2-<<(2R,3S)-3-<(Boc-L-phenylalanyl-L-histidyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetic acid | 142843-23-0

• 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: 2-<<(2R,3S)-3-<(Boc-L-phenylalanyl-L-histidyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetic acid
• 英文别名: {3-[2-(2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-3-(1H-imidazol-4-yl)-propionylamino]-4-cyclohexyl-2-hydroxy-butylsulfanyl}-acetic acid; hydrate；2-[(2R,3S)-4-cyclohexyl-2-hydroxy-3-[[(2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoyl]amino]butyl]sulfanylacetic acid
• CAS: 142843-23-0
• 化学式: C₃₂H₄₇N₅O₇S
• 分子量: 645.82
• InChiKey: ZUFLKCVDEABOFS-FWEHEUNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  45
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  208
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-氨基奎宁 、 2-<<(2R,3S)-3-<(Boc-L-phenylalanyl-L-histidyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以32%的产率得到{(S)-1-[(S)-1-{(1S,2R)-3-[(1-Aza-bicyclo[2.2.2]oct-3-ylcarbamoyl)-methylsulfanyl]-1-cyclohexylmethyl-2-hydroxy-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：

  ethyl 2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetate 在 盐酸 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 2-<<(2R,3S)-3-<(Boc-L-phenylalanyl-L-histidyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetic acid
  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

文献信息

• US5114925A
  申请人：——

  公开号：US5114925A

  公开（公告）日：1992-05-19
• Inhibitors of human renin with C-termini derived from amides and esters of .alpha.-mercaptoalkanoic acids
  作者：Wallace T. Ashton、Christine L. Cantone、Richard L. Tolman、William J. Greenlee、Robert J. Lynch、Terry W. Schorn、John F. Strouse、Peter K. S. Siegl

  DOI：10.1021/jm00093a009

  日期：1992.7

  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.