BOC-N-(1-piperazinylsulfonyl)-L-phenylalanine | 131099-50-8

• 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: BOC-N-(1-piperazinylsulfonyl)-L-phenylalanine
• 英文别名: (2S)-2-[[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]sulfonylamino]-3-phenylpropanoic acid
• CAS: 131099-50-8
• 化学式: C₁₈H₂₇N₃O₆S
• 分子量: 413.495
• InChiKey: WWQXQOIBGDQLBS-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  BOC-N-(1-piperazinylsulfonyl)-L-phenylalanine 、 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-<<4-<(1,1-dimethylethoxy)carbonyl>-1-piperazinyl>sulfonyl>-L-phenylalanyl-N-<1-(cyclohexylmethyl)-3,3-difluoro-2(R)-hydroxy-4-<(2-methylbutyl)amino>-4-oxobutyl>-4,5-didehydro-L-norvalinamide
  参考文献：
  名称：

  Design and synthesis of potent, selective, and orally active fluorine-containing renin inhibitors

  摘要：

  A series of primate renin inhibitors containing difluorocarbinol and difluoroketone groups at the P1-P1' position have been synthesized and studied both in vitro and in vivo. In vitro, the compounds were evaluated as inhibitors of monkey renin and the closely related aspartic proteinase, cathepsin D (bovine), as a measure of enzyme selectivity. Interestingly, the difluoroketone derivatives showed greatly reduced selectivity compared with the corresponding alcohols. However, selectivity could be enhanced by judicious choice of other substituents. Sites influencing selectivity, included not only P2, Which is well-known to strongly affect selectivity, but also the P4, P1-P1', and P2' sites. These results make possible the design of inhibitors with a greater selectivity for either renin versus cathepsin D. In vivo several of the compounds in the difluoroketone series have shown good oral activity in the salt depleted normotensive cynomolgus monkey model.

  DOI：

  10.1021/jm00079a001

文献信息

• Renin inhibitors containing C-terminal dihydroxy amides
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0380805A1

  公开（公告）日：1990-08-08

  The invention concerns novel renin-inhibitory peptides which are useful for treating renin-associated hypertension, congestive heart failure, hyperaldosteronism, glaucoma and diseases caused by retroviruses. Processes for preparing the peptides novel intermediates in the processes, compositions containing them, and methods of using them are included. Also included is a diagnostic method which uses the compounds to determine the presence of renin-associated hypertension, or hyperaldosteronism.

  本发明涉及新型肾素抑制肽，可用于治疗肾素相关性高血压、充血性心力衰竭、高醛固酮症、青光眼和逆转录病毒引起的疾病。包括制备肽的工艺、工艺中的新型中间体、含有肽的组合物和使用方法。此外，还包括一种诊断方法，利用这些化合物来确定是否存在肾素相关性高血压或高醛固酮症。
• US5198426A
  申请人：——

  公开号：US5198426A

  公开（公告）日：1993-03-30
• [EN] RENIN INHIBITORS CONTAINING C-TERMINAL DIHYDROXY AMIDES
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1990007521A1

  公开（公告）日：1990-07-12

  (EN) The invention concerns novel renin-inhibitory peptides which are useful for treating renin-associated hypertension, congestive heart failure, hyperaldosteronism, glaucoma and diseases caused by retroviruses. Processes for preparing the peptides novel intermediates in the processes, compositions containing them, and methods of using them are included. Also included is a diagnostic method which uses the compounds to determine the presence of renin-associated hypertension, or hyperaldosteronism.(FR) L'invention concerne de nouveaux peptides inhibiteurs de rénine utiles pour traiter l'hypertension associée à la rénine, l'insuffisance cardiaque, l'hyperaldostéronisme, le glaucome et des maladies provoquées par des rétrovirus. Elle concerne également des procédés de préparation des nouveaux intermédiaires des peptides dans les procédés, des compositions les contenant, ainsi que leurs modes d'utilisation. L'invention concerne en outre un procédé de diagnostic utilisant les composés pour déterminer la présence d'hypertension associée à la rénine, ou d'hyperaldostéronisme.
• Design and synthesis of potent, selective, and orally active fluorine-containing renin inhibitors
  作者：Annette M. Doherty、Ila Sircar、Brian E. Kornberg、John Quin、R. Thomas Winters、James S. Kaltenbronn、Michael D. Taylor、Brian L. Batley、Stephen R. Rapundalo

  DOI：10.1021/jm00079a001

  日期：1992.1

  A series of primate renin inhibitors containing difluorocarbinol and difluoroketone groups at the P1-P1' position have been synthesized and studied both in vitro and in vivo. In vitro, the compounds were evaluated as inhibitors of monkey renin and the closely related aspartic proteinase, cathepsin D (bovine), as a measure of enzyme selectivity. Interestingly, the difluoroketone derivatives showed greatly reduced selectivity compared with the corresponding alcohols. However, selectivity could be enhanced by judicious choice of other substituents. Sites influencing selectivity, included not only P2, Which is well-known to strongly affect selectivity, but also the P4, P1-P1', and P2' sites. These results make possible the design of inhibitors with a greater selectivity for either renin versus cathepsin D. In vivo several of the compounds in the difluoroketone series have shown good oral activity in the salt depleted normotensive cynomolgus monkey model.