(S)-N¹-{(1S,2S)-1-Benzyl-2-hydroxy-3-[N-(4-methoxy-benzyl)-hydrazino]-propyl}-2-[(quinoline-2-carbonyl)-amino]-succinamide | 161852-71-7

• 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: (S)-N¹-{(1S,2S)-1-Benzyl-2-hydroxy-3-[N-(4-methoxy-benzyl)-hydrazino]-propyl}-2-[(quinoline-2-carbonyl)-amino]-succinamide
• 英文别名: (2S)-N-[(2S,3S)-4-[amino-[(4-methoxyphenyl)methyl]amino]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide
• CAS: 161852-71-7
• 化学式: C₃₂H₃₆N₆O₅
• 分子量: 584.675
• InChiKey: NGACGQYHADHRMF-AWCRTANDSA-N

物化性质

• 沸点：
  986.1±65.0 °C(predicted)
• 密度：
  1.296±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  173
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  CBZ-L-缬氨酸 、 (S)-N¹-{(1S,2S)-1-Benzyl-2-hydroxy-3-[N-(4-methoxy-benzyl)-hydrazino]-propyl}-2-[(quinoline-2-carbonyl)-amino]-succinamide 在 N-甲基吗啉 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 以77%的产率得到{(S)-1-[N'-((2S,3S)-3-{(S)-3-Carbamoyl-2-[(quinoline-2-carbonyl)-amino]-propionylamino}-2-hydroxy-4-phenyl-butyl)-N'-(4-methoxy-benzyl)-hydrazinocarbonyl]-2-methyl-propyl}-carbamic acid benzyl ester
  参考文献：
  名称：

  Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability

  摘要：

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.

  DOI：

  10.1021/jm960022p
• 作为产物：
  描述：

  N-[(4-甲氧基苯基)甲基氨基]氨基甲酸叔丁酯 在 N-甲基吗啉 、 甲酸 、 potassium carbonate 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 73.0h， 生成 (S)-N¹-{(1S,2S)-1-Benzyl-2-hydroxy-3-[N-(4-methoxy-benzyl)-hydrazino]-propyl}-2-[(quinoline-2-carbonyl)-amino]-succinamide
  参考文献：
  名称：

  Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability

  摘要：

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.

  DOI：

  10.1021/jm960022p

文献信息

• Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability
  作者：Alexander Fässler、Guido Bold、Hans-Georg Capraro、Robert Cozens、Jürgen Mestan、Bernard Poncioni、Johannes Rösel、Marina Tintelnot-Blomley、Marc Lang

  DOI：10.1021/jm960022p

  日期：1996.1.1

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.