(S)-3-Amino-2,5-dioxo-pyrrolidine-3-carboxylic acid ethyl ester | 1037842-82-2

• 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: (S)-3-Amino-2,5-dioxo-pyrrolidine-3-carboxylic acid ethyl ester
• 英文别名: ethyl (3S)-3-amino-2,5-dioxopyrrolidine-3-carboxylate
• CAS: 1037842-82-2
• 化学式: C₇H₁₀N₂O₄
• 分子量: 186.167
• InChiKey: PJMURKYAHVPDLH-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  98.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-3-Amino-2,5-dioxo-pyrrolidine-3-carboxylic acid ethyl ester 在 溶剂黄146 作用下， 以 氯仿 为溶剂， 反应 17.5h， 生成 (S)-2',5'-Dioxo-2-(2,2,2-trichloro-acetyl)-1',2',4',5'-tetrahydro-[1,3']bipyrrolyl-3'-carboxylic acid ethyl ester
  参考文献：
  名称：

  Novel, Highly Potent Aldose Reductase Inhibitors:  (R)-(−)-2-(4-Bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine- 4-spiro-3‘-pyrrolidine-1,2‘,3,5‘-tetrone (AS-3201) and Its Congeners

  摘要：

  A series of novel tetrahydropyrrolo[1,2-a]pyrazine derivatives were synthesized and evaluated as aldose reductase inhibitors (ARIs) on the basis of their abilities to inhibit porcine lens aldose reductase (AR) in vitro and to inhibit sorbitol accumulation in the sciatic nerve of streptozotocin-induced diabetic rats in vivo. Of these compounds, spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives showed significantly potent AR inhibitory activity. In the in vivo activity of these derivatives, 2-(4-bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo- [1,2-a][1,2a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone (23t) (SX-3030) showed the best oral activity. The enantiomers of 23t were synthesized, and the biological activities were evaluated. It was found that AR inhibitory activity resides in the (-)-enantiomer 43 (AS-3201), which was 10 times more potent in inhibition of the AR (IC50 = 1.5 x 10(-8) M) and 500 times more potent in the in vivo activity (ED50 = 0.18 mg/kg/day for 5 days) than the corresponding (+)enantiomer 44 (SX-3202): From these results, AS-3201 was selected as the candidate for clinical development. The absolute configuration of AS-3201 was also established to be (R)-form by single-crystal X-ray analysis. In this article we report the preparation and structure-activity relationship (SAR) of tetrahydropyrrolopyrazine derivatives including a novel ARI, AS-3201.

  DOI：

  10.1021/jm9802968
• 作为产物：
  描述：

  2-benzyloxycarbonylamino-2-ethoxycarbonyl succinimide 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 40.0~50.0 ℃ 、101.33 kPa 条件下， 生成 (S)-3-Amino-2,5-dioxo-pyrrolidine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Novel, Highly Potent Aldose Reductase Inhibitors:  (R)-(−)-2-(4-Bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine- 4-spiro-3‘-pyrrolidine-1,2‘,3,5‘-tetrone (AS-3201) and Its Congeners

  摘要：

  A series of novel tetrahydropyrrolo[1,2-a]pyrazine derivatives were synthesized and evaluated as aldose reductase inhibitors (ARIs) on the basis of their abilities to inhibit porcine lens aldose reductase (AR) in vitro and to inhibit sorbitol accumulation in the sciatic nerve of streptozotocin-induced diabetic rats in vivo. Of these compounds, spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives showed significantly potent AR inhibitory activity. In the in vivo activity of these derivatives, 2-(4-bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo- [1,2-a][1,2a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone (23t) (SX-3030) showed the best oral activity. The enantiomers of 23t were synthesized, and the biological activities were evaluated. It was found that AR inhibitory activity resides in the (-)-enantiomer 43 (AS-3201), which was 10 times more potent in inhibition of the AR (IC50 = 1.5 x 10(-8) M) and 500 times more potent in the in vivo activity (ED50 = 0.18 mg/kg/day for 5 days) than the corresponding (+)enantiomer 44 (SX-3202): From these results, AS-3201 was selected as the candidate for clinical development. The absolute configuration of AS-3201 was also established to be (R)-form by single-crystal X-ray analysis. In this article we report the preparation and structure-activity relationship (SAR) of tetrahydropyrrolopyrazine derivatives including a novel ARI, AS-3201.

  DOI：

  10.1021/jm9802968

文献信息

• OPTICALLY ACTIVE 3-AMINO-2,5-DIOXOPYRROLIDINE-3-CARBOXYLATE, PROCESS FOR PRODUCTION OF THE COMPOUND, AND USE OF THE COMPOUND
  申请人：Tanaka Daisuke

  公开号：US20120010405A1

  公开（公告）日：2012-01-12

  The present invention provides a compound of the formula (III): wherein R is a C 1-6 alkyl group, as a novel optically active intermediate for preparing tetrahydropyrrolo[1,2-a]pyrazin-4-spiro-3′-pyrrolidine derivatives such as Ranirestat being a promising therapeutic agent for diabetic complications in a short process, in an economically advantageous manner and in high yields, and the process for preparing the same.

  本发明提供了一种公式（III）的化合物： 其中R是C1-6烷基，作为一种新颖的光学活性中间体，用于制备四氢吡咯并[1,2-a]吡嗪-4-螺-3'-吡咯啉衍生物，例如Ranirestat，它是一种有前途的治疗糖尿病并发症的治疗剂，通过一种短工艺、经济优势方式和高产率的方法进行制备。
• US8058456B2
  申请人：——

  公开号：US8058456B2

  公开（公告）日：2011-11-15