1-(3,3-Dimethyl-2,3-dihydro-benzo[b]thiophen-5-yl)-ethanone | 132102-34-2

• 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: 1-(3,3-Dimethyl-2,3-dihydro-benzo[b]thiophen-5-yl)-ethanone
• 英文别名: 1-(3,3-dimethyl-2H-1-benzothiophen-5-yl)ethanone
• CAS: 132102-34-2
• 化学式: C₁₂H₁₄OS
• 分子量: 206.309
• InChiKey: QFJSDFHEUBYCTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3,3-Dimethyl-2,3-dihydro-benzo[b]thiophen-5-yl)-ethanone 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 24.0h， 生成 1-(2,3-dihydro-3,3-dimethylbenzothien-5-yl)ethanol
  参考文献：
  名称：

  新型杂芳类化合物：合成和生物活性。

  摘要：

  在这项研究中，合成了13种杂芳类化合物。每种制备方法中的关键步骤是适当的苯并噻吩基，苯并噻吩基取代的苯并二氢吡喃取代的磷叶立德与相应的nium盐的独立合成得到的缩合，与所选的多烯取代的醛酯缩合。这些杂环中的九个包含硫代苯并二氢吡喃基团，两个具有苯并二氢吡喃基团，另外两个具有苯并噻吩基系统。用两种测定法之一筛选化合物。一种测定法测定了类维生素A抑制佛波酯诱导的小鼠表皮鸟氨酸脱羧酶（ODC）活性增加的能力。另一种测定法测定了类维生素A诱导的人肌样白血病细胞系HL-60的分化。在ODC分析中，筛选了所有13种化合物。活性最高的杂芳烃类化合物是酯10 [甲基（E）-4- [2-（2,2,4,4-四甲基硫代苯并吡喃-6-基）-1-丙烯基]苯甲酸酯]和酸11 [（E）-4- [2-（2,2,4,4-四甲基-3,4-二氢-2H-1-苯并噻喃-6-基）-1-丙烯基]苯甲酸]。这两种类维生素A的ID50值（

  DOI：

  10.1021/jm00105a065
• 作为产物：
  描述：

  2-methyl-1-(phenylthio)propan-2-ol 在 三氯化铝 作用下， 以 二硫化碳 为溶剂， 反应 5.0h， 生成 1-(3,3-Dimethyl-2,3-dihydro-benzo[b]thiophen-5-yl)-ethanone
  参考文献：
  名称：

  新型杂芳类化合物：合成和生物活性。

  摘要：

  在这项研究中，合成了13种杂芳类化合物。每种制备方法中的关键步骤是适当的苯并噻吩基，苯并噻吩基取代的苯并二氢吡喃取代的磷叶立德与相应的nium盐的独立合成得到的缩合，与所选的多烯取代的醛酯缩合。这些杂环中的九个包含硫代苯并二氢吡喃基团，两个具有苯并二氢吡喃基团，另外两个具有苯并噻吩基系统。用两种测定法之一筛选化合物。一种测定法测定了类维生素A抑制佛波酯诱导的小鼠表皮鸟氨酸脱羧酶（ODC）活性增加的能力。另一种测定法测定了类维生素A诱导的人肌样白血病细胞系HL-60的分化。在ODC分析中，筛选了所有13种化合物。活性最高的杂芳烃类化合物是酯10 [甲基（E）-4- [2-（2,2,4,4-四甲基硫代苯并吡喃-6-基）-1-丙烯基]苯甲酸酯]和酸11 [（E）-4- [2-（2,2,4,4-四甲基-3,4-二氢-2H-1-苯并噻喃-6-基）-1-丙烯基]苯甲酸]。这两种类维生素A的ID50值（

  DOI：

  10.1021/jm00105a065

文献信息

• SPRUCE, LYLE W.;GALE, JONATHAN B.;BERLIN, K. DARRELL;VERMA, A. K.;BREITMA+, J. MED. CHEM., 34,(1991) N, C. 430-439
  作者：SPRUCE, LYLE W.、GALE, JONATHAN B.、BERLIN, K. DARRELL、VERMA, A. K.、BREITMA+

  DOI：——

  日期：——
• Novel heteroarotinoids: synthesis and biological activity
  作者：Lyle W. Spruce、Jonathan B. Gale、K. Darrell Berlin、A. K. Verma、Theodore R. Breitman、Xinhua Ji、Dick Van der Helm

  DOI：10.1021/jm00105a065

  日期：1991.1

  HL-60. In the ODC assay, all thirteen compounds were screened. The most active heteroarotinoids were ester 10 [methyl (E)-4-[2-(2,2,4,4-tetramethylthiochroman-6-yl)-1- propenyl]benzoate] and acid 11 [(E)-4-[2-(2,2,4,4-tetramethyl-3,4- dihydro-2H-1- benzothiopyran-6-yl)-1-propenyl]benzoic acid]. Both of these retinoids had ID50 values (dose required for half-maximal inhibition of phorbol ester induced

  在这项研究中，合成了13种杂芳类化合物。每种制备方法中的关键步骤是适当的苯并噻吩基，苯并噻吩基取代的苯并二氢吡喃取代的磷叶立德与相应的nium盐的独立合成得到的缩合，与所选的多烯取代的醛酯缩合。这些杂环中的九个包含硫代苯并二氢吡喃基团，两个具有苯并二氢吡喃基团，另外两个具有苯并噻吩基系统。用两种测定法之一筛选化合物。一种测定法测定了类维生素A抑制佛波酯诱导的小鼠表皮鸟氨酸脱羧酶（ODC）活性增加的能力。另一种测定法测定了类维生素A诱导的人肌样白血病细胞系HL-60的分化。在ODC分析中，筛选了所有13种化合物。活性最高的杂芳烃类化合物是酯10 [甲基（E）-4- [2-（2,2,4,4-四甲基硫代苯并吡喃-6-基）-1-丙烯基]苯甲酸酯]和酸11 [（E）-4- [2-（2,2,4,4-四甲基-3,4-二氢-2H-1-苯并噻喃-6-基）-1-丙烯基]苯甲酸]。这两种类维生素A的ID50值（
• 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.