4-[(E)-N-hydroxy-C-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)carbonimidoyl]benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 4-[(E)-N-hydroxy-C-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)carbonimidoyl]benzoic acid
• 化学式: C₂₃H₂₇NO₃
• 分子量: 365.472
• InChiKey: ZDSBRLPUWAHPHO-HIXSDJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  69.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,5-二氯-2,5-二甲基己烷 在 sodium hydroxide 、 三氯化铝 、 羟胺 、 三氯化铁 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 反应 19.0h， 生成 4-[(E)-N-hydroxy-C-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)carbonimidoyl]benzoic acid
  参考文献：
  名称：

  新的类维生素A X受体选择性类维生素A的合成。

  摘要：

  类维生素A 1-5已被确定为有效的RXR激动剂，可用于治疗非胰岛素依赖型（II型）糖尿病（NIDDM）。已经开发了1-5的高度收敛的合成。使用AlCl（3）催化（0.03当量）甲苯与2,5-二氯-2,5-二甲基己烷的Friedel-Crafts烷基化反应以98％的产率制备用于1和2合成的核心四氢萘7 6.开发了用氯甲基烟酸酯9的硝基甲烷介导的Fridel-Crafts 7的酰化反应，以68％的产率制备酮10。将螯合剂控制的MeMgCl加入10中，然后进行脱水，以65％的收率得到烯烃11。用三甲基磺酸ox叶立德对11进行环丙烷化，然后进行皂化，完成了1的五步合成，产率为33％。FeCl（3）催化（0。05当量）用对苯二甲酸氯甲酯14对7进行Friedel-Crafts酰化，得到酮15，产率为81％。皂化15并与50％NH（2）OH在AcOH中的水溶液反应，得到顺式和反式肟的9：1混合物，从其

  DOI：

  10.1021/jo0103064

文献信息

• Synthesis of Retinoid X Receptor-Specific Ligands That Are Potent Inducers of Adipogenesis in 3T3-L1 Cells
  作者：Stacie S. Canan Koch、Laura J. Dardashti、Rosemary M. Cesario、Glenn E. Croston、Marcus F. Boehm、Richard A. Heyman、Alex M. Nadzan

  DOI：10.1021/jm980621r

  日期：1999.2.1

  A novel series of oxime ligands has been synthesized that displays potent, specific activation of the retinoid X receptors (RXRs). The oximes of S-substituted (tetramethyltetrahydronaphthyl)carbonylbenzoic acids are readily available by condensation with hydroxyl- or methoxylamine; alkylation of the hydroxyl oxime provides a variety of analogues. Grimes and variously substituted oxime derivatives demonstrate high binding affinity for the RXRs and specific RXR activation and, hence, are called rexinoids. These oxime rexinoids are activators of the RXR: PPAR gamma heterodimer and are potent inducers of differentiation of 3T3-L1 preadipocytes to adipocytes. We have recently reported that ligands which activate the RXR:PPAR gamma heterodimer in this manner are effective in the treatment of type II diabetes (non-insulin-dependent diabetes mellitus, NIDDM). Thus, these new oxime rexinoids are potential therapeutic agents for the treatment of metabolic disorders, such as obesity and diabetes.
• Methods and pharmaceutical compositions for treatment of anti-estrogen resistant breast cancer using RXR modulators
  申请人：Lamph W. William

  公开号：US20070238791A1

  公开（公告）日：2007-10-11

  Methods and compositions for the treatment of anti-estrogen resistant breast cancer using retinoid compounds that are modulators of Retinoid X Receptors are provided.
• Method and Pharmaceutical Compositions for Treatment of Anti-Estrogen Resistant Breast Cancer Using RXR Modulators
  申请人：Lamph William W.

  公开号：US20090093546A1

  公开（公告）日：2009-04-09

  Methods and compositions for the treatment of anti-estrogen resistant breast cancer using retinoid compounds that are modulators of Retinoid X Receptors are provide.
• RXR AGONIST COMPOUNDS AND METHODS
  申请人：Landreth Gary E.

  公开号：US20120115912A1

  公开（公告）日：2012-05-10

  A method of treating a PPARγ and/or RXR related disease or disorder in a subject includes adminstering to the subject an RXR agonist alone or in combination with a PPARγ agonist.
• US7259188B2
  申请人：——

  公开号：US7259188B2

  公开（公告）日：2007-08-21