4-(2',3'-dimethoxyphenyl)-3-butenoic acid | 81580-84-9

• 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: 4-(2',3'-dimethoxyphenyl)-3-butenoic acid
• 英文别名: 4-(2,3-dimethoxyphenyl)but-3-enoic acid
• CAS: 81580-84-9
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: GCYOJJMTMPZVLH-UHFFFAOYSA-N

物化性质

• 熔点：
  84-86 °C
• 沸点：
  382.8±32.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2',3'-dimethoxyphenyl)-3-butenoic acid 在 ammonium hydroxide 、 PPA 、 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 作用下， 以 甲醇 、 乙醇 、 甲苯 为溶剂， 20.0~60.0 ℃ 、405.33 kPa 条件下， 反应 21.5h， 生成 (5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methanamine hydrochloride
  参考文献：
  名称：

  绘制多巴胺 D1 受体中的儿茶酚结合位点：两个平行系列的双环多巴胺类似物的合成和评价

  摘要：

  最初由雅培实验室报道的一类新型异色满多巴胺类似物对 D 1样受体的选择性比 D 2样受体高100 倍以上。我们合成了一系列平行的色满化合物，并表明在杂环中重新定位氧原子会降低效力并赋予这些化合物D 2样受体选择性。计算机模拟支持以下假设：色满系列的药理学改变是由于色满环中的氧和间位之间潜在的分子内氢键-邻苯二酚部分的羟基。这种相互作用重新排列了儿茶酚羟基并破坏了这些配体与 D 1样受体的TM5 中关键丝氨酸残基之间的关键相互作用。这一假设通过一系列平行碳环化合物的合成和药理学评价进行了测试。我们的结果表明，如果去除分子内氢键的潜力，D 1样受体效力和选择性就会恢复。

  DOI：

  10.1002/cmdc.201100010
• 作为产物：
  描述：

  2-(2,3-dimethoxyphenyl)-5-oxo-tetrahydrofuran-3-carboxylic acid 反应 12.0h， 以65%的产率得到4-(2',3'-dimethoxyphenyl)-3-butenoic acid
  参考文献：
  名称：

  八氢苯并[h]异喹啉的简便合成：新型高效D1多巴胺激动剂

  摘要：

  八氢苯并[ h ]异喹啉支架作为一种构象受限的苯乙胺，可用于构建生物活性产品。然而，令人惊讶的是，没有报道该环系统的易处理合成。我们现在描述一种获得该框架的简便方法，并说明我们的方法很容易适用于 5 位替换。重要的是，我们证明了 7,8-二羟基-5-苯基取代的配体是一种极其有效、高亲和力、全 D 1多巴胺受体选择性激动剂。

  DOI：

  10.1016/j.bmc.2010.07.052

文献信息

• Facile synthesis of octahydrobenzo[h]isoquinolines: Novel and highly potent D1 dopamine agonists
  作者：Lisa A. Bonner、Benjamin R. Chemel、Val J. Watts、David E. Nichols

  DOI：10.1016/j.bmc.2010.07.052

  日期：2010.9

  scaffold is of interest as a conformationally-restricted phenethylamine that may be useful for constructing biologically active products. Surprisingly, however, no tractable synthesis of this ring system has been reported. We now describe a facile method for obtaining this framework, and illustrate that our approach is easily amenable to substitutions at the 5-position. Importantly, we demonstrate that

  八氢苯并[ h ]异喹啉支架作为一种构象受限的苯乙胺，可用于构建生物活性产品。然而，令人惊讶的是，没有报道该环系统的易处理合成。我们现在描述一种获得该框架的简便方法，并说明我们的方法很容易适用于 5 位替换。重要的是，我们证明了 7,8-二羟基-5-苯基取代的配体是一种极其有效、高亲和力、全 D 1多巴胺受体选择性激动剂。
• [EN] OCTAHYDROBENZOISOQUINOLINE MODULATORS OF DOPAMINE RECEPTORS AND USES THEREFOR<br/>[FR] MODULATEURS OCTAHYDROBENZOISOQUINOLÉINES DE RÉCEPTEURS DE LA DOPAMINE, ET UTILISATIONS DE CES MODULATEURS
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2010124005A1

  公开（公告）日：2010-10-28

  Octahydrobenzoisoquinoline modulators of dopamine receptors are described herein. Methods for using octahydrobenzoisoquinoline modulators of dopamine receptors in the treatment of dopamine dysfunction are also described herein.

  本文描述了对多巴胺受体进行调节的八氢苯并异喹啉。本文还描述了使用八氢苯并异喹啉调节多巴胺受体治疗多巴胺功能障碍的方法。
• OCTAHYDROBENZOISOQUINOLINE MODULATORS OF DOPAMINE RECEPTORS AND USES THEREFOR
  申请人：Nichols David E.

  公开号：US20120041018A1

  公开（公告）日：2012-02-16

  Octahydrobenzoisoquinoline modulators of dopamine receptors are described herein. Methods for using octahydrobenzoisoquinoline modulators of dopamine receptors in the treatment of dopamine dysfunction are also described herein.

  本文描述了八氢苯并异喹啉多巴胺受体调节剂。本文还描述了使用八氢苯并异喹啉多巴胺受体调节剂治疗多巴胺功能障碍的方法。
• Octahydrobenzoisoquinoline modulators of dopamine receptors and uses therefor
  申请人：Nichols David E.

  公开号：US09359303B2

  公开（公告）日：2016-06-07

  Octahydrobenzoisoquinoline modulators of dopamine receptors are described herein. Methods for using octahydrobenzoisoquinoline modulators of dopamine receptors in the treatment of dopamine dysfunction are also described herein.

  本文描述了八氢苯并异喹啉多巴胺受体调节剂。本文还描述了使用八氢苯并异喹啉多巴胺受体调节剂治疗多巴胺功能障碍的方法。
• Synthesis and Reactivity of the Catechol Metabolites from the Equine Estrogen, 8,9-Dehydroestrone
  作者：Fagen Zhang、Dan Yao、Yousheng Hua、Richard B. van Breemen、Judy L. Bolton

  DOI：10.1021/tx010049y

  日期：2001.6.1

  The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with an increased cancer risk. Previously, we showed that the equine estrogens equilin and equilenin, which are major components of the widely prescribed estrogen replacement formulation Premarin, are metabolized to highly cytotoxic quinoids which caused oxidative stress and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. Chem. Res. Toxicol. 1998, 11, 1113-1127]. In this study, we have synthesized 8,9-dehydroestrone (a third equine estrogen component of Premarin) and its potential catechol metabolites, 4-hydroxy-8,9-dehydroestrone and 2-hydroxy-8,9-dehydroestrone. Both 2-hydroxy-8,9-dehydroestrone and 4-hydroxy-8,9-dehydroestrone were oxidized by tyrosinase or rat liver microsomes to o-quinones which reacted with GSH to give one mono-GSH conjugate and two di-GSH conjugates. Like endogenous estrogens, 8,9-dehydroestrone was primarily converted by rat liver microsomes to the 2-hydroxylated rather than the 4-hydroxylated o-quinone GSH conjugates; the ratio of 2-hydroxy-8,9-dehydroestrone versus 4-hydroxy-8,9-dehydroestrone was 6:1. Also in contrast to experiments with equilin, 4-hydroxyequilenin was not observed in microsomal incubations with 8,9-dehydroestrone or its catechols. The behavior of 2-hydroxy-8,9-dehydroestrone was found to be more complex than 4-hydroxy-8,9-dehydroestrone as GSH conjugates resulting from 2-hydroxy-8,9-dehydroestrone were detected even without oxidative enzyme catalysis. Under physiological conditions, 2-hydroxy-8,9-dehydroestrone isomerized to 8-hydroxyequilenin to form the very stable 2-hydroxyequilenin catechol; however, 4-hydroxy-8,9-dehydroestrone was found to be stable under similar conditions. Finally, preliminary studies conducted with the human breast tumor S-30 cell lines demonstrated that the catechol metabolites of 8,9-dehydroestrone were much less toxic than 4-hydroxyequilenin (20-40-fold). These results suggest that the catechol metabolites of 8,9-dehydroestrone may have the ability to cause cytotoxicity in vivo primarily through formation of o-quinones; however, most of the adverse effects of Premarin estrogens are likely due to formation of 4-hydroxyequilenin o-quinone from equilin and equilenin.