8-bromo-6-methoxy-2-methyl-chroman-2-carboxylic acid ethyl ester | 936112-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-bromo-6-methoxy-2-methyl-chroman-2-carboxylic acid ethyl ester
• 英文别名: ethyl 8-bromo-6-methoxy-2-methyl-3,4-dihydrochromene-2-carboxylate
• CAS: 936112-89-9
• 化学式: C₁₄H₁₇BrO₄
• 分子量: 329.191
• InChiKey: SGAFBDLVLLDZJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-bromo-6-methoxy-2-methyl-chroman-2-carboxylic acid ethyl ester 在 红铝 作用下， 以 四氢呋喃 为溶剂， 生成 8-bromo-6-methoxy-2-methyl-chroman-2-methanol
  参考文献：
  名称：

  Exploitation of the Ability of γ-Tocopherol to Facilitate Membrane Co-localization of Akt and PHLPP1 to Develop PHLPP1-Targeted Akt Inhibitors

  摘要：

  Previously, we reported that Akt inactivation by gamma-tocopherol (2) in PTEN-negative prostate cancer cells resulted from its unique ability to facilitate membrane co-localization of Akt and PHLPP1 (PH domain leucine-rich repeat protein phosphatase isoform 1), a Ser473-specific Akt phosphatase, through pleckstrin homology (PH) domain binding. This finding provided a basis for exploiting 2 to develop a novel class of PHLPP1-targeted Akt inhibitors. Here, we used 3 (gamma-VE5), a side chain-truncated 2 derivative, as a scaffold for lead optimization. The proof-of-concept of this structural optimization was obtained by 20, which exhibited higher antitumor efficacy than 3 in PTEN-negative cancer cells through PHLPP1-facilitated Akt inactivation. Like 3, 20 preferentially recognized the PH domains of Akt and PHLPP1, as its binding affinities for other PH domains, including those of ILK and PDK1, were an order-of-magnitude lower. Moreover, 20 was orally active in suppressing xenograft tumor growth in nude mice, which underlines the translational potential of this new class of Akt inhibitor in PTEN-deficient cancers.

  DOI：

  10.1021/jm501751b
• 作为产物：
  描述：

  2-溴-4-甲氧基苯酚 、 甲基丙烯酸乙酯 在 聚合甲醛 、 二正丁胺 、 溶剂黄146 作用下， 反应 44.0h， 以42%的产率得到8-bromo-6-methoxy-2-methyl-chroman-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  WO2007/53094

  摘要：

  公开号：

文献信息

• Chroman compounds
  申请人：Bernstein Peter

  公开号：US20070135442A1

  公开（公告）日：2007-06-14

  Compounds according to Formula (I) below: wherein R 1 , R 2 , R 3 , and R 4 are as defined in the specification, pharmaceutically-acceptable salts, methods of making, pharmaceutical compositions containing and methods for using the same.

  根据下面的公式（I）合成化合物： 其中R1、R2、R3和R4如规范中定义，药学上可接受的盐，制备方法，含有该化合物的制药组合物以及使用该化合物的方法。
• [EN] CHROMAN COMPOUNDS AS 5 -HTlB ANTAGONISTS<br/>[FR] COMPOSES CHROMANE UTILISES EN TANT QU'ANTAGONISTES DES 5-HT1B
  申请人：ASTRAZENECA AB

  公开号：WO2007053094A1

  公开（公告）日：2007-05-10

  [EN] Chroman derivatives according to Formula (I) below: wherein R¹, R², R³ ,and R⁴ are as defined in the specification, pharmaceutically-acceptable salts, methods of making, pharmaceutical .compositions containing and methods for using the'' same. The compounds are 5-HT_1B antagonists and are useful in the treatment of mood and . anxiety disorders as well as cognitive disorders.
  [FR] L'invention concerne des dérivés de chromane de formule (I) dans laquelle R¹, R², R³, et R⁴ sont tels que définis dans la description, des sels pharmaceutiquement acceptables de ces dérivés, des procédés de production correspondants, des compositions pharmaceutiques les contenant, ainsi que des procédés d'utilisation desdits composés. Ces composés sont des antagonistes des 5-HT_1B et peuvent servir à traiter les troubles de l'humeur et les troubles anxieux, ainsi que les troubles cognitifs.