N-Boc-N'-(2-nitrophenyl)thiourea | 212701-26-3

• 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-Boc-N'-(2-nitrophenyl)thiourea
• 英文别名: tert-butyl N-[(2-nitrophenyl)carbamothioyl]carbamate
• CAS: 212701-26-3
• 化学式: C₁₂H₁₅N₃O₄S
• 分子量: 297.335
• InChiKey: VTKRMUZLPKBULZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-Boc-N'-(2-nitrophenyl)thiourea 在 三乙胺 、 三氟乙酸 、 mercury dichloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 (S)-1-[N-(2-Nitro-phenyl)-carbamimidoyl]-pyrrolidine-2-carboxylic acid [(S)-1-(benzyl-methyl-carbamoyl)-2-naphthalen-2-yl-ethyl]-amide
  参考文献：
  名称：

  2-Nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N- methylamide (SDZ NKT 343), a Potent Human NK₁ Tachykinin Receptor Antagonist with Good Oral Analgesic Activity in Chronic Pain Models

  摘要：

  A lead compound which had sub-micromolar affinity for the rabbit NK1 receptor but negligible affinity for rat NK1 receptors, 3a, was discovered by directed screening. 2-Substitution in the ring of the benzylthiourea substituent in the initial lead was found to be important, and halogens (Cl, Br) in this position were found to improve affinity for the human receptor. The activity of a series of 2-halo-substituted benzylthioureas was then optimized by modification of the proline diphenylmethyl amide, guided by a simple conceptual model based on structural overlay between these early antagonists and NK1 selective peptides. In this way, aromatic amino acid amides were identified which had improved affinity with respect to the starting diphenylmethyl (DPM) amides. The first sub-nanomolar ligand for the human NK1 receptor which arose from this series, 4af, combined a 2-chlorobenzylthiourea unit with a 2-naphthylalanine amide. Contemporaneously it was discovered that the benzylthiourea unit could be simplified to a phenylthiourea providing that an appropriate 2-substituent was also incorporated. Combination of these two series gave 2-NO2 phenylthiourea analogues which led directly to the analogous urea, 5f(2-nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide, SDZ NKT 343), a highly potent ligand for the human NK1 receptor (K-i = 0.16 nM). In addition to its high in vitro potency, 5f proved to be a potent orally active analgesic in guinea pig models of chronic inflammatory and neuropathic pain. The nature of the 2-aryl substituent was found to be critical for oral activity in this series. Clinical evaluation of 5f as a novel analgesic agent is currently underway.

  DOI：

  10.1021/jm970499g
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 2-硝基苯基硫脲 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以38%的产率得到N-Boc-N'-(2-nitrophenyl)thiourea
  参考文献：
  名称：

  2-Nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N- methylamide (SDZ NKT 343), a Potent Human NK₁ Tachykinin Receptor Antagonist with Good Oral Analgesic Activity in Chronic Pain Models

  摘要：

  A lead compound which had sub-micromolar affinity for the rabbit NK1 receptor but negligible affinity for rat NK1 receptors, 3a, was discovered by directed screening. 2-Substitution in the ring of the benzylthiourea substituent in the initial lead was found to be important, and halogens (Cl, Br) in this position were found to improve affinity for the human receptor. The activity of a series of 2-halo-substituted benzylthioureas was then optimized by modification of the proline diphenylmethyl amide, guided by a simple conceptual model based on structural overlay between these early antagonists and NK1 selective peptides. In this way, aromatic amino acid amides were identified which had improved affinity with respect to the starting diphenylmethyl (DPM) amides. The first sub-nanomolar ligand for the human NK1 receptor which arose from this series, 4af, combined a 2-chlorobenzylthiourea unit with a 2-naphthylalanine amide. Contemporaneously it was discovered that the benzylthiourea unit could be simplified to a phenylthiourea providing that an appropriate 2-substituent was also incorporated. Combination of these two series gave 2-NO2 phenylthiourea analogues which led directly to the analogous urea, 5f(2-nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide, SDZ NKT 343), a highly potent ligand for the human NK1 receptor (K-i = 0.16 nM). In addition to its high in vitro potency, 5f proved to be a potent orally active analgesic in guinea pig models of chronic inflammatory and neuropathic pain. The nature of the 2-aryl substituent was found to be critical for oral activity in this series. Clinical evaluation of 5f as a novel analgesic agent is currently underway.

  DOI：

  10.1021/jm970499g

文献信息

• 2-Nitrophenylcarbamoyl-(<i>S</i>)-prolyl-(<i>S</i>)-3-(2-naphthyl)alanyl-<i>N</i>-benzyl-<i>N</i>- methylamide (SDZ NKT 343), a Potent Human NK₁ Tachykinin Receptor Antagonist with Good Oral Analgesic Activity in Chronic Pain Models
  作者：C. Walpole、S. Y. Ko、M. Brown、D. Beattie、E. Campbell、F. Dickenson、S. Ewan、G. A. Hughes、M. Lemaire、J. Lerpiniere、S. Patel、L. Urban

  DOI：10.1021/jm970499g

  日期：1998.8.1

  A lead compound which had sub-micromolar affinity for the rabbit NK1 receptor but negligible affinity for rat NK1 receptors, 3a, was discovered by directed screening. 2-Substitution in the ring of the benzylthiourea substituent in the initial lead was found to be important, and halogens (Cl, Br) in this position were found to improve affinity for the human receptor. The activity of a series of 2-halo-substituted benzylthioureas was then optimized by modification of the proline diphenylmethyl amide, guided by a simple conceptual model based on structural overlay between these early antagonists and NK1 selective peptides. In this way, aromatic amino acid amides were identified which had improved affinity with respect to the starting diphenylmethyl (DPM) amides. The first sub-nanomolar ligand for the human NK1 receptor which arose from this series, 4af, combined a 2-chlorobenzylthiourea unit with a 2-naphthylalanine amide. Contemporaneously it was discovered that the benzylthiourea unit could be simplified to a phenylthiourea providing that an appropriate 2-substituent was also incorporated. Combination of these two series gave 2-NO2 phenylthiourea analogues which led directly to the analogous urea, 5f(2-nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide, SDZ NKT 343), a highly potent ligand for the human NK1 receptor (K-i = 0.16 nM). In addition to its high in vitro potency, 5f proved to be a potent orally active analgesic in guinea pig models of chronic inflammatory and neuropathic pain. The nature of the 2-aryl substituent was found to be critical for oral activity in this series. Clinical evaluation of 5f as a novel analgesic agent is currently underway.