(2S,3R)-2,3-dihydroxy-succinic acid bis(2,5-dioxo-pyrrolidin-1-yl) ester | 61876-55-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: (2S,3R)-2,3-dihydroxy-succinic acid bis(2,5-dioxo-pyrrolidin-1-yl) ester
• 英文别名: bis(2,5-dioxopyrrolidin-1-yl) (2S,3S)-2,3-dihydroxybutanedioate
• CAS: 61876-55-9
• 化学式: C₁₂H₁₂N₂O₁₀
• 分子量: 344.235
• InChiKey: NXVYSVARUKNFNF-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  168
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2S,3R)-2,3-dihydroxy-succinic acid bis(2,5-dioxo-pyrrolidin-1-yl) ester 、 N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.67h， 以73%的产率得到(2R,3R)-N₁,N₄-bis(2-(2-(2-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide
  参考文献：
  名称：

  Tenapanor 的发现：肠 Na+/H+ 交换异构体 3 的一流微系统抑制剂

  摘要：

  我们在此介绍了肠道限制性 Na + /H +交换异构体 3 (NHE3)抑制剂的设计、合成和优化。NHE3 主要在肾脏和胃肠道中表达，在那里它充当主要的吸收性钠转运蛋白。我们需要最低限度的全身性药物，可以阻止胃肠道中钠的吸收，但避免暴露在肾脏中。从相对低效的高生物利用度的命中化合物 ( 1 ) 开始，设计了有效且吸收最少的 NHE3 抑制剂，最终发现了替那帕诺 ( 28 )。Tenapanor 已被美国食品和药物管理局 (FDA) 批准用于治疗成人便秘型肠易激综合征。

  DOI：

  10.1021/acsmedchemlett.2c00037
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 D-酒石酸 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 以70%的产率得到(2S,3R)-2,3-dihydroxy-succinic acid bis(2,5-dioxo-pyrrolidin-1-yl) ester
  参考文献：
  名称：

  Original preparation of conjugates for antibody production against Amicoumacin-related anti-microbial agents

  摘要：

  Amicoumacins are natural products with potent anti-ulcerogenic and anti-bacterial activities, and have been isolated from different Bacillus genera. They belong to a family of 3,4-dihydroisocoumarin derivatives bearing hydroxylated amino acid side chains. The 3,4-dihydroisocoumarin moiety of Amicoumacins has been obtained in two steps from 2-methoxybenzoic acid by combining directed and benzylic metalation strategies. The use of s-BuLi in both steps gave satisfactory and reproducible yields. For the development of an immunoassay (ELISA) of Amicoumacin-related compounds in biological media, the deprotected 3,4-dihydroisocoumarin moiety has been coupled to the BSA carrier protein via a homo-bifunctional linker deriving from D-tartaric acid. This approach enabled to introduce the hydroxylated portion of Amicoumacin directly during the preparation of hapten-protein conjugates. The coupling ratio was evaluated by mass spectrometry. The hapten-protein conjugate showing the best coupling ratio was used to generate polyclonal immunosera in rabbits. After immunoserum titration, ELISA conditions were set up and specificity tests were performed on solutions of pure parent compounds, semi-purified Amicoumacin B as well as on culture supernatants of strains known for their Amicoumacin production. This immunoassay is suitable for a rapid and simple screening test for the production of Amicoumacins and its related compounds by bacterial strains. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.017

文献信息

• Original preparation of conjugates for antibody production against Amicoumacin-related anti-microbial agents
  作者：Svitlana Shinkaruk、Bernard Bennetau、Pierre Babin、Jean-Marie Schmitter、Valerie Lamothe、Catherine Bennetau-Pelissero、Maria C. Urdaci

  DOI：10.1016/j.bmc.2008.08.017

  日期：2008.10

  Amicoumacins are natural products with potent anti-ulcerogenic and anti-bacterial activities, and have been isolated from different Bacillus genera. They belong to a family of 3,4-dihydroisocoumarin derivatives bearing hydroxylated amino acid side chains. The 3,4-dihydroisocoumarin moiety of Amicoumacins has been obtained in two steps from 2-methoxybenzoic acid by combining directed and benzylic metalation strategies. The use of s-BuLi in both steps gave satisfactory and reproducible yields. For the development of an immunoassay (ELISA) of Amicoumacin-related compounds in biological media, the deprotected 3,4-dihydroisocoumarin moiety has been coupled to the BSA carrier protein via a homo-bifunctional linker deriving from D-tartaric acid. This approach enabled to introduce the hydroxylated portion of Amicoumacin directly during the preparation of hapten-protein conjugates. The coupling ratio was evaluated by mass spectrometry. The hapten-protein conjugate showing the best coupling ratio was used to generate polyclonal immunosera in rabbits. After immunoserum titration, ELISA conditions were set up and specificity tests were performed on solutions of pure parent compounds, semi-purified Amicoumacin B as well as on culture supernatants of strains known for their Amicoumacin production. This immunoassay is suitable for a rapid and simple screening test for the production of Amicoumacins and its related compounds by bacterial strains. (c) 2008 Elsevier Ltd. All rights reserved.
• Discovery of Tenapanor: A First-in-Class Minimally Systemic Inhibitor of Intestinal Na⁺/H⁺ Exchanger Isoform 3
  作者：Jeffrey W. Jacobs、Michael R. Leadbetter、Noah Bell、Samantha Koo-McCoy、Christopher W. Carreras、Limin He、Jill Kohler、Kenji Kozuka、Eric D. Labonté、Marc Navre、Andrew G. Spencer、Dominique Charmot

  DOI：10.1021/acsmedchemlett.2c00037

  日期：2022.7.14

  We present herein the design, synthesis, and optimization of gut-restricted inhibitors of Na+/H+ exchanger isoform 3 (NHE3). NHE3 is predominantly expressed in the kidney and gastrointestinal tract where it acts as the major absorptive sodium transporter. We desired minimally systemic agents that would block sodium absorption in the gastrointestinal tract but avoid exposure in the kidney. Starting

  我们在此介绍了肠道限制性 Na + /H +交换异构体 3 (NHE3)抑制剂的设计、合成和优化。NHE3 主要在肾脏和胃肠道中表达，在那里它充当主要的吸收性钠转运蛋白。我们需要最低限度的全身性药物，可以阻止胃肠道中钠的吸收，但避免暴露在肾脏中。从相对低效的高生物利用度的命中化合物 ( 1 ) 开始，设计了有效且吸收最少的 NHE3 抑制剂，最终发现了替那帕诺 ( 28 )。Tenapanor 已被美国食品和药物管理局 (FDA) 批准用于治疗成人便秘型肠易激综合征。