3-Hydroxy-2-[(2-hydroxy-4,4-dimethyl-6-oxocyclohexen-1-yl)-(5-methylthiophen-2-yl)methyl]-5,5-dimethylcyclohex-2-en-1-one

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3-Hydroxy-2-[(2-hydroxy-4,4-dimethyl-6-oxocyclohexen-1-yl)-(5-methylthiophen-2-yl)methyl]-5,5-dimethylcyclohex-2-en-1-one
• 化学式: C₂₂H₂₈O₄S
• 分子量: 388.528
• InChiKey: MBDHIUHQIMRIFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-methyl-N-[(5-methylthiophen-2-yl)methylideneamino]benzenesulfonamide 、 5,5-二甲基-1,3-环己二酮 以 甲苯 为溶剂， 反应 0.5h， 以84%的产率得到3-Hydroxy-2-[(2-hydroxy-4,4-dimethyl-6-oxocyclohexen-1-yl)-(5-methylthiophen-2-yl)methyl]-5,5-dimethylcyclohex-2-en-1-one
  参考文献：
  名称：

  Transition metal and base free coupling of N-tosylhydrazones with 1,3-dicarbonyl compound

  摘要：

  N-tosylhydrazones derived from a wide variety of aryl, alkyl and heteroaryl aldehydes undergo smooth coupling with 5,5-dimethylcyclohexane-1,3-dione under transition metal and base free conditions to generate tetraketo compounds in high yields. In presence of a base, the coupling reaction generates beta-keto enol ether as the major product in a polar aprotic solvent. N-Tosylhydrazone can also be converted to xanthenedione in high yields in one-pot operation under mild acidic conditions. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2017.02.001

文献信息

• Discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for treating cancers with microsatellite instability
  作者：Hwasun Yang、Miso Kang、Seonyeong Jang、Soo Yeon Baek、Jiwon Kim、Gyeong Un Kim、Dongwoo Kim、Junsu Ha、Jong Seung Kim、Cheulhee Jung、Nam-Jung Kim、Sung-Yup Cho、Woong-Hee Shin、Juyong Lee、Junsu Ko、Ansoo Lee、Gyochang Keum、Sanghee Lee、Taek Kang

  DOI：10.1016/j.bmc.2024.117588

  日期：2024.2

  various cancer types. Recent research has identified Werner syndrome ATP-dependent helicase (WRN) as a promising synthetic lethal target for MSI cancers. Herein, we report the first discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for MSI cancer therapy. Initial computational analysis and biological evaluation identified a new scaffold for a WRN inhibitor. Subsequent

  微卫星不稳定性 (MSI) 是一种由 DNA 错配修复系统缺陷引起的高突变状态，导致各种癌症类型的发展。最近的研究已确定维尔纳综合征 ATP 依赖性解旋酶 (WRN) 是 MSI 癌症的一个有前景的合成致死靶点。在此，我们报告了首次发现噻吩-2-基亚甲基双二甲酮衍生物作为用于 MSI 癌症治疗的新型 WRN 抑制剂。初步计算分析和生物学评估确定了 WRN 抑制剂的新支架。随后的 SAR 研究发现了一种高效的 WRN 抑制剂。此外，我们证明最佳化合物通过抑制 WRN 诱导 MSI 癌细胞 DNA 损伤和细胞凋亡。这项研究为 WRN 抑制剂提供了一种新的药效团，强调了它们对 MSI 癌症的治疗潜力。
• Transition metal and base free coupling of N-tosylhydrazones with 1,3-dicarbonyl compound
  作者：Deepika Choudhary、Chanchal Agrawal、Vineeta Khatri、Ranjit Thakuria、Ashok K. Basak

  DOI：10.1016/j.tetlet.2017.02.001

  日期：2017.3

  N-tosylhydrazones derived from a wide variety of aryl, alkyl and heteroaryl aldehydes undergo smooth coupling with 5,5-dimethylcyclohexane-1,3-dione under transition metal and base free conditions to generate tetraketo compounds in high yields. In presence of a base, the coupling reaction generates beta-keto enol ether as the major product in a polar aprotic solvent. N-Tosylhydrazone can also be converted to xanthenedione in high yields in one-pot operation under mild acidic conditions. (C) 2017 Elsevier Ltd. All rights reserved.