3-(3-nitrobenzyl)-2,4,5-trioxoimidazolidine-1-acetic acid | 128043-99-2

• 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: 3-(3-nitrobenzyl)-2,4,5-trioxoimidazolidine-1-acetic acid
• 英文别名: NZ-314；3-Carboxymethyl-1-(3-nitrobenzyl)parabanic acid；D77Vnr6rkh；2-[3-[(3-nitrophenyl)methyl]-2,4,5-trioxoimidazolidin-1-yl]acetic acid
• CAS: 128043-99-2
• 化学式: C₁₂H₉N₃O₇
• 分子量: 307.219
• InChiKey: YREIRIKJAMPPHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-硝基苄胺盐酸盐 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 3-(3-nitrobenzyl)-2,4,5-trioxoimidazolidine-1-acetic 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

• Highly Selective Aldose Reductase Inhibitors. II. Optimization of the Aryl Part of 3-(Arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic Acids.
  作者：Takayuki KOTANI、Akira ISHII、Yasuhiro NAGAKI、Yoshio TOYOMAKI、Hisashi YAGO、Seishi SUEHIRO、Nobuhisa OKUKADO、Kaoru OKAMOTO

  DOI：10.1248/cpb.45.297

  日期：——

  Accumulation of intracellular sorbitol, the product of glucose reduction catalyzed by aldose reductase (AR) [EC 1.1.1.21], is thought to be the main culprit in the development of diabetic complications. A series of 3-arylalkyl-2,4,5-trioxoimidazolidine-1-acetic acids was prepared and tested for inhibitory activities towards AR and aldehyde reductase (ALR) [EC 1.1.1.2]. These derivatives showed strong

  醛糖还原酶（AR）[EC 1.1.1.21]催化的葡萄糖还原产物胞内山梨醇的积累被认为是糖尿病并发症发展的主要元凶。制备了一系列3-芳基烷基-2,4,5-三氧代咪唑烷-1-乙酸，并测试了其对AR和醛还原酶（ALR）的抑制活性[EC 1.1.1.2]。这些衍生物显示出对AR的强抑制活性，而没有明显抑制ALR。特别地，具有3-硝基苯基，4-氯-3-硝基苯基和氯取代的苯并噻唑基作为芳基部分的化合物显示出强大的AR抑制活性。氯取代的苯并噻唑基化合物的AR选择性超过5,000倍。
• Parabanic acid derivatives and pharmaceutical compositions thereof
  申请人：Nippon Zoki Pharmaceutical Co., Ltd.

  公开号：US04985453A1

  公开（公告）日：1991-01-15

  Parabanic acid compound of the formula (I): ##STR1## wherein R is hydrogen or a lower alkyl group, X is hydrogen, an alkyl group, a cycloalkyl group, a lower alkylcycloalkyl group, a phenyl group or a phenalkyl group, and n represents an integer of 1 to 4, exhibit excellent aldose reductase inhibitory activity and are useful as drugs for treating or prevention of complications of diabetes.

  化合物Parabanic acid的化学式为(I): ##STR1## 其中R为氢或低碳基，X为氢，烷基，环烷基，低碳基环烷基，苯基或苯基烷基，n表示1至4的整数，具有出色的醛糖还原酶抑制活性，可用作治疗或预防糖尿病并发症的药物。
• 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。
• Medical devices to treat or inhibit restenosis
  申请人：Hezi-Yamit Ayala

  公开号：US20060062822A1

  公开（公告）日：2006-03-23

  Implantable medical devices having anti-restenotic coatings are disclosed. Specifically, implantable medical devices having coatings of aldose reductase (AR) inhibitors are disclosed. Preferred AR inhibitors are enumerated. The anti-restenotic medical devices include stents, catheters, micro-particles, probes and vascular grafts. Intravascular stents are preferred medical devices. The medical devices can be coated using any method known in the art including compounding the AR inhibitor with a biocompatible polymer prior to applying the coating. Moreover, medical devices composed entirely of biocompatible polymer-AR inhibitor blends are disclosed. Additionally, medical devices having a coating comprising at least one AR inhibitor in combination with at least one additional therapeutic agent are also disclosed. Furthermore, related methods of using and making the anti-restenotic implantable devices are also disclosed.

  本研究公开了具有抗血管狭窄涂层的植入式医疗器械。具体而言，公开了具有醛糖还原酶（AR）抑制剂涂层的植入式医疗器械。本文列举了优选的 AR 抑制剂。抗血管再狭窄医疗器械包括支架、导管、微颗粒、探针和血管移植物。血管内支架是首选的医疗器械。这些医疗器械可以使用本领域已知的任何方法进行涂层，包括在涂覆前将 AR 抑制剂与生物相容性聚合物复合。此外，还公开了完全由生物相容性聚合物-AR 抑制剂混合物组成的医疗器械。此外，还公开了具有由至少一种 AR 抑制剂与至少一种额外治疗剂组合而成的涂层的医疗设备。此外，还公开了使用和制造抗再狭窄植入装置的相关方法。