(R,S)-2-cyano-3-(4-hydroxy-2',6'-dimethylphenyl)-propanoic acid ethyl ester | 254102-29-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (R,S)-2-cyano-3-(4-hydroxy-2',6'-dimethylphenyl)-propanoic acid ethyl ester
• 英文别名: Ethyl 2-cyano-3-(4-hydroxy-2,6-dimethylphenyl)propanoate
• CAS: 254102-29-9
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: XCXSCWIDHSIAGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R,S)-2-cyano-3-(4-hydroxy-2',6'-dimethylphenyl)-propanoic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 以85%的产率得到(R,S)-2-cyano-3-(4-hydroxy-2',6'-dimethylphenyl)-propanoic acid
  参考文献：
  名称：

  Further Studies on the Dmt-Tic Pharmacophore:  Hydrophobic Substituents at the C-Terminus Endow δ Antagonists To Manifest μ Agonism or μ Antagonism

  摘要：

  Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K-i values with either [H-3]DPDPE (delta(1) agonist) or [H-3]N,N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH2, -NHCH3, -NH-1-adamantyl, -NH-tBu, -NH-5-tetrazolyl) had high delta affinities (K-i = 0.16 to 1 nM) with variable mu affinities to yield nonselective or weakly mu-selective analogues, N,N-(Me)(2)Dmt-Tic-NH-1-adamantane exhibited dual delta and mu receptor affinities (K(i)delta = 0.16 nM and K(i)mu =1.12 nM) and potent delta antagonism (pA(2) = 9.06) with mu agonism (IC50 = 16 nM). H-Dmt-beta HTic-OH (methylene bridge between C-alpha of Tic and carboxylate function) yielded a biostable peptide with high delta affinity (K-i = 0.85 nM) and delta antagonism (pA(2) = 8.85) without mu bioactivity, Dmt-Tic-Ala-X (X = -NHCH3, -OCH3, -NH-1-adamantyl, -NHtBu) exhibited high delta affinities (K-i = 0.06 to 0.2 nM) and elevated mu affinities (K-i = 2.5 to 11 nM), but only -Dmt-Tic-Ala-NH-1-adamantane and H-Dmt-Tic-Ala-NHtBu yielded delta receptor antagonism (pA(2) = 9.29 and 9.16, respectively). Thus, Dmt-Tic with hydrophobic C-terminal substituents enhanced mu affinity to provide delta antagonists with dual receptor affinities and bifunctional activity.

  DOI：

  10.1021/jm990165m
• 作为产物：
  描述：

  [4-(氯甲基)-3,5-二甲基苯基]碳酸乙酯 、 氰乙酸乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以60%的产率得到(R,S)-2-cyano-3-(4-hydroxy-2',6'-dimethylphenyl)-propanoic acid ethyl ester
  参考文献：
  名称：

  Further Studies on the Dmt-Tic Pharmacophore:  Hydrophobic Substituents at the C-Terminus Endow δ Antagonists To Manifest μ Agonism or μ Antagonism

  摘要：

  Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K-i values with either [H-3]DPDPE (delta(1) agonist) or [H-3]N,N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH2, -NHCH3, -NH-1-adamantyl, -NH-tBu, -NH-5-tetrazolyl) had high delta affinities (K-i = 0.16 to 1 nM) with variable mu affinities to yield nonselective or weakly mu-selective analogues, N,N-(Me)(2)Dmt-Tic-NH-1-adamantane exhibited dual delta and mu receptor affinities (K(i)delta = 0.16 nM and K(i)mu =1.12 nM) and potent delta antagonism (pA(2) = 9.06) with mu agonism (IC50 = 16 nM). H-Dmt-beta HTic-OH (methylene bridge between C-alpha of Tic and carboxylate function) yielded a biostable peptide with high delta affinity (K-i = 0.85 nM) and delta antagonism (pA(2) = 8.85) without mu bioactivity, Dmt-Tic-Ala-X (X = -NHCH3, -OCH3, -NH-1-adamantyl, -NHtBu) exhibited high delta affinities (K-i = 0.06 to 0.2 nM) and elevated mu affinities (K-i = 2.5 to 11 nM), but only -Dmt-Tic-Ala-NH-1-adamantane and H-Dmt-Tic-Ala-NHtBu yielded delta receptor antagonism (pA(2) = 9.29 and 9.16, respectively). Thus, Dmt-Tic with hydrophobic C-terminal substituents enhanced mu affinity to provide delta antagonists with dual receptor affinities and bifunctional activity.

  DOI：

  10.1021/jm990165m

文献信息

• Further Studies on the Dmt-Tic Pharmacophore:  Hydrophobic Substituents at the C-Terminus Endow δ Antagonists To Manifest μ Agonism or μ Antagonism
  作者：Severo Salvadori、Remo Guerrini、Gianfranco Balboni、Clementina Bianchi、Sharon D. Bryant、Peter S. Cooper、Lawrence H. Lazarus

  DOI：10.1021/jm990165m

  日期：1999.12.2

  Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K-i values with either [H-3]DPDPE (delta(1) agonist) or [H-3]N,N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH2, -NHCH3, -NH-1-adamantyl, -NH-tBu, -NH-5-tetrazolyl) had high delta affinities (K-i = 0.16 to 1 nM) with variable mu affinities to yield nonselective or weakly mu-selective analogues, N,N-(Me)(2)Dmt-Tic-NH-1-adamantane exhibited dual delta and mu receptor affinities (K(i)delta = 0.16 nM and K(i)mu =1.12 nM) and potent delta antagonism (pA(2) = 9.06) with mu agonism (IC50 = 16 nM). H-Dmt-beta HTic-OH (methylene bridge between C-alpha of Tic and carboxylate function) yielded a biostable peptide with high delta affinity (K-i = 0.85 nM) and delta antagonism (pA(2) = 8.85) without mu bioactivity, Dmt-Tic-Ala-X (X = -NHCH3, -OCH3, -NH-1-adamantyl, -NHtBu) exhibited high delta affinities (K-i = 0.06 to 0.2 nM) and elevated mu affinities (K-i = 2.5 to 11 nM), but only -Dmt-Tic-Ala-NH-1-adamantane and H-Dmt-Tic-Ala-NHtBu yielded delta receptor antagonism (pA(2) = 9.29 and 9.16, respectively). Thus, Dmt-Tic with hydrophobic C-terminal substituents enhanced mu affinity to provide delta antagonists with dual receptor affinities and bifunctional activity.