[(S)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-but-3-enyl]-carbamic acid tert-butyl ester | 145705-51-7

• 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)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-but-3-enyl]-carbamic acid tert-butyl ester
• CAS: 145705-51-7
• 化学式: C₂₄H₄₄N₂O₅
• 分子量: 440.624
• InChiKey: AVVORUIYLZGZOF-XSDIEEQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.68
• 重原子数：
  31.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  107.89
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [(S)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-but-3-enyl]-carbamic acid tert-butyl ester 在 盐酸 、 碳酸氢钠 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-[(S)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-but-3-enylcarbamoyl]-cyclopropanecarboxylic acid ethyl ester
  参考文献：
  名称：

  Design and Synthesis of Renin Inhibitors: Incorporation of Transition-State Isostere Side Chains That Span from the S1 to the S3 Binding Pockets and Examination of P3-Modified Renin Inhibitors

  摘要：

  A series of renin inhibitors were designed to examine the topography of the contiguous binding pocket of renin that is normally occupied by the P1 and P3 side chains. Molecular modeling suggested that extending the P1 hydrophobic side chain into the adjacent hydrophobic S3 enzyme pocket was feasible. Novel transition state isosteres with modified P1-->P3 side chains were synthesized and provided enhanced binding affinity when incorporated into renin inhibitors in which the P3 Phe was substituted by Gly. In a complementary approach, the binding affinities of a variety of P3-P4-modified peptidomimetic renin inhibitors that lacked substantial hydrophobic side chains at these sites were measured.

  DOI：

  10.1021/jm00015a012
• 作为产物：
  描述：

  (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane 、 Boc-L-烯丙基甘氨酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 [(S)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-but-3-enyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Design and Synthesis of Renin Inhibitors: Incorporation of Transition-State Isostere Side Chains That Span from the S1 to the S3 Binding Pockets and Examination of P3-Modified Renin Inhibitors

  摘要：

  A series of renin inhibitors were designed to examine the topography of the contiguous binding pocket of renin that is normally occupied by the P1 and P3 side chains. Molecular modeling suggested that extending the P1 hydrophobic side chain into the adjacent hydrophobic S3 enzyme pocket was feasible. Novel transition state isosteres with modified P1-->P3 side chains were synthesized and provided enhanced binding affinity when incorporated into renin inhibitors in which the P3 Phe was substituted by Gly. In a complementary approach, the binding affinities of a variety of P3-P4-modified peptidomimetic renin inhibitors that lacked substantial hydrophobic side chains at these sites were measured.

  DOI：

  10.1021/jm00015a012