{(S)-1-[(S)-1-((1S,2S)-1-Cyclohexylmethyl-2-hydroxy-3-phenylcarbamoyl-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester | 143122-37-6

• 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-[(S)-1-((1S,2S)-1-Cyclohexylmethyl-2-hydroxy-3-phenylcarbamoyl-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S,3S)-5-anilino-1-cyclohexyl-3-hydroxy-5-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 143122-37-6
• 化学式: C₃₇H₅₀N₆O₆
• 分子量: 674.841
• InChiKey: CGBAPJGYOGMQRS-YDPTYEFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  49
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  175
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ((S)-1-{(S)-1-((1S,2S)-1-Cyclohexylmethyl-2-hydroxy-3-phenylcarbamoyl-propylcarbamoyl)-2-[1-(2,4-dinitro-phenyl)-1H-imidazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethyl)-carbamic acid tert-butyl ester 在 苯硫酚 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 {(S)-1-[(S)-1-((1S,2S)-1-Cyclohexylmethyl-2-hydroxy-3-phenylcarbamoyl-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'

  摘要：

  A series of renin inhibitors containing new P1-P1' dipeptide mimetics are presented The P1-P1' mimetics were obtained from (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-[(omega-mesyloxy)alkyl]-2,2-dimethyloxazolidines 5b, 9, and 11b by nucleophilic substitution of the mesylate groups with the sodium salts of mercapto- and hydroxyheterocycles. Removal of the protecting groups and stepwise acylations with amino acid derivatives provided renin inhibitors with a length of a tripeptide. Replacement of P2 histidine by other amino acids maintained or enhanced renin inhibitory potency. By alteration of P3 phenylalanine, compounds with IC50 values in the nanomolar range and stability against chymotrypsin were obtained. Finally, the effect of the C-terminal heterocycle on the renin inhibition was studied. Compound XVII was examined in vivo for its hypotensive effects. In salt-depleted cynomolgus monkeys, XVII inhibited plasma renin activity and lowered blood pressure after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00097a010