(2,4,5-trioxo-3-phenethyl-imidazolidin-1-yl)ethanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (2,4,5-trioxo-3-phenethyl-imidazolidin-1-yl)ethanoic acid
• 英文别名: 3-Carboxymethyl-1-(2-phenylethyl)parabanic acid；2-[2,4,5-Trioxo-3-(2-phenylethyl)imidazolidin-1-yl]acetic acid
• 化学式: C₁₃H₁₂N₂O₅
• 分子量: 276.249
• InChiKey: KGNDNCQUKBGVSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  95
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-苯乙胺盐酸盐 在 盐酸 、 氢氧化钾 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 18.5h， 生成 (2,4,5-trioxo-3-phenethyl-imidazolidin-1-yl)ethanoic acid
  参考文献：
  名称：

  Highly Selective Aldose Reductase Inhibitors. 1. 3-(Arylalkyl)-2,4,5-trioxoimidazolidine-1-acetic Acids

  摘要：

  A series of 3-(arylalkyl)-2,4,5-trioxoimidazolidine-1-acids (1) was prepared and tested for aldose reductase (AR) and aldehyde reductase (ALR) inhibitory activities. These compounds showed strong inhibitory activity against AR without significant inhibitory activity for ALR. The ratio of IC50(ALR)/IC50(AR) was > 1000 in some compouds. On the basis of pharmacological tests such as the recovery of reduced motor nerve conduction velocity and toxicological profile, 3-(3-nitrobenzyl)-2,4,5-trioxoimidazolidine-1-acid (NZ-314) was selected as the candidate for clinical development.

  DOI：

  10.1021/jm9508393

文献信息

• Structure–activity relationship of 2,4,5-trioxoimidazolidines as inhibitors of thymidine phosphorylase
  作者：Mehdi Rajabi、David Mansell、Sally Freeman、Richard A. Bryce

  DOI：10.1016/j.ejmech.2011.01.035

  日期：2011.4

  thymidine phosphorylase, have been identified using molecular modelling, synthesis and biological evaluation. These inhibitors are 2,4,5-trioxoimidazolidines bearing N-(substituted)phenylalkyl groups, together with, in most cases, N′-(CH2)n-carboxylic acid, ester or amide side chains. The best compound from this series is 3-(2,4,5-trioxo-3-phenylethyl-imidazolodin-1-yl)propionamide, with an IC50 of

  使用分子建模，合成和生物学评估，已鉴定出血管生成酶的新型非核碱基衍生抑制剂胸苷磷酸化酶。这些抑制剂是带有N-（取代的）苯基烷基以及在大多数情况下N '-（CH 2）n-羧酸，酯或酰胺侧链的2,4,5-三氧代咪唑烷。该系列中最好的化合物是3-（2,4,5-三氧代-3-苯基乙基-咪唑啉-1-基）丙酰胺，对大肠杆菌的IC 50为40μMTP。分子建模表明，该配体与闭口的人类TP络合时，在活性位点区域的苯烷基通常被含胸腺嘧啶的结构占据。
• Parabanic acid derivatives and pharmaceutical compositions containing them
  申请人：NIPPON ZOKI PHARMACEUTICAL CO. LTD.

  公开号：EP0353198A1

  公开（公告）日：1990-01-31

  The present invention relates to parabanic acid derivatives and pharmaceutically acceptable salts and metal complexes thereof having aldose reductase inhibitory activity. The compounds have the formula The compounds are useful as drugs for the treatment or prevention of diabetic conditions.

  本发明涉及具有醛糖还原酶抑制活性的对位苯甲酸衍生物及其药学上可接受的盐和金属复合物。这些化合物的化学式为 这些化合物可用作治疗或预防糖尿病的药物。
• 3-Deoxyglucosone production inhibitor
  申请人：NIPPON ZOKI PHARMACEUTICAL CO., LTD.

  公开号：EP0855182A1

  公开（公告）日：1998-07-29

  The present invention relates to an inhibitor for the production of 3-deoxyglucosone (3-DG) which contains at least one of parabanic acid derivatives represented by the following formula (I) or pharmaceutically acceptable salts thereof as an effective ingredient    wherein R is hydrogen or lower alkyl; X is hydrogen, alkyl, cycloalkyl, lower alkylcycloalkyl, phenyl or phenylalkyl which is optionally substituted with lower alkyl, lower alkoxy, nitro and/or halogen; and n is an integer of from 1 to 4. The compound of the present invention has an action of inhibiting the production of 3-DG which is a highly active intermediate and participates in a protein crosslinked formation in Maillard reaction and, therefore, said compound is useful in the treatment and the prevention of various diseases induced by deposition into tissues or sclerosis or denaturation of crosslinked protein, similar diseases induced by aging and diabetic complications.

  本发明涉及一种生产 3-脱氧葡萄糖苷（3-DG）的抑制剂，它含有下式（I）所代表的至少一种对位苯甲酸衍生物或其药学上可接受的盐作为有效成分 其中 R 是氢或低级烷基；X 是氢、烷基、环烷基、低级烷基环烷基、苯基或苯基烷基，可任选被低级烷基、低级烷氧基、硝基和/或卤素取代；n 是 1 至 4 的整数。 本发明的化合物具有抑制 3-DG 生成的作用，3-DG 是一种高活性的中间体，参与 Maillard 反应中蛋白质交联的形成，因此，本发明的化合物可用于治疗和预防由组织沉积或硬化或交联蛋白质变性引起的各种疾病、由衰老和糖尿病并发症引起的类似疾病。
• US4985453A
  申请人：——

  公开号：US4985453A

  公开（公告）日：1991-01-15
• US6040326A
  申请人：——

  公开号：US6040326A

  公开（公告）日：2000-03-21