(1S,2S)-N-<1-(cyclohexylmethyl)-2-(dimethoxyphosphinyl)-2-hydroxyethyl>-N²--L-phenylalanyl>-L-leucinamide | 131434-98-5

• 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: (1S,2S)-N-<1-(cyclohexylmethyl)-2-(dimethoxyphosphinyl)-2-hydroxyethyl>-N²--L-phenylalanyl>-L-leucinamide
• 英文别名: tert-butyl N-[(2S)-1-[[(2S)-1-[[(1S,2S)-3-cyclohexyl-1-dimethoxyphosphoryl-1-hydroxypropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 131434-98-5
• 化学式: C₃₁H₅₂N₃O₈P
• 分子量: 625.743
• InChiKey: FSYRWSZRSUVZIQ-VZTVMPNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  43
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  -<1-(cyclohexylmethyl)-2-(dimethoxyphosphinyl)-2-hydroxyethyl>carbamic acid, 1,1-dimethylethyl ester 在 盐酸 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 (1S,2S)-N-<1-(cyclohexylmethyl)-2-(dimethoxyphosphinyl)-2-hydroxyethyl>-N²--L-phenylalanyl>-L-leucinamide
  参考文献：
  名称：

  肽类α-羟基膦酸酯的制备-一种新型的过渡态类似物肾素抑制剂

  摘要：

  描述了α-羟基膦酸酯的立体选择性合成，这是一类新型的过渡态类似物抑制剂。讨论了在α-羟基-β-氨基二甲基膦酸酯8的N端掺入中性和碱性氨基酸残基的方法。在适用于天冬氨酰蛋白酶肾素的三肽构架中结合这种新颖的功能性导致了该酶的有效抑制剂的发展。

  DOI：

  10.1016/s0040-4039(00)97903-6

文献信息

• .alpha.-Hydroxy Phosphinyl-Based Inhibitors of Human Renin
  作者：Dinesh V. Patel、Katherine Rielly-Gauvin、Denis E. Ryono、Charles A. Free、W. Lynn Rogers、Sandra A. Smith、Jack M. DeForrest、Robert S. Oehl、Edward W. Petrillo

  DOI：10.1021/jm00022a022

  日期：1995.10

  The design and application of alpha-hydroxy phosphonates, a new class of transition state analogs, toward the discovery of novel and potent inhibitors of the aspartyl protease renin is described. Tripeptidic alpha-hydroxy diethyl phosphonate 3, the first example in this series, was found to be a good inhibitor of human renin (IC50 = 29 nM), and preliminary studies led to the choice of alpha-hydroxy dimethyl phosphonate 15 (IC50 = 16 nM) as a base-line compound for further structure-activity relationship study. Corresponding phosphinate (28-30) and phosphine oxide (23 and 24) analogs of 15 were prepared to assess the steric and electronic requirements around the phosphorus center. Evaluation of these analogs suggested that the presence of at least one alkoxy group on phosphorus was a critical requirement for good activity. Inhibitors with leucine at P-2 possessed better in vitro activity than the corresponding P-2 histidine analogs (15, IC50 = 16 nM vs 37, IC50 = 220 nM; 33, IC50 = 8.5 nM vs 40, IC50 = 41 nM). Compound 34 (IC50 = 31 nM), the P-3 aminocaproic analog of 15, showed complete and long-lasting inhibition of plasma renin activity while eliciting a 10-15 mmHg drop in mean arterial pressure when administered intravenously at 1 mu mol/kg in conscious, sodium-depleted, cynomolgus monkeys. In summary, the alpha-hydroxy phosphonates represent a promising and structurally novel class of transition state analog inhibitors of human renin.
• Preparation of peptidic α-hydroxy phosphonates a new class of transition state analog renin inhibitors
  作者：Dinesh V. Patel、Katherine Rielly-Gauvin、Denis E. Ryono

  DOI：10.1016/s0040-4039(00)97903-6

  日期：——

  A stereoselective synthesis of α-hydroxy phosphonates, a new class of transition state analog inhibitors is described. Methods of incorporating neutral and basic amino acid residues at the N-terminus of α-hydroxy-β-amino dimethyl phosphonate 8 are discussed. Incorporation of this novel functionality in a tripeptidic framework suitable for the aspartyl protease renin has led to the development of potent

  描述了α-羟基膦酸酯的立体选择性合成，这是一类新型的过渡态类似物抑制剂。讨论了在α-羟基-β-氨基二甲基膦酸酯8的N端掺入中性和碱性氨基酸残基的方法。在适用于天冬氨酰蛋白酶肾素的三肽构架中结合这种新颖的功能性导致了该酶的有效抑制剂的发展。