N-methyl-N-<(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl>-3-nitrophenylacetamide | 116508-31-7

• 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-nitrophenylacetamide
• 英文别名: 2-(3-Nitrophenyl)-N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]acetamide；N-Methyl-2-(3-nitro-phenyl)-N-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl)-acetamide；N-methyl-2-(3-nitrophenyl)-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide
• CAS: 116508-31-7
• 化学式: C₂₁H₂₅N₃O₃
• 分子量: 367.448
• InChiKey: BETSPOMRBAOPQA-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methyl-N-<(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl>-3-nitrophenylacetamide 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以78%的产率得到N-methyl-N-<(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl>-3-aminophenylacetamide
  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
• 作为产物：
  描述：

  3-硝基苯乙酸 、 (S)-N-methyl-1-phenyl-2-(pyrrolidin-1-yl)ethanamine 在 吡啶 、 N,N'-二环己基碳二亚胺 作用下， 生成 N-methyl-N-<(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl>-3-nitrophenylacetamide
  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

• Kappa agonist compounds and pharmaceutical formulations thereof
  申请人：——

  公开号：US20030144272A1

  公开（公告）日：2003-07-31

  Compounds having kappa opioid agonist activity, compositions containing them and method of using them as analgesics are provided. The compounds of formulae I, II, IIA, III, IIIA, IIIB, IIIB-i, IV and IVA have the structure: 1 2 wherein R 1 , R 2 , R 3 , R 4 ; and X, X 4 , X 5 , X 7 , X 9 ; Y, Z and n are as described in the specification.

  提供具有kappa阿片受体激动剂活性的化合物，含有这些化合物的组合物以及使用它们作为镇痛剂的方法。 具有以下结构的化合物I、II、IIA、III、IIIA、IIIB、IIIB-i、IV和IVA： 1 2 其中 R 1 ，R 2 ，R 3 ，R 4 ；和 X，X 4 ，X 5 ，X 7 ，X 9 ； Y，Z和n如规范中所述。
• Kappa agonist compounds, pharmaceutical formulations and method of prevention and treatment of pruritus therewith
  申请人：——

  公开号：US20040220112A1

  公开（公告）日：2004-11-04

  Compounds having kappa opioid agonist activity, compositions containing them and method of using them as analgesics and pruritic agents are provided. The compounds of formulae I, II, III and IV have the structure: 1 wherein X, X 4 , X 5 , X 7 , X 9 ; R 1 , R 2 , R 3 , R 4 ; and Y, Z and n are as described in the specification

  提供具有kappa阿片受体激动剂活性的化合物、包含它们的组合物和使用它们作为镇痛剂和止痒剂的方法。公式I、II、III和IV的化合物具有以下结构：1其中X、X4、X5、X7、X9；R1、R2、R3、R4；以及Y、Z和n的描述如规范中所述。
• 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：——
• KAPPA AGONIST COMPOUNDS, PHARMACEUTICAL FORMULATIONS AND METHOD OF PREVENTION AND TREATMENT OF PRURITUS THEREWITH
  申请人：Adolor Corporation

  公开号：EP0998281A1

  公开（公告）日：2000-05-10
• JP2001510154A
  申请人：——

  公开号：JP2001510154A

  公开（公告）日：2001-07-31