐2‐((4‐(2‐hydroxyethyl)piperazin‐1‐yl)methyl)‐9H‐xanthen‐9‐one dihydrochloride, exhibiting MIC of 0.8 µg/ml against ATCC 12228

  十种新的氧杂蒽酮衍生物因其潜在的抗菌活性而被设计和合成。所有化合物均已针对表皮葡萄球菌菌株 ATCC 12228 和临床 K/12/8915进行筛选。化合物3 的抗菌活性最高：5-氯-2-((4-(2-羟乙基)哌嗪-1-基)甲基)-9 H -xanthen-9-one 二盐酸盐，MIC 为 0.8 µg/与利奈唑胺 (0.8 µg/ml)、环丙沙星 (0.2 µg/ml) 或甲氧苄氨嘧啶和磺胺甲恶唑 (0.8 µg/ml) 相比。对于活性最强的化合物3，使用鼠伤寒沙门氏菌血清型进行遗传毒性试验显示在 75 µg/ml 浓度下的遗传毒性和所有更高浓度下对沙门氏菌的抗菌活性方面的安全性。化合物3皮肤代谢的最终计算机预测似乎很有希望，表明氧杂蒽酮部分在代谢过程中的稳定性。
• Novel xanthone derivatives as potent sirtuin 2 inhibitors
  作者：Gabriela Mazur、Katarzyna Pańczyk-Straszak、Karolina Krysińska、Karolina Niemiec、Anna Waszkielewicz

  DOI：10.1016/j.bmcl.2024.129620

  日期：2024.3

  tertiary piperazine derivatives. The tested compounds do not possess additional SIRT1 activating activity and no antioxidant activity (DPPH in vitro assay). Comprehensive analysis of the lipophilicity of the obtained compounds was also performed. For compound 3 potential molecular targets and similar active compounds were predicted in order to facilitate further research in this group of compounds.

  通过化学合成得到了六种氧杂蒽酮的氨基衍生物。生化研究表明，它们的 SIRT2 抑制活性范围为 48.5 %（化合物4 , 5-氯-2-((4-(3-甲氧基苯基)哌嗪-1-基)甲基)-9H-xanthen-9-one 盐酸盐）到 93.2 ％(化合物3，5-氯-2-(((2-甲氧基苯乙基)氨基)甲基)-9H-呫吨-9-酮盐酸盐)。结构-活性分析显示仲胺相对于叔哌嗪衍生物具有有利的性质。测试的化合物不具有额外的 SIRT1 激活活性，并且没有抗氧化活性（DPPH体外测定）。还对所得化合物的亲脂性进行了综合分析。对于化合物3，预测了潜在的分子靶点和类似的活性化合物，以促进对该组化合物的进一步研究。