(E)-3-(4,5-dimethoxy-2-methoxycarbonylmethylphenyl)but-2-enoic acid methyl ester | 1315171-91-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(4,5-dimethoxy-2-methoxycarbonylmethylphenyl)but-2-enoic acid methyl ester
• 英文别名: methyl (E)-3-[4,5-dimethoxy-2-(2-methoxy-2-oxoethyl)phenyl]but-2-enoate
• CAS: 1315171-91-5
• 化学式: C₁₆H₂₀O₆
• 分子量: 308.331
• InChiKey: RDVZQOMEKQEMBW-UXBLZVDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(4,5-dimethoxy-2-methoxycarbonylmethylphenyl)but-2-enoic acid methyl ester 在 盐酸 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 三溴化硼 、 三乙胺 、 diborane(6) 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， -78.0~125.0 ℃ 、413.7 kPa 条件下， 反应 7.75h， 生成 (+/-)-trans-10,11-dihydroxy-8β-methyl-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine hydrobromide
  参考文献：
  名称：

  Probing the Steric Space at the Floor of the D₁ Dopamine Receptor Orthosteric Binding Domain: 7α-, 7β-, 8α-, and 8β-Methyl Substituted Dihydrexidine Analogues

  摘要：

  To probe the space at the floor of the orthosteric ligand binding site in the dopamine D-1 receptor, four methylated analogues of dihydrexidine (DHX) were synthesized with substitutions at the 7 and 8 positions. The 8 alpha-axial, 8 beta-equatorial, and 7 alpha-equatorial were synthesized by photochemical cyclization of appropriately substituted N-benzoyl enamines, and the 7 beta-axial analogue was prepared by an intramolecular Henry reaction. All of the methylated analogues displayed losses in affinity when compared to DHX (20 nM): 8 beta-Me-ax-DHX (270 nM), 8 alpha-Me-eq-DHX (920 nM), 7 beta-Me-eq-DHX (6540 nM), and 7 alpha-Me-ax-DFLX (>10000 nM). Molecular modeling studies suggest that although the disruption of an aromatic interaction between Phe203(54.7) and Phe288(6.51) is the cause for the 14-fold loss in affinity associated with 8 beta-axial substitution, unfavorable steric interactions with Ser107(3.36) result in the more dramatic decreases in binding affinity suffered by the rest of the analogues.

  DOI：

  10.1021/jm200334c
• 作为产物：
  描述：

  2-(2-碘-4,5-二甲氧基苯基)乙酸 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 96.0h， 生成 (E)-3-(4,5-dimethoxy-2-methoxycarbonylmethylphenyl)but-2-enoic acid methyl ester
  参考文献：
  名称：

  Probing the Steric Space at the Floor of the D₁ Dopamine Receptor Orthosteric Binding Domain: 7α-, 7β-, 8α-, and 8β-Methyl Substituted Dihydrexidine Analogues

  摘要：

  To probe the space at the floor of the orthosteric ligand binding site in the dopamine D-1 receptor, four methylated analogues of dihydrexidine (DHX) were synthesized with substitutions at the 7 and 8 positions. The 8 alpha-axial, 8 beta-equatorial, and 7 alpha-equatorial were synthesized by photochemical cyclization of appropriately substituted N-benzoyl enamines, and the 7 beta-axial analogue was prepared by an intramolecular Henry reaction. All of the methylated analogues displayed losses in affinity when compared to DHX (20 nM): 8 beta-Me-ax-DHX (270 nM), 8 alpha-Me-eq-DHX (920 nM), 7 beta-Me-eq-DHX (6540 nM), and 7 alpha-Me-ax-DFLX (>10000 nM). Molecular modeling studies suggest that although the disruption of an aromatic interaction between Phe203(54.7) and Phe288(6.51) is the cause for the 14-fold loss in affinity associated with 8 beta-axial substitution, unfavorable steric interactions with Ser107(3.36) result in the more dramatic decreases in binding affinity suffered by the rest of the analogues.

  DOI：

  10.1021/jm200334c

文献信息

• Probing the Steric Space at the Floor of the D₁ Dopamine Receptor Orthosteric Binding Domain: 7α-, 7β-, 8α-, and 8β-Methyl Substituted Dihydrexidine Analogues
  作者：Juan Pablo Cueva、Alejandra Gallardo-Godoy、Jose I. Juncosa、Pierre A. Vidi、Markus A. Lill、Val J. Watts、David E. Nichols

  DOI：10.1021/jm200334c

  日期：2011.8.11

  To probe the space at the floor of the orthosteric ligand binding site in the dopamine D-1 receptor, four methylated analogues of dihydrexidine (DHX) were synthesized with substitutions at the 7 and 8 positions. The 8 alpha-axial, 8 beta-equatorial, and 7 alpha-equatorial were synthesized by photochemical cyclization of appropriately substituted N-benzoyl enamines, and the 7 beta-axial analogue was prepared by an intramolecular Henry reaction. All of the methylated analogues displayed losses in affinity when compared to DHX (20 nM): 8 beta-Me-ax-DHX (270 nM), 8 alpha-Me-eq-DHX (920 nM), 7 beta-Me-eq-DHX (6540 nM), and 7 alpha-Me-ax-DFLX (>10000 nM). Molecular modeling studies suggest that although the disruption of an aromatic interaction between Phe203(54.7) and Phe288(6.51) is the cause for the 14-fold loss in affinity associated with 8 beta-axial substitution, unfavorable steric interactions with Ser107(3.36) result in the more dramatic decreases in binding affinity suffered by the rest of the analogues.