Ethyl 4-[(2,2,4,4-tetramethylthiochroman-6-yl)carbamothioylamino]benzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Ethyl 4-[(2,2,4,4-tetramethylthiochroman-6-yl)carbamothioylamino]benzoate
• 英文别名: ethyl 4-[(2,2,4,4-tetramethyl-3H-thiochromen-6-yl)carbamothioylamino]benzoate
• 化学式: C₂₃H₂₈N₂O₂S₂
• 分子量: 428.62
• InChiKey: UWRJJFOQSSAVSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,2,4,4-tetramethylthiochroman 在 硝酸 、 乙酸酐 、 铁粉 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 37.5h， 生成 Ethyl 4-[(2,2,4,4-tetramethylthiochroman-6-yl)carbamothioylamino]benzoate
  参考文献：
  名称：

  Synthesis of Flexible Sulfur-Containing Heteroarotinoids That Induce Apoptosis and Reactive Oxygen Species with Discrimination between Malignant and Benign Cells

  摘要：

  Regulation of growth, differentiation, and apoptosis by synthetic retinoids can occur through mechanisms that are dependent and independent of their ability to bind and activate nuclear retinoic acid receptors. The objective of this study was to determine if increasing flexibility of the heteroarotinoid structure would affect the specificity of the synthetic retinoids for the receptors and for their regulation of cancerous and nonmalignant cells. Methods were developed to produce the first examples of heteroarotinoids 15a-15h, which contain urea and/or thiourea linking groups between two aryl rings. Substituents at the para position of the single phenyl ring were either an ester, a nitro group, or a sulfonamide group. Ovarian cancer cell lines Caov-3, OVCAR-3, SK-OV-3, UCI-101, and 222 were utilized, and the inhibitory prowess of the heteroarotinoids was referenced to that of 4-HPR (25). Similar to 4-HPR (25), the heteroarotinoids inhibited growth of all cell lines at micromolar concentrations. Although the heteroarotinoids did not activate retinoic acid receptors, the agents induced potent growth inhibition against the cancer cells with weak activity against normal and benign cells. The growth inhibition was associated with cell loss and induction of reactive oxygen species.

  DOI：

  10.1021/jm030346v

文献信息

• Novel Heteroarotinoids as Potential Antagonists of <i>Mycobacterium</i> <i>b</i><i>ovis</i> BCG
  作者：Chad W. Brown、Shengquan Liu、Jozef Klucik、K. Darrell Berlin、Patrick J. Brennan、Devinder Kaur、Doris M. Benbrook

  DOI：10.1021/jm0303453

  日期：2004.2.1

  A series of 15 heteroarotinoids has been prepared and evaluated for activity against Mycobacterium bovis BCG with the thiourea-containing isoxyl (7) (0.5 mug/mL) as the standard. 2,2,4-Trimethyl-2H-chromen-7-yl 4-(methoxycarbonyl)benzoate (8) displayed the most significant activity (2.0-4.0 mug/mL) in terms of the lowest concentration (mug/mL) (MIC, minimum inhibitory concentration) required to produce a 99% reduction in the number of colonies on a plate as compared to that system free of the agent at the same dilution of the culture suspension. Ethyl 4-[N-(2,2,4,4-tetramethylchroman-6-yl)thiocarbamoyl] amino}benzoate (9) and [(1E,3Z,5E)-1-aza-4-methyl-6-(1,2,2,4-tetramethyl(1,2-dihydroquinolyl))hexa-1,3,5-trienyl]-amino}aminomethane-1-thione (10) exhibited activity at 5.0-10.0 and 10.0-20.0 mug/mL, respectively, while the other examples had MIC values of 20 mug/mL or greater. The inhibitory ability of 8 may occur via the inhibition of mycolic acid synthesis in a like manner as found with 7, but this requires further study. The heteroarotinoids are the first examples to exhibit inhibitory ability against the growth of Mycobacterium bovis BCB.
• US7612107B2
  申请人：——

  公开号：US7612107B2

  公开（公告）日：2009-11-03
• Synthesis of Flexible Sulfur-Containing Heteroarotinoids That Induce Apoptosis and Reactive Oxygen Species with Discrimination between Malignant and Benign Cells
  作者：Shengquan Liu、Chad W. Brown、K. Darrell Berlin、Aridam Dhar、Suresh Guruswamy、David Brown、Ginger J. Gardner、Michael J. Birrer、Doris M. Benbrook

  DOI：10.1021/jm030346v

  日期：2004.2.1

  Regulation of growth, differentiation, and apoptosis by synthetic retinoids can occur through mechanisms that are dependent and independent of their ability to bind and activate nuclear retinoic acid receptors. The objective of this study was to determine if increasing flexibility of the heteroarotinoid structure would affect the specificity of the synthetic retinoids for the receptors and for their regulation of cancerous and nonmalignant cells. Methods were developed to produce the first examples of heteroarotinoids 15a-15h, which contain urea and/or thiourea linking groups between two aryl rings. Substituents at the para position of the single phenyl ring were either an ester, a nitro group, or a sulfonamide group. Ovarian cancer cell lines Caov-3, OVCAR-3, SK-OV-3, UCI-101, and 222 were utilized, and the inhibitory prowess of the heteroarotinoids was referenced to that of 4-HPR (25). Similar to 4-HPR (25), the heteroarotinoids inhibited growth of all cell lines at micromolar concentrations. Although the heteroarotinoids did not activate retinoic acid receptors, the agents induced potent growth inhibition against the cancer cells with weak activity against normal and benign cells. The growth inhibition was associated with cell loss and induction of reactive oxygen species.