N-methyl-N-<(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl>-3-isothiocyanatophenylacetamide

• 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: N-methyl-N-<(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl>-3-isothiocyanatophenylacetamide
• 英文别名: 2-(3-Isothiocyanato-phenyl)-N-methyl-N-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl)-acetamide；2-(3-isothiocyanatophenyl)-N-methyl-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide
• 化学式: C₂₂H₂₅N₃OS
• 分子量: 379.526
• InChiKey: AQNKJLVANZELEX-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  68
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-硝基苯乙酸 在 palladium on activated charcoal 吡啶 、 盐酸 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 32.03h， 生成 N-methyl-N-<(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl>-3-isothiocyanatophenylacetamide
  参考文献：
  名称：

  Isothiocyanate-Substituted .kappa.-Selective Opioid Receptor Ligands Derived from N-Methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]phenylacetamide

  摘要：

  The synthesis of isothiocyanate-substituted K-selective opioid ligands derived from N-methyl-N-[(1S)-1-phenyl-2- (1-pyrrolidinyl)ethyl]ethyl]phenylacetamide (8) and their effects in radioligand displacement assays are reported. Ligands 3-5 with the S-absolute configuration were prepared with the isothiocyanate functionality at the 2-, 3-, and 4-positions in the phenylacetamide aromatic ring. The 2-isothiocyanato-4,5-dichlorophenylacetamide 6 was prepared to evaluate the effect of 4,5-dichloro substitution in the same aromatic ring as the 2-isothiocyanate function. N-Methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]-3,4-dichlorophenylacetamide (7), with the 4-isothiocyanate function in the 1-phenyl ring, was prepared for comparison with the other compounds in the series. Of the prepared ligands, 7 and 8 (IC(50)s similar or equal to 1.4-1.8 nM) were approximately equal in affinity with 2 (ICI-199,441), followed by 3 and 6. All of these compounds were more kappa-selective than 2, as well. The binding characteristics of 8 show that the previously reported 4,5-dichloro substitution is not required for high affinity and kappa-selectivity. All of the synthesized isothiocyanate-substituted ligands irreversibly inhibited radioligand binding to guinea pig brain membrane preparations, including compound 2 (ICI-199,441) which had no isothiocyanate functionality.

  DOI：

  10.1021/jm00044a006

文献信息

• Weerawarna S. Ananda, Davis Ronda D., Nelson Wendel L., J. Med. Chem, 37 (1994) N 18, S 2856-2864
  作者：Weerawarna S. Ananda, Davis Ronda D., Nelson Wendel L.

  DOI：——

  日期：——
• Isothiocyanate-Substituted .kappa.-Selective Opioid Receptor Ligands Derived from N-Methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]phenylacetamide
  作者：S. Ananda Weerawarna、Ronda D. Davis、Wendel L. Nelson

  DOI：10.1021/jm00044a006

  日期：1994.9

  The synthesis of isothiocyanate-substituted K-selective opioid ligands derived from N-methyl-N-[(1S)-1-phenyl-2- (1-pyrrolidinyl)ethyl]ethyl]phenylacetamide (8) and their effects in radioligand displacement assays are reported. Ligands 3-5 with the S-absolute configuration were prepared with the isothiocyanate functionality at the 2-, 3-, and 4-positions in the phenylacetamide aromatic ring. The 2-isothiocyanato-4,5-dichlorophenylacetamide 6 was prepared to evaluate the effect of 4,5-dichloro substitution in the same aromatic ring as the 2-isothiocyanate function. N-Methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]-3,4-dichlorophenylacetamide (7), with the 4-isothiocyanate function in the 1-phenyl ring, was prepared for comparison with the other compounds in the series. Of the prepared ligands, 7 and 8 (IC(50)s similar or equal to 1.4-1.8 nM) were approximately equal in affinity with 2 (ICI-199,441), followed by 3 and 6. All of these compounds were more kappa-selective than 2, as well. The binding characteristics of 8 show that the previously reported 4,5-dichloro substitution is not required for high affinity and kappa-selectivity. All of the synthesized isothiocyanate-substituted ligands irreversibly inhibited radioligand binding to guinea pig brain membrane preparations, including compound 2 (ICI-199,441) which had no isothiocyanate functionality.