2-(pyrrol-1-yl)succinic acid dimethyl ester | 80314-89-2

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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: 2-(pyrrol-1-yl)succinic acid dimethyl ester
• 英文别名: 2-Pyrrol-1-ylsuccinic acid dimethyl ester；dimethyl 2-pyrrol-1-ylbutanedioate
• CAS: 80314-89-2
• 化学式: C₁₀H₁₃NO₄
• 分子量: 211.218
• InChiKey: GUDPYHUUWLXMBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(pyrrol-1-yl)succinic acid dimethyl ester 在 盐酸 、 氨 、 三乙胺 作用下， 以 1,4-二氧六环 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 (1,3-Dioxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazin-4-yl)-acetic acid
  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：

  2,5-二乙氧基四氢呋喃 、 DL-aspartic acid dimethyl ester hydrochloride 在 溶剂黄146 、 三乙胺 作用下， 以90%的产率得到2-(pyrrol-1-yl)succinic acid dimethyl ester
  参考文献：
  名称：

  Structure elucidation and synthesis of (2s)-4-oxo-1-azabicyclo[3.3.0]octa-5,7-diehe-2-carboxylic acid, a new metabolite isolated ercm stheptomyces oliyacbjs

  摘要：

  DOI：

  10.1016/s0040-4039(01)81888-8

文献信息

• COMPOUNDS, COMPOSITIONS AND METHODS OF AGELASTATIN ALKALOIDS
  申请人：Massachusetts Institute of Technology

  公开号：US20150080405A1

  公开（公告）日：2015-03-19

  The present invention, among other things, provides compounds, compositions and methods for treatment of cancer. In some embodiments, the present invention provides methods for treating blood cancer using agelastatin alkaloids.

  本发明提供了治疗癌症的化合物、组合物和方法。在一些实施例中，本发明提供了使用阿吉拉斯塔碱类治疗血液癌症的方法。
• Total synthesis and cytotoxic activities of longamide B, longamide B methyl ester, hanishin, and their analogues
  作者：Deng-Gao Zhao、Yan-Yan Ma、Wei Peng、Ai-Yu Zhou、Yu Zhang、Liugang Ding、Zhiyun Du、Kun Zhang

  DOI：10.1016/j.bmcl.2015.11.069

  日期：2016.1

  The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9-15) were evaluated against human lung adenocarcinoma (A549) and human prostate cancer

  海洋生物碱，长酰胺B（1），长酰胺B甲酯（2），haishin（3）和一系列非天然存在的类似物是从廉价的市售dl-天冬氨酸二甲基酯中高效合成的。评价了这些天然产物（1-3）及其类似物（9-15）对人肺腺癌（A549）和人前列腺癌（PC3）细胞的细胞毒性。这是对这些生物碱在这些癌细胞系中的细胞毒性的首次评估，结果表明类似物15具有与其天然母体化合物（±）-hanishin（3）相当的细胞毒性活性。该研究为进一步开发这些生物碱进行结构修饰提供有用的信息，以开发新型抗肿瘤药。
• 4-ALKYL SUBSTITUTED 3,4-DIHYDROPYRROLO[1,2-a]PYRAZIN-1(2H)-ONE DERIVATIVES AS KINASES INHIBITORS
  申请人：Nerviano Medical Sciences S.r.l.

  公开号：EP2788350B1

  公开（公告）日：2017-12-06
• US9434736B2
  申请人：——

  公开号：US9434736B2

  公开（公告）日：2016-09-06
• Novel, Highly Potent Aldose Reductase Inhibitors:  (<i>R</i>)-(−)-2-(4-Bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-<i>a</i>]pyrazine- 4-spiro-3‘-pyrrolidine-1,2‘,3,5‘-tetrone (AS-3201) and Its Congeners
  作者：Toshiyuki Negoro、Makoto Murata、Shozo Ueda、Buichi Fujitani、Yoshiyuki Ono、Akemi Kuromiya、Masanobu Komiya、Kenji Suzuki、Jun-ichi Matsumoto

  DOI：10.1021/jm9802968

  日期：1998.10.1

  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.