tert-butyl N-[cyclohexylmethyl-[(2S,3S)-3-[[(2S)-2-(ethoxycarbonylamino)-3-methylbutanoyl]amino]-2-hydroxy-4-phenylbutyl]amino]carbamate | 180462-97-9

• 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-[cyclohexylmethyl-[(2S,3S)-3-[[(2S)-2-(ethoxycarbonylamino)-3-methylbutanoyl]amino]-2-hydroxy-4-phenylbutyl]amino]carbamate
• CAS: 180462-97-9
• 化学式: C₃₀H₅₀N₄O₆
• 分子量: 562.75
• InChiKey: KHTNFBBRXYXKSW-GSDHBNRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  40
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 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-[cyclohexylmethyl-[(2S,3S)-3-[[(2S)-2-(ethoxycarbonylamino)-3-methylbutanoyl]amino]-2-hydroxy-4-phenylbutyl]amino]carbamate 在 1,4-二氧六环 、 盐酸 作用下， 反应 2.0h， 以98%的产率得到
  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：

  1-[2(S)-hydroxy-3(S)-(trifluoroacetylamino)-4-phenyl-butyl]-1-[cyclohexylmethyl]-2-[tert-butoxycarbonyl]-hydrazine 在 1-ethyl-3-(3-diaminopropyl)carbodiimide hydrochloride 、 potassium carbonate 、 1-羟基苯并三唑一水物 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 32.5h， 生成 tert-butyl N-[cyclohexylmethyl-[(2S,3S)-3-[[(2S)-2-(ethoxycarbonylamino)-3-methylbutanoyl]amino]-2-hydroxy-4-phenylbutyl]amino]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