3-(3,4-dimethoxyphenyl)propanoic acid sodium salt

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-(3,4-dimethoxyphenyl)propanoic acid sodium salt
• 英文别名: Sodium;3-(3,4-dimethoxyphenyl)propanoate
• 化学式: C₁₁H₁₃O₄*Na
• 分子量: 232.212
• InChiKey: ZYKSSUHAAAXDBC-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.61
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3,4-dimethoxyphenyl)propanoic acid sodium salt 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-(3,4-dimethoxy-phenyl)-propionyl chloride
  参考文献：
  名称：

  Dopamine D₃ Receptor Antagonists. 1. Synthesis and Structure−Activity Relationships of 5,6-Dimethoxy-N-alkyl- and N-Alkylaryl-Substituted 2-Aminoindans

  摘要：

  5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D-3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D-3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D-3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D-3 binding affinity, the D-2 affinity is also enhanced, resulting in a less than 4-fold preference for the D-3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D-3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3. Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (similar to 65%) from the indanone 5c.

  DOI：

  10.1021/jm010145w

文献信息

• Method of inhibiting sweetness
  申请人：TATE & LYLE PUBLIC LIMITED COMPANY

  公开号：EP0125049A1

  公开（公告）日：1984-11-14

  The sweetness of an ingestible product containing a sweetening sugar or sugar alcohol in large quantities can be reduced by incorporating therein a sweetness-reducing amount of at least one compound of the general formula: in which m represents 0 or 1, and when m represents 0, n represents 1, 2 or 3, and p represents 1,2.3 or 4, and when m represents 1, n represents 1 or 2 and p represents 0,1,2,3 or 4; the substituents R, which may be the same or different, each represent a lower alkoxy group, e.g. with 1 to 5 carbon atoms, phenoxy group or a lower alkyl or trifluoromethyl group; and/or two substituents R together represent an aliphatic chain linked to the phenyl ring at two positions, either directly or via an oxa-group, e.g. an alkylenedioxy, alkenylenedioxy, alkylenoxy or alkenylenoxy group; and/or one substituent R represents a hydroxy group while at least one other substituent R represents an alkoxy group; and X+represents a physiologically acceptable cation.

  在含有大量甜味剂糖或糖醇的可食用产品中加入至少一种通式如下的化合物，可降低其甜度： 其中 m 代表 0 或 1，当 m 代表 0 时，n 代表 1、2 或 3，p 代表 1、2.3 或 4，当 m 代表 1 时，n 代表 1 或 2，p 代表 0、1、2、3 或 4；取代基 R 可以相同或不同，各自代表一个低级烷氧基，例如当 m 代表 1、n 代表 1 或 2，p 代表 0、1、2、3 或 4 时；取代基 R 可以相同或不同，各自代表低级烷氧基，如 1 至 5 个碳原子的低级烷氧基、苯氧基或低级烷基或三氟甲基；和/或两个取代基 R 共同代表在两个位置上与苯基环相连的脂肪族链，可以是直接相连的，也可以是通过氧代基相连的，如烷二氧基、烯二氧基、烷氧基或烯氧基；和/或一个取代基 R 代表羟基，而至少另一个取代基 R 代表烷氧基；X+ 代表生理上可接受的阳离子。
• US4567053A
  申请人：——

  公开号：US4567053A

  公开（公告）日：1986-01-28
• Dopamine D₃ Receptor Antagonists. 1. Synthesis and Structure−Activity Relationships of 5,6-Dimethoxy-<i>N</i>-alkyl- and <i>N</i>-Alkylaryl-Substituted 2-Aminoindans
  作者：Susanne R. Haadsma-Svensson、Kerry A. Cleek、Dac M. Dinh、J. Neil Duncan、Christopher L. Haber、Rita M. Huff、Mary E. Lajiness、Nanette F. Nichols、Martin W. Smith、Kjell A. Svensson、Matt J. Zaya、Arvid Carlsson、Chiu-Hong Lin

  DOI：10.1021/jm010145w

  日期：2001.12.1

  5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D-3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D-3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D-3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D-3 binding affinity, the D-2 affinity is also enhanced, resulting in a less than 4-fold preference for the D-3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D-3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3. Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (similar to 65%) from the indanone 5c.