3-(3-nitrobenzyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-acetic acid

• 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-(3-nitrobenzyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-acetic acid
• 英文别名: 2-[3-[(3-nitrophenyl)methyl]-2,4-dioxopyrimidin-1-yl]acetic acid
• 化学式: C₁₃H₁₁N₃O₆
• 分子量: 305.247
• InChiKey: HXPSFLFBTMZTJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-硝基溴苄 在 盐酸 、 sodium hydride 、 溶剂黄146 作用下， 反应 7.5h， 生成 3-(3-nitrobenzyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-acetic acid
  参考文献：
  名称：

  Highly Selective Aldose Reductase Inhibitors. 3. Structural Diversity of 3-(Arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic Acids

  摘要：

  Accumulation of intracellular sorbitol, the reduced product of glucose, catalyzed by aldose reductase (AR) (EC 1.1.1.21), is thought to be the cause of the development of diabetic complications. Our attention is focused on finding compounds which inhibit AR without significantly inhibiting aldehyde reductase (ALR) (EC 1.1.1.2). The uracil or 2,4-dioxoimidazolidine skeleton having the benzothiazolyl or 4-chloro-3-nitrophenyl group as an aryl part indicated not only extremely high AR inhibitory activity but also AR selectivity. The ratio of IC50(ALR)/IC50(AR) of 3-[(5-chlorobenzothiazol-2-yl)methyl]-1,2,3,4-tetrahydro-2,4-dioxopyrim-idine-1-acetic acid (47d) was more than 17 500. The uracil skeleton with the benzothiazolyl moiety seemed to be the best combination for selective AR inhibition.

  DOI：

  10.1021/jm960594+
• 作为试剂：
  描述：

  Pyrimidine-1-acetate 、 3-(3-nitrobenzyl)-4,5-dioxo-2-thioxoimidazolidine-1-acetic acid 、 盐酸 、 溶剂黄146 在 溶剂黄146 、 盐酸 、 水 、 乙醇 、 3-(3-nitrobenzyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-acetic acid 作用下， 反应 4.0h， 以to give 1.39 g of 3-(3-nitrobenzyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-acetic acid [Compound 16] as white crystals的产率得到3-(3-nitrobenzyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-acetic acid
  参考文献：
  名称：

  Carboxyalkyl heterocyclic derivatives

  摘要：

  羧基烷基杂环衍生物及其药学上可接受的盐，以及含有该化合物作为有效成分的治疗剂，是用于治疗糖尿病并发症，例如糖尿病神经病变、糖尿病白内障和视网膜病变、糖尿病肾病、糖尿病皮肤病和其他糖尿病微血管病的有用药物。本发明的化合物由以下一般式(A)表示：##STR1## 本发明的化合物表现出对醛糖还原酶的优异抑制作用，具有高酶选择性。因此，它们可用作治疗和预防各种类型的糖尿病并发症的药物，而不会显著抑制醛糖还原酶。

  公开号：

  US05912261A1

文献信息

• US5912261A
  申请人：——

  公开号：US5912261A

  公开（公告）日：1999-06-15
• Highly Selective Aldose Reductase Inhibitors. 3. Structural Diversity of 3-(Arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic Acids
  作者：Takayuki Kotani、Yasuhiro Nagaki、Akira Ishii、Yukari Konishi、Hisashi Yago、Seishi Suehiro、Nobuhisa Okukado、Kaoru Okamoto

  DOI：10.1021/jm960594+

  日期：1997.2.1

  Accumulation of intracellular sorbitol, the reduced product of glucose, catalyzed by aldose reductase (AR) (EC 1.1.1.21), is thought to be the cause of the development of diabetic complications. Our attention is focused on finding compounds which inhibit AR without significantly inhibiting aldehyde reductase (ALR) (EC 1.1.1.2). The uracil or 2,4-dioxoimidazolidine skeleton having the benzothiazolyl or 4-chloro-3-nitrophenyl group as an aryl part indicated not only extremely high AR inhibitory activity but also AR selectivity. The ratio of IC50(ALR)/IC50(AR) of 3-[(5-chlorobenzothiazol-2-yl)methyl]-1,2,3,4-tetrahydro-2,4-dioxopyrim-idine-1-acetic acid (47d) was more than 17 500. The uracil skeleton with the benzothiazolyl moiety seemed to be the best combination for selective AR inhibition.
• Carboxyalkyl heterocyclic derivatives
  申请人：Nippon Zoki Pharmaceutical Co., Ltd.

  公开号：US05912261A1

  公开（公告）日：1999-06-15

  Carboxyalkyl heterocyclic derivatives, pharmaceutically acceptable salts thereof, and therapeutic agents containing said compounds as an effective component are useful pharmaceuticals for the treatment of diabetic complications such as diabetic neuropathy, diabetic cataracts and retinopathy, diabetic nephropathy, diabetic dermopathy, and other diabetic microangiopathy. The compounds of the present invention are represented by the following general formula (A): ##STR1## The compounds of the present invention exhibit excellent inhibitory action towards aldose reductase with a high enzyme selectivity. Accordingly, they are useful as drugs for the therapy and prevention of various types of diabetic complications without substantially inhibiting aldehyde reductase.

  羧基烷基杂环衍生物及其药学上可接受的盐，以及含有该化合物作为有效成分的治疗剂，是用于治疗糖尿病并发症，例如糖尿病神经病变、糖尿病白内障和视网膜病变、糖尿病肾病、糖尿病皮肤病和其他糖尿病微血管病的有用药物。本发明的化合物由以下一般式(A)表示：##STR1## 本发明的化合物表现出对醛糖还原酶的优异抑制作用，具有高酶选择性。因此，它们可用作治疗和预防各种类型的糖尿病并发症的药物，而不会显著抑制醛糖还原酶。