ethyl 2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>sulfonyl>acetate | 142843-09-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 磺酰类
• 英文名称: ethyl 2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>sulfonyl>acetate
• 英文别名: Ethyl 2-[[(2R,3S)-3-(t Butoxycarbonylamino)-4-cyclohexyl-2-hydroxy-1-butyl]sulfonyl]acetate；ethyl 2-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-4-cyclohexyl-2-hydroxy-1-butyl}sulfonyl)acetate；ethyl 2-[[(2R,3S) 3-(t butoxycarbonylamino)-4-cyclohexyl-2-hydroxy-1-butyl]sulfonyl]acetate；ethyl 2-[(2R,3S)-4-cyclohexyl-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]sulfonylacetate
• CAS: 142843-09-2
• 化学式: C₁₉H₃₅NO₇S
• 分子量: 421.555
• InChiKey: BIEUXOWKLVQRSL-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>sulfonyl>acetate 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 {1-[1-{1-Cyclohexylmethyl-2-hydroxy-3-[(2-morpholin-4-yl-ethylcarbamoyl)-methanesulfonyl]-propylcarbamoyl}-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester; hydrate
  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 1.5h， 以89%的产率得到ethyl 2-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>sulfonyl>acetate
  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
• 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.