[3-(2-tert-butoxy-2-oxoethyl)-2-oxoimidazolidin-1-yl]acetic acid | 291778-29-5

• 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: [3-(2-tert-butoxy-2-oxoethyl)-2-oxoimidazolidin-1-yl]acetic acid
• 英文别名: 2-[(3-tert-butoxycarbonylmethyl)-2-oxo-1-imidazolidinyl]acetic acid；2-(3-{[(tert-butyl)oxycarbonyl]methyl}-2-oxoimidazolidinyl)acetic acid；2-[3-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-2-oxoimidazolidin-1-yl]acetic acid
• CAS: 291778-29-5
• 化学式: C₁₁H₁₈N₂O₅
• 分子量: 258.274
• InChiKey: HUCDVVXSDARTFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [3-(2-tert-butoxy-2-oxoethyl)-2-oxoimidazolidin-1-yl]acetic acid 、 (1S)-L-valyl-N-<1-<(2-benzoxazolyl)hydroxymethyl>-2-methylpropyl>-L-prolinamide 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 tert-butyl 2-(3-(2-(((2S)-1-((2S)-2-(((2S)-1-(benzo[d]oxazol-2-yl)-1-hydroxy-3-methylbutan-2-yl)carbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)amino)-2-oxoethyl)-2-oxoimidazolidin-1-yl)acetate
  参考文献：
  名称：

  Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury

  摘要：

  A series of peptide-based transition-state human neutrophil elastase (HNE) inhibitors with N-terminal acidic moieties were synthesized and their inhibitory activity against HNE was evaluated both in vitro and in vivo. Our results show that compounds containing cyclic amide bridged acidic moieties at the N-terminal have not only improved water solubility but also high in vivo potency. Among these compounds, AE-3763 showed remarkable efficacy in hamster models of elastase-induced lung hemorrhage and lipopolysaccharide (LPS)-induced lung injury as well as in a mouse model of LPS/galactosamine-induced acute multiple organ dysfunctions. The water solubility of AE-3763 (>1000 mg/ml in H(2)O) was also far superior to that of any of the other compounds synthesized. Thus, it is believed that AE-3763 would be useful for treatment of HNE-associated respiratory disorders, such as acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and acute exacerbation of chronic obstructive pulmonary disease (COPD). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.020
• 作为产物：
  描述：

  di-tert-butyl 2,2'-(2-oxoimidazolidine-1,3-diyl)diacetate 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以32%的产率得到[3-(2-tert-butoxy-2-oxoethyl)-2-oxoimidazolidin-1-yl]acetic acid
  参考文献：
  名称：

  Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury

  摘要：

  A series of peptide-based transition-state human neutrophil elastase (HNE) inhibitors with N-terminal acidic moieties were synthesized and their inhibitory activity against HNE was evaluated both in vitro and in vivo. Our results show that compounds containing cyclic amide bridged acidic moieties at the N-terminal have not only improved water solubility but also high in vivo potency. Among these compounds, AE-3763 showed remarkable efficacy in hamster models of elastase-induced lung hemorrhage and lipopolysaccharide (LPS)-induced lung injury as well as in a mouse model of LPS/galactosamine-induced acute multiple organ dysfunctions. The water solubility of AE-3763 (>1000 mg/ml in H(2)O) was also far superior to that of any of the other compounds synthesized. Thus, it is believed that AE-3763 would be useful for treatment of HNE-associated respiratory disorders, such as acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and acute exacerbation of chronic obstructive pulmonary disease (COPD). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.020

文献信息

• Pyrrolidine derivatives and their use as chymase inhibitor
  申请人：——

  公开号：US20040102384A1

  公开（公告）日：2004-05-27

  Novel pyrrolidine derivatives, being useful as chymase inhibitor or intermediate for synthesis of the active compounds, which has the formula (I): wherein R 1 is cycloalkyl, substituted or unsubstituted phenyl or naphthyl, indanyl, thienyl, furyl, substituted or unsubstituted indolyl, benzofuryl, substituted or unsubstituted benzothienyl, etc.; R 2 is H, alkyl, phenyl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl; R 3 is (i) substituted or unsubstituted monocyclic heterocyclic group, (ii) substituted or unsubstituted, benzene- or pyridine-fused heterocyclic group, or (iii) a group (a): R 4 and R 5 are independently H or OH, but R 4 and R 5 are not simultaneously H, or both form oxo; n is 0, 1, 2 or 3; or a salt thereof. 1

  新型吡咯烷衍生物，可用作针对钳酶的抑制剂或合成活性化合物的中间体，其化学式为（I）：其中R1为环烷基，取代或未取代的苯基或萘基，吲哚基，噻吩基，呋喃基，取代或未取代的吲哚基，苯并呋喃基，取代或未取代的苯并噻吩基等；R2为H，烷基，苯基-低碳基，环烷基或环烷基-低碳基；R3为（i）取代或未取代的单环杂环基，（ii）取代或未取代的苯并或吡啶融合的杂环基，或（iii）一组（a）：R4和R5独立地为H或OH，但R4和R5不同时为H，或两者形成氧化物；n为0、1、2或3；或其盐。
• [EN] PYRROLIDINE DERIVATIVES AND THEIR USE AS CHYMASE INHIBITOR<br/>[FR] DERIVES DE LA PYRROLIDINE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA CHYMASE
  申请人：DAINIPPON PHARMACEUTICAL CO

  公开号：WO2002018378A1

  公开（公告）日：2002-03-07

  Novel pyrrolidine derivatives, being useful as chymase inhibitor or intermediate for synthesis of the active compounds, which has the formula (I): wherein R1 is cycloalkyl, substituted or unsubstituted phenyl or naphthyl, indanyl, thienyl, furyl, substituted or unsubstituted indolyl, benzofuryl, substituted or unsubstituted benzothienyl, etc.; R2 is H, alkyl, phenyl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl; R3 is (i) substituted or unsubstituted monocyclic heterocyclic group, (ii) substituted or unsubstituted, benzene- or pyridine-fused heterocyclic group, or (iii) a group (a): R?4 and R5¿ are independently H or OH, but R?4 and R5¿ are not simultaneously H, or both form oxo; n is 0, 1, 2 or 3; or a salt thereof.

  新型吡咯烷衍生物，可用作Chymase抑制剂或活性化合物的合成中间体，其化学式为（I）：其中，R1为环烷基，取代或未取代的苯基或萘基，茚基，噻吩基，呋喃基，取代或未取代的吲哚基，苯并呋喃基，取代或未取代的苯并噻吩基等；R2为H，烷基，苯基-低烷基，环烷基或环烷基-低烷基；R3为（i）取代或未取代的单环杂环基，（ii）取代或未取代的苯并或吡啶并杂环基，或（iii）一个基团（a）：R?4和R5¿独立地为H或OH，但R?4和R5¿不同时为H，或同时形成氧化物；n为0、1、2或3；或其盐。
• HETEROCYCLIC COMPOUNDS, INTERMEDIATES THEREOF AND ELASTASE INHIBITORS
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP1157998B1

  公开（公告）日：2004-02-11
• PYRROLIDINE DERIVATIVES AND THEIR USE AS CHYMASE INHIBITOR
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP1313730A1

  公开（公告）日：2003-05-28
• US6835714B1
  申请人：——

  公开号：US6835714B1

  公开（公告）日：2004-12-28