4-formylphenyl 4,4-dimethylchroman-6-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 4-formylphenyl 4,4-dimethylchroman-6-carboxylate
• 英文别名: (4-Formylphenyl) 4,4-dimethyl-2,3-dihydrochromene-6-carboxylate
• 化学式: C₁₉H₁₈O₄
• 分子量: 310.35
• InChiKey: QTCQBLHJEQCXIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  氨基硫脲 、 4-formylphenyl 4,4-dimethylchroman-6-carboxylate 在 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 以78%的产率得到4-formylphenyl 4,4-dimethylchroman-6-carboxylate thiosemicarbazone
  参考文献：
  名称：

  1,3,3-三甲基吲哚-5-胺和4-甲酰基4,4-二甲基苯并-6-羧酸盐硫杂氨基甲酸酯（OHet72）

  摘要：

  （2021年）。1,3,3-Trimethylindolin-5-amine和4-formylphenyl 4,4-Dimethylchroman-6-carboxylate Thiosemicarbazone（OHet72）有机制备和程序，国际：53，第1页，第68-77页。

  DOI：

  10.1080/00304948.2020.1834819
• 作为产物：
  描述：

  ethyl 4,4-dimethylchroman-6-carboxylate 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 27.0h， 生成 4-formylphenyl 4,4-dimethylchroman-6-carboxylate
  参考文献：
  名称：

  1,3,3-三甲基吲哚-5-胺和4-甲酰基4,4-二甲基苯并-6-羧酸盐硫杂氨基甲酸酯（OHet72）

  摘要：

  （2021年）。1,3,3-Trimethylindolin-5-amine和4-formylphenyl 4,4-Dimethylchroman-6-carboxylate Thiosemicarbazone（OHet72）有机制备和程序，国际：53，第1页，第68-77页。

  DOI：

  10.1080/00304948.2020.1834819

文献信息

• Biologically Active Heteroarotinoids Exhibiting Anticancer Activity and Decreased Toxicity
  作者：Doris M. Benbrook、Matora M. Madler、Lyle W. Spruce、Paul J. Birckbichler、Eldon C. Nelson、Shankar Subramanian、G. Mahika Weerasekare、Jonathan B. Gale、Manford K. Patterson,、Binghe Wang、Wei Wang、Shennan Lu、Tami C. Rowland、Paul DiSivestro、Charles Lindamood、Donald L. Hill、K. Darrell Berlin

  DOI：10.1021/jm970196m

  日期：1997.10.1

  A series of retinoids, containing heteroatoms in a cyclic ring and called heteroarotinoids, were synthesized, and their biological activity was evaluated using tissue culture lines that have measurable responses to trans-retinoic acid (t-RA). Transglutaminase (TGase) was assessed in the human erythroleukemia cell line (GM06141A) as an indicator of differentiation and apoptosis. Proliferation was evaluated in a human cervical cell line, CC-1, which exhibits dose-dependent alterations in growth rate in response to treatment with trans-retinoic acid. Activation of nuclear retinoic acid receptors was determined in a reporter cell line established from CC-1. The reporter line, called CC-B, contains a reporter gene controlled by a retinoic acid responsive element (RARE) and a thymidine kinase (tk) promoter. Treatment of the CC-B line with the heteroarotinoids resulted in a dose-responsive and retinoid-dependent regulation of reporter gene expression. The heteroarotinoids exhibited activity in all assays and correlated in a statistically significant manner between assays. RARE transactivation activity in CC-B cells correlated with induction of TGase in GM06141A (R = 0.96) and with a decrease in the growth rate of CC-1 cells (R = -0.90). The ability of the selected heteroarotinoids to induce differentation, inhibit proliferation, and activate nuclear receptors demonstrates the chemotherapeutic potential of these agents. In view of the biological activity cited, an in vivo toxicity study was conducted on male B6D2F1 mice with three heteroarotinoids, namely 8 [(2E,4E,6E)-3,7-dimethyl-7-(1,2,3,4-tetrahydro-4,4-dimethylthio- chroman-6-yl)-2,4,6-heptatrienoic acid], 10 [2E,4E,6E)-3,7-dimethyl-7-(1,2,3,4-tetrahydro-4,4-dimethylchroman-6-yl)-2,4,6-heptatrienoic acid], and 13 [(E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoic acid]. The mice were used with gavage of heteroarotinoids in corn oil [0.1, 0.2, 0.4, or 0.8 mg/kg] and with 0.01 or 0.05 mg/kg of TTNPB (5) [(E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid] as reference controls. The target organs affected in the mice by the three heteroarotinoids were those typically associated with t-RA (1) toxicity. The maximum tolerated dose (MTD) of 13 was 9.4 mg/kg/day, which was equal in toxicity to that of t-RA (1) and 1000-fold less toxic than TTNPB (5). The MTDs of 8 and 10 were 34 and 32 mg/kg/day, respectively, which is 3-fold less toxic than t-RA (1) and 3000-fold less toxic than TTNPB (5). The 3000-fold reduced toxicity, compared with only a 27% reduction biological activity of 8 and 10 with respect to that of TTNPB, observed in our assays indicates a good therapeutic ratio of these heteroarotinoids over the parent compound. The biological activity and reduced toxicity of these heteroarotinoids demonstrate the potential efficacy as anticancer agents.
• 1,3,3-Trimethylindolin-5-amine and 4-Formylphenyl 4,4-Dimethylchroman-6-carboxylate Thiosemicarbazone (OHet72)
  作者：Daniel J. Bryant、K. Darrell Berlin、Richard A. Bunce

  DOI：10.1080/00304948.2020.1834819

  日期：2021.1.2

  (2021). 1,3,3-Trimethylindolin-5-amine and 4-Formylphenyl 4,4-Dimethylchroman-6-carboxylate Thiosemicarbazone (OHet72) Organic Preparations and Procedures International: Vol. 53, No. 1, pp. 68-77.

  （2021年）。1,3,3-Trimethylindolin-5-amine和4-formylphenyl 4,4-Dimethylchroman-6-carboxylate Thiosemicarbazone（OHet72）有机制备和程序，国际：53，第1页，第68-77页。