2S-(1-Pyrrolidin-2,5-dionyl)-3-methyl-butanoic acid benzyl ester | 192725-70-5

• 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: 2S-(1-Pyrrolidin-2,5-dionyl)-3-methyl-butanoic acid benzyl ester
• 英文别名: 2S-(1-pyrrolidin-2,5-dionyl)-3-methylbutanoic acid benzyl ester；benzyl (2S)-2-(2,5-dioxopyrrolidin-1-yl)-3-methylbutanoate
• CAS: 192725-70-5
• 化学式: C₁₆H₁₉NO₄
• 分子量: 289.331
• InChiKey: HDXUOZYPJNCZII-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  63.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2S-(1-Pyrrolidin-2,5-dionyl)-3-methyl-butanoic acid benzyl ester 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-pyrrolidin-2,5-dionyl)-3-methyl-butanoyl)amino-1,6-diphenylhexane
  参考文献：
  名称：

  Novel lopinavir analogues incorporating heterocyclic replacements of six-member cyclic urea––synthesis and structure–activity relationships

  摘要：

  The HIV protease inhibitor ABT-378 (lopinavir) has a six-member cyclic urea in the P-2 position. A series of analogues in which the six-member cyclic urea is replaced by various heterocycles was synthesized and the structure-activity relationships explored. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.089
• 作为产物：
  描述：

  L-缬氨酸苄酯 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 生成 2S-(1-Pyrrolidin-2,5-dionyl)-3-methyl-butanoic acid benzyl ester
  参考文献：
  名称：

  Novel lopinavir analogues incorporating heterocyclic replacements of six-member cyclic urea––synthesis and structure–activity relationships

  摘要：

  The HIV protease inhibitor ABT-378 (lopinavir) has a six-member cyclic urea in the P-2 position. A series of analogues in which the six-member cyclic urea is replaced by various heterocycles was synthesized and the structure-activity relationships explored. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.089

文献信息

• Retroviral protease inhibiting compounds
  申请人：Abbott Laboratories

  公开号：EP1170289A2

  公开（公告）日：2002-01-09

  A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.

  披露了一种包含公式（II）取代基的化合物，作为一种HIV蛋白酶抑制剂。还披露了用于制造此类化合物的中间体以及制造此类中间体的过程。
• USE OF PRODRUGS TO AVOID GI MEDIATED ADVERSE EVENTS
  申请人：Franklin Richard

  公开号：US20120202756A1

  公开（公告）日：2012-08-09

  The present invention relates to prodrugs of a wide variety of drugs and pharmaceutical compositions containing such prodrugs. Methods for minimizing locally mediated (from within the gut lumen) adverse gastrointestinal events associated with the underivatised drug and increasing the sustainment of plasma drug levels with the aforementioned prodrugs are also provided. Thus, the present invention relates to the use of prodrugs of a wide diversity of drugs (other than opioids) to transiently inactivate them and so reduce directly, locally mediated adverse gastrointestinal (GI) side-effects normally evident after administration of the parent compound. Additionally, such prodrugs may confer improved pharmacokinetics.

  本发明涉及各种药物的前药和含有这些前药的制药组合物。还提供了一种方法，用于最小化与未衍生药物相关的局部介导（来自肠腔内）不良胃肠事件，并使用上述前药增加血浆药物水平的持续性。因此，本发明涉及使用各种药物（除阿片类药物外）的前药，以短暂地使它们失活，从而减少通常在给予原始化合物后出现的直接、局部介导的不良胃肠（GI）副作用。此外，这些前药可能提供改善的药代动力学。
• RETROVIRAL PROTEASE INHIBITING COMPOUNDS
  申请人：Abbott Laboratories

  公开号：EP0882024B1

  公开（公告）日：2002-02-06
• NOVEL DICARBOXYLIC ACID LINKED AMINO ACID AND PEPTIDE PRODRUGS OF OPIOIDS AND USES THEREOF
  申请人：Franklin Richard

  公开号：US20100286186A1

  公开（公告）日：2010-11-11

  The present invention concerns dicarboxylic acid linked amino acid and peptide prodrugs of opioid analgesics and pharmaceutical compositions containing such prodrugs. Methods for providing pain relief, decreasing the adverse GI side effects of the opioid analgesic and increasing the bioavailability of the opioid analgesic with the aforementioned prodrugs are also provided. In one embodiment, prodrugs having the amino acid side chains of valine, leucine, isoleucine and glycine; and mono-, di- and tripeptides thereof are provided.
• US5914332A
  申请人：——

  公开号：US5914332A

  公开（公告）日：1999-06-22