tert-butyl N-[(2S,3S)-3-hydroxy-4-[[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-(2-methylpropyl)amino]-1-phenylbutan-2-yl]carbamate | 180463-07-4

• 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: tert-butyl N-[(2S,3S)-3-hydroxy-4-[[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-(2-methylpropyl)amino]-1-phenylbutan-2-yl]carbamate
• CAS: 180463-07-4
• 化学式: C₃₂H₄₈N₄O₆
• 分子量: 584.756
• InChiKey: FEMYAWIHYIRNRS-KCHLEUMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  42
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S,3S)-3-hydroxy-4-[[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-(2-methylpropyl)amino]-1-phenylbutan-2-yl]carbamate 在 palladium on activated charcoal N-甲基吗啉 、 甲酸 、 1-ethyl-3-(3-diaminopropyl)carbodiimide hydrochloride 、 氢气 、 1-羟基苯并三唑一水物 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 5.0~25.0 ℃ 、101.33 kPa 条件下， 反应 41.0h， 生成 (2S)-N-[(2S,3S)-4-[[[(2S)-2-amino-3-methylbutanoyl]amino]-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide
  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：

  <(benzyloxycarbonyl)-L-valinyl>hydrazinecarboxylic acid tert-butyl ester 在 盐酸 、 sodium cyanoborohydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 49.0h， 生成 tert-butyl N-[(2S,3S)-3-hydroxy-4-[[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-(2-methylpropyl)amino]-1-phenylbutan-2-yl]carbamate
  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