4-<2-<2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetamido>ethyl>morpholine | 142843-12-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-<2-<2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetamido>ethyl>morpholine
• 英文别名: 4-[2-[2-[[(2R,3S)-3-[t-Butoxycarbonylamino)-4-cyclohexyl-2-hydroxy-1-butyl]sulfonyl]acetamido]ethyl]-morpholine；4-{2-[2-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-4-cyclohexyl-2-hydroxy-1-butyl}thio)acetamido]ethyl}morpholine；tert-butyl N-[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[2-(2-morpholin-4-ylethylamino)-2-oxoethyl]sulfonylbutan-2-yl]carbamate
• CAS: 142843-12-7
• 化学式: C₂₃H₄₃N₃O₇S
• 分子量: 505.676
• InChiKey: KORNQGZSKRCEND-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-<2-<2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>acetamido>ethyl>morpholine 在 三氟乙酸 作用下， 反应 1.5h， 生成 2-[(2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyl]sulfonyl-N-(2-morpholin-4-ylethyl)acetamide
  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 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 49.5h， 生成 4-<2-<2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>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

文献信息

• Renin inhibitors containing the
  申请人：Merck & Co., Inc.

  公开号：US05114925A1

  公开（公告）日：1992-05-19

  Compounds of the formula: ##STR1## which are potent inhibitors of human renin and are useful for treating various forms of renin-associated hypertension, hyperaldosteronism and congestive heart failure; compositions containing these renin-inhibitory compounds, optionally with other antihypertensive agents; and methods of treating hypertension, hyperaldosteronism or congestive heart failure or of establishing renin as a causative factor in these conditions which employ these novel compounds.

  这是一段关于化合物的公式的描述：##STR1## 这些化合物是有效的人类肾素抑制剂，可用于治疗各种与肾素相关的高血压、高醛固酮症和充血性心力衰竭；包含这些肾素抑制剂化合物的组合物，可选地与其他降压药物一起使用；以及使用这些新型化合物治疗高血压、高醛固酮症或充血性心力衰竭或确定肾素是这些疾病的原因的方法。
• US5114925A
  申请人：——

  公开号：US5114925A

  公开（公告）日：1992-05-19