4-<2-<2-<<(2R,3S)-3-<α,N^im-bis(tert-butoxycarbonyl)-L-histidyl>amino>-4-cyclohexyl-2-hydroxy-1-butyl>sulfonyl>acetamido>ethyl>morpholine | 142843-13-8

• 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-<2-<2-<<(2R,3S)-3-<α,N^im-bis(tert-butoxycarbonyl)-L-histidyl>amino>-4-cyclohexyl-2-hydroxy-1-butyl>sulfonyl>acetamido>ethyl>morpholine
• 英文别名: 4-{2-[2-({(2R,3S)-3-[(N^α,N^im-bis(tert-butoxycarbonyl)-L-histidyl)amino]-4-cyclohexyl-2-hydroxy-1-butyl}sulfonyl)acetamido]ethyl}morpholine；tert-butyl 4-[(2S)-3-[[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[2-(2-morpholin-4-ylethylamino)-2-oxoethyl]sulfonylbutan-2-yl]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]imidazole-1-carboxylate
• CAS: 142843-13-8
• 化学式: C₃₄H₅₈N₆O₁₀S
• 分子量: 742.935
• InChiKey: ISARFXBBLLAVGB-KCHLEUMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.78
• 重原子数：
  51.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  207.49
• 氢给体数：
  4.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  4-<2-<2-<<(2R,3S)-3-<α,N^im-bis(tert-butoxycarbonyl)-L-histidyl>amino>-4-cyclohexyl-2-hydroxy-1-butyl>sulfonyl>acetamido>ethyl>morpholine 在 三氟乙酸 作用下， 反应 4.0h， 生成 (2S)-2-amino-N-[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[2-(2-morpholin-4-ylethylamino)-2-oxoethyl]sulfonylbutan-2-yl]-3-(1H-imidazol-5-yl)propanamide
  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：

  4-<2-<2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetamido>ethyl>morpholine 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 73.5h， 生成 4-<2-<2-<<(2R,3S)-3-<α,N^im-bis(tert-butoxycarbonyl)-L-histidyl>amino>-4-cyclohexyl-2-hydroxy-1-butyl>sulfonyl>acetamido>ethyl>morpholine
  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