4-((S)-2-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-2-{(1S,2R)-1-cyclohexylmethyl-2-hydroxy-3-[(1-oxy-1-aza-bicyclo[2.2.2]oct-3-ylcarbamoyl)-methanesulfonyl]-propylcarbamoyl}-ethyl)-imidazole-1-carboxylic acid tert-butyl ester | 142843-22-9

• 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: 4-((S)-2-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-2-{(1S,2R)-1-cyclohexylmethyl-2-hydroxy-3-[(1-oxy-1-aza-bicyclo[2.2.2]oct-3-ylcarbamoyl)-methanesulfonyl]-propylcarbamoyl}-ethyl)-imidazole-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-[(2S)-3-[[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[2-[(1-oxido-1-azoniabicyclo[2.2.2]octan-3-yl)amino]-2-oxoethyl]sulfonylbutan-2-yl]amino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-oxopropyl]imidazole-1-carboxylate
• CAS: 142843-22-9
• 化学式: C₄₄H₆₇N₇O₁₁S
• 分子量: 902.122
• InChiKey: ZIBKBIVAFLIECW-FAMNIRKMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  63.0
• 可旋转键数：
  17.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  247.18
• 氢给体数：
  5.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  4-((S)-2-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-2-{(1S,2R)-1-cyclohexylmethyl-2-hydroxy-3-[(1-oxy-1-aza-bicyclo[2.2.2]oct-3-ylcarbamoyl)-methanesulfonyl]-propylcarbamoyl}-ethyl)-imidazole-1-carboxylic acid tert-butyl ester 在 氨 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以24%的产率得到{(S)-1-[(S)-1-{(1S,2R)-1-Cyclohexylmethyl-2-hydroxy-3-[(1-oxy-1-aza-bicyclo[2.2.2]oct-3-ylcarbamoyl)-methanesulfonyl]-propylcarbamoyl}-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Inhibitors of human renin with C-termini derived from amides and esters of .alpha.-mercaptoalkanoic acids

  摘要：

  New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. The corresponding sulfoxide and sulfone analogues were also investigated. Some of these derivatives, including one with a stable BocPhe replacement, were relatively potent inhibitors of human plasma renin, having IC50 values below 10 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys (Macaca mulatta) at 0.06-1 mg/kg, they reduced plasma renin activity by 87-94%. However, the accompanying drop in blood pressure was of short duration.

  DOI：

  10.1021/jm00093a009
• 作为产物：
  描述：

  3-氨基奎宁 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 22.5h， 生成 4-((S)-2-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-2-{(1S,2R)-1-cyclohexylmethyl-2-hydroxy-3-[(1-oxy-1-aza-bicyclo[2.2.2]oct-3-ylcarbamoyl)-methanesulfonyl]-propylcarbamoyl}-ethyl)-imidazole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Inhibitors of human renin with C-termini derived from amides and esters of .alpha.-mercaptoalkanoic acids

  摘要：

  New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. The corresponding sulfoxide and sulfone analogues were also investigated. Some of these derivatives, including one with a stable BocPhe replacement, were relatively potent inhibitors of human plasma renin, having IC50 values below 10 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys (Macaca mulatta) at 0.06-1 mg/kg, they reduced plasma renin activity by 87-94%. However, the accompanying drop in blood pressure was of short duration.

  DOI：

  10.1021/jm00093a009