<(1-methyl-1H-indol-3-yl)carbonyl>-(2S,4R)Hyp-Trp(CHO)-NMeBzl | 158574-82-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: <(1-methyl-1H-indol-3-yl)carbonyl>-(2S,4R)Hyp-Trp(CHO)-NMeBzl
• 英文别名: (2S,4R)-N-[(2S)-1-[benzyl(methyl)amino]-3-(1-formylindol-3-yl)-1-oxopropan-2-yl]-4-hydroxy-1-(1-methylindole-3-carbonyl)pyrrolidine-2-carboxamide
• CAS: 158574-82-4
• 化学式: C₃₅H₃₅N₅O₅
• 分子量: 605.693
• InChiKey: IXSRTEYBDXVZPF-ISXOHIFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  <(1-methyl-1H-indol-3-yl)carbonyl>-(2S,4R)Hyp-Trp(CHO)-NMeBzl 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 0.33h， 以89.4%的产率得到<(1-methyl-1H-indol-3-yl)carbonyl>-(2S,4R)Hyp-Trp-NMeBzl
  参考文献：
  名称：

  Studies on Neurokinin Antagonists. 4. Synthesis and Structure-Activity Relationships of Novel Dipeptide Substance P Antagonists: N2-[(4R)-4-Hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N-methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and Its Related Compounds

  摘要：

  As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N-2-[N-2-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenylmethyl)-L-phenylalaninamide (2b). The lysine part in 2b was first optimized to a (2S,4R)hydroxyproline derivative (3h),which is 2-fold more potent than 2b in [H-3]SP binding assay using guinea pig lung membranes. Next we modified the 1H-indol-3-ylcarbonyl part in 3h. Introduction; of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity. Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.

  DOI：

  10.1021/jm00039a022
• 作为产物：
  描述：

  Boc-L-羟脯氨酸 在 盐酸 、 1-羟基苯并三唑 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 <(1-methyl-1H-indol-3-yl)carbonyl>-(2S,4R)Hyp-Trp(CHO)-NMeBzl
  参考文献：
  名称：

  Studies on Neurokinin Antagonists. 4. Synthesis and Structure-Activity Relationships of Novel Dipeptide Substance P Antagonists: N2-[(4R)-4-Hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N-methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and Its Related Compounds

  摘要：

  As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N-2-[N-2-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenylmethyl)-L-phenylalaninamide (2b). The lysine part in 2b was first optimized to a (2S,4R)hydroxyproline derivative (3h),which is 2-fold more potent than 2b in [H-3]SP binding assay using guinea pig lung membranes. Next we modified the 1H-indol-3-ylcarbonyl part in 3h. Introduction; of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity. Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.

  DOI：

  10.1021/jm00039a022