2,2-dimethyl-3-phenyl-7-methoxychromene | 213844-39-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 2,2-dimethyl-3-phenyl-7-methoxychromene
• 英文别名: 7-methoxy-2,2-dimethy-3-phenyl-2H-chromene；2,2-dimethyl-3-phenyl-7-methoxy-3-chromene；7-Methoxy-2,2-dimethyl-3-phenylchromene
• CAS: 213844-39-4
• 化学式: C₁₈H₁₈O₂
• 分子量: 266.34
• InChiKey: UYZVYCFTGZJRSH-UHFFFAOYSA-N

物化性质

• 沸点：
  383.0±41.0 °C(Predicted)
• 密度：
  1.086±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-3-phenyl-7-methoxychromene 在 aluminum (III) chloride 作用下， 以 正己烷 、 异丙醇 为溶剂， 反应 3.17h， 生成 N,N-diethyl-2-[(2S,3S)-6-methoxy-1,1-dimethyl-2,3-diphenyl-indan-4-yl]oxy-ethanamine
  参考文献：
  名称：

  Synthesis and biological evaluation of trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxyalkylamine derivatives against drug susceptible, non-replicating M. tuberculosis H37Rv and clinical multidrug resistant strains

  摘要：

  Synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of Mycobacterium tuberculosis have been reported. All the new compounds in the series exhibited MIC between 1.56 and 6.25 mu g/ml. Two compounds 1i and 1j with low MIC and low cytotoxicity showed significant reduction in CFU in infected mouse macrophages at 1 x MIC concentration. The compound 1i inhibited the growth of M. tuberculosis in mice at 100 mg/kg dose with 1.35 log(10) reduction of CFU in lungs tissue and was active against non-replicating Mycobacterium tuberculosis under anaerobic condition. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.030
• 作为产物：
  描述：

  7-甲氧基-3-苯基-2H-色烯-2-酮 以82的产率得到2,2-dimethyl-3-phenyl-7-methoxychromene
  参考文献：
  名称：

  [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF TRANS 3,4- DIARYLCHROMAN AND THEIR DERIVATIVES
  [FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE 3,4- DIARYLCHROMANE ET LEURS DÉRIVÉS

  摘要：

  该发明描述了一种改进和优越的制备过程，用于制备反避孕、抗骨质疏松和乳腺癌药物的类似物，其中包括转型3,4-二芳基色基烷和其衍生物。在Lewis酸存在下，芳烃与2,2-二烷基-3-芳基色基烷缩合，仅生成反式-3,4-二芳基-2,2-二烷基色基烷。因此，通过苯酚与2,2-二甲基-3-苯基色基烷的氢化芳基化反应，优良的收率得到了Ormeloxifene的前体反式-2,2-二甲基-3-苯基-4-(4-羟基苯基)色基烷。

  公开号：

  WO2009078029A2

文献信息

• Design and synthesis of ERα/ERβ selective coumarin and chromene derivatives as potential anti-breast cancer and anti-osteoporotic agents
  作者：M. Kamil Hussain、M. Imran Ansari、N. Yadav、Puneet K. Gupta、A. K. Gupta、R. Saxena、I. Fatima、M. Manohar、P. Kushwaha、V. Khedgikar、J. Gautam、Ruchir Kant、P. R. Maulik、R. Trivedi、A. Dwivedi、K. Ravi Kumar、A. K. Saxena、K. Hajela

  DOI：10.1039/c3ra45749d

  日期：——

  Several new coumarin and chromene prototype derivatives have been synthesised and evaluated for their ERα and ERβ selective activity. Coumarin prototype compounds 18 & 19 were found to be ERα selective and the most active, exhibiting potential antiproliferative activity against both ER +ve & ER −ve breast cancer cell lines. The surprise finding of the series, however, are the novel prototype III chromenes 45 & 46, with aroyl substitution at the 6th position. Both the compounds have shown potent antiproliferative activity against both the breast cancer cell lines, promote alkaline phosphatase activity, enhance osteoblast mineralization in vitro, significantly decrease ERE–ERα dependent transactivation and induce ERβ activity. This specific upregulation of ERβ isoform activity of compound 45 may be responsible for the antiosteoporotic activity at picomolar concentration. In addition, both the compounds were also devoid of any estrogenic activity, which correlates to their antiestrogenic behaviour in the two breast cancer cell lines. Assessment of selectivity using specific SiRNAs for ERα and ERβ revealed that most of the compounds showed ERα and ERβ-mediated action, except compound 28, which showed selectivity to ERα only. Computational docking analysis of active compounds 18 and 45 was conducted to correlate the interaction with the two receptors and it was found that the docked conformations of the coumarin prototype, compound 18 at ERα and ERβ active sites were more or less superimposable on each other. However, the unique orientation of the aminoalkoxy side chain of novel chromene (prototype III) compound 45 in the ERβ binding cavity may be responsible for its potential biological response.

  我们合成了几种新的香豆素和色烯原型衍生物，并对它们的ERα和ERβ选择性活性进行了评估。研究发现，香豆素原型化合物 18 和 19 具有ERδ选择性，活性最强，对ER+ve 和 ER âve 乳腺癌细胞系都具有潜在的抗增殖活性。然而，该系列的惊喜发现是新型原型 III 色烯化合物 45 和 46，其第 6 位被酰基取代。这两种化合物对两种乳腺癌细胞系都有很强的抗增殖活性，能促进碱性磷酸酶活性，增强体外成骨细胞矿化，显著降低EREâERα依赖性转录活化并诱导ERβ活性。化合物 45 对ERδ同工酶活性的这种特异性上调可能是其在皮摩尔浓度下具有抗骨质疏松活性的原因。此外，这两种化合物也没有任何雌激素活性，这与它们在两种乳腺癌细胞系中的抗雌激素作用有关。利用特异性 SiRNA 对 ERα 和 ERβ 的选择性进行评估后发现，除化合物 28 仅对 ERα 具有选择性外，大多数化合物都具有 ERα 和 ERβ 介导的作用。对活性化合物 18 和 45 进行了计算对接分析，以确定其与两种受体的相互作用，结果发现香豆素原型化合物 18 在 ERα 和 ERβ 活性位点的对接构象或多或少可以相互叠加。不过，新型香豆素（原型 III）化合物 45 的氨基烷氧基侧链在 ERβ 结合腔中的独特取向可能是其潜在生物反应的原因。
• Synthesis and biological evaluation of trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxyalkylamine derivatives against drug susceptible, non-replicating M. tuberculosis H37Rv and clinical multidrug resistant strains
  作者：Shailesh Kumar、Atma P. Dwivedi、Vivek Kr. Kashyap、A.K. Saxena、A.K. Dwivedi、Ranjana Srivastava、Devi P. Sahu

  DOI：10.1016/j.bmcl.2013.02.030

  日期：2013.4

  Synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of Mycobacterium tuberculosis have been reported. All the new compounds in the series exhibited MIC between 1.56 and 6.25 mu g/ml. Two compounds 1i and 1j with low MIC and low cytotoxicity showed significant reduction in CFU in infected mouse macrophages at 1 x MIC concentration. The compound 1i inhibited the growth of M. tuberculosis in mice at 100 mg/kg dose with 1.35 log(10) reduction of CFU in lungs tissue and was active against non-replicating Mycobacterium tuberculosis under anaerobic condition. (C) 2013 Elsevier Ltd. All rights reserved.
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF TRANS 3,4- DIARYLCHROMAN AND THEIR DERIVATIVES<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE 3,4- DIARYLCHROMANE ET LEURS DÉRIVÉS
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2009078029A3

  公开（公告）日：2009-08-13