(S)-2,5-dihydro-pyrrole-1,2-dicarboxylic acid 1-benzyl ester | 161813-74-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-2,5-dihydro-pyrrole-1,2-dicarboxylic acid 1-benzyl ester
• 英文别名: (2S)-1-phenylmethoxycarbonyl-2,5-dihydropyrrole-2-carboxylic acid
• CAS: 161813-74-7
• 化学式: C₁₃H₁₃NO₄
• 分子量: 247.251
• InChiKey: KEKCCPFMDCADEJ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2,5-dihydro-pyrrole-1,2-dicarboxylic acid 1-benzyl ester 在 抗氧剂300 、 caesium carbonate 、 间氯过氧苯甲酸 、 sodium iodide 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 (2S,3S,4S)-4-fluoro-2-(2-fluoro-3-methylbut-2-enylcarbamoyl)-3-methoxypyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] PYRROLIDINE DERIVATIVES AND THEIR USE AS COMPLEMENT PATHWAY MODULATORS
  [FR] DÉRIVÉS PYRROLIDINE ET LEUR UTILISATION EN TANT QUE MODULATEURS DE LA VOIE DU COMPLÉMENT

  摘要：

  本发明提供了一种化合物（I）的方法，用于制造本发明的化合物，并将其作为因子D抑制剂用于治疗眼科疾病。本发明还提供了一种药理活性剂的组合和一种药物组合物。

  公开号：

  WO2014002052A1
• 作为产物：
  描述：

  (2S,4R)-Cbz-4-甲磺酰氧基脯氨酸甲酯 在 吡啶 、 lithium hydroxide 、 sodium tetrahydroborate 、 双氧水 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 (S)-2,5-dihydro-pyrrole-1,2-dicarboxylic acid 1-benzyl ester
  参考文献：
  名称：

  Synthesis of New Didemnin B Analogs for Investigations of Structure/Biological Activity Relationships

  摘要：

  Modifications were introduced in the side chain of didemnin B to afford several analogs (1f-1j) for biological testing in order to identify the features responsible for the bioactivity of the natural products (1a-1c). To achieve our goal, two changes were made in the proline ring of the beta-turn side chain. Initially, a hydroxyl group was incorporated at the C-4 position of the ring to increase the polar nature of the molecule. Secondly, unsaturation was introduced at C-3 and C-4 to increase the rigidity of the ring and to provide a site for tritiation to follow the drug pathway in biological systems. Improvements were also introduced in the macrocycle construction to produce gram quantities of this unit (1d) for the preparation of the planned analogs. The linear precursor to the macrocycle was oxidized more effectively with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane reagent), and cyclization yields were increased substantially by using a new coupling reagent, pentafluorophenyl diphenylphosphinate (FDPP). (1H-1,2,3-benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and pentafluorophenyl trifluoroacetate were also used to improve other coupling reactions.

  DOI：

  10.1021/jo00097a022

文献信息

• [EN] PYRROLIDINE DERIVATIVES AND THEIR USE AS COMPLEMENT PATHWAY MODULATORS<br/>[FR] DÉRIVÉS DE PYRROLIDINE ET LEUR UTILISATION EN TANT QUE MODULATEURS DES VOIES DU COMPLÉMENT
  申请人：NOVARTIS AG

  公开号：WO2014002057A1

  公开（公告）日：2014-01-03

  The present invention provides a compound of formula I: (I) a method for manufacturing the compounds of the invention, and its therapeutic uses as complement alternative inhibitors for the treatment of ocular diseases. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种化合物，其化学式为I：（I），一种制造本发明化合物的方法，以及其作为眼部疾病治疗的补体替代抑制剂的治疗用途。本发明还提供了一种药理活性剂的组合和一种药物组合物。
• Novel Inhibitors of the Amino Acid Transporters ASCT1 and ASCT2
  申请人：Kavanaugh Michael P.

  公开号：US20130065935A1

  公开（公告）日：2013-03-14

  The invention features compounds and methods relating to novel hydroxy-proline analog inhibitors of the ASCT1 and ASCT2 neutral amino acid transporters. These analogs are potent and selective inhibitors of ASCT2 and ASCT1-mediated amino acid transport as evidenced by significantly reduced glutamine or alanine transport-associated currents or radiolabeled substrate (amino acid) uptake in Xenopus oocytes expressing ASCT2 or ASCT1. Selectivity has been established in the same manner whereby reduced substrate associated current or substrate uptake is unobserved in Xenopus oocytes expressing ATA2, SN1, or EAAT(s) (excitatory amino acid transporter). The compounds and methods of the invention can be used in research or clinical applications (e.g., for the treatment of cancer, microbial infection, or ischemia-related central nervous system injury).

  该发明涉及与ASCT1和ASCT2中性氨基酸转运体的新型羟基脯氨酸类似物抑制剂相关的化合物和方法。这些类似物是ASCT2和ASCT1的有效和选择性抑制剂，表现为在表达ASCT2或ASCT1的Xenopus卵母细胞中，显著降低谷氨酸或丙氨酸转运相关的电流或放射标记底物（氨基酸）的摄取。通过类似的方式建立了选择性，即在表达ATA2、SN1或EAAT(s)（兴奋性氨基酸转运体）的Xenopus卵母细胞中观察不到减少底物相关电流或底物摄取。该发明的化合物和方法可用于研究或临床应用（例如，用于癌症、微生物感染或缺血相关中枢神经系统损伤的治疗）。
• COMPLEMENT PATHWAY MODULATORS AND USES THEREOF
  申请人：Altmann Eva

  公开号：US20150141455A1

  公开（公告）日：2015-05-21

  The present invention provides a compound of formula I: (I) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了化合物I的公式：（I），本发明的化合物制备方法及其治疗用途。本发明还提供了一种药理活性剂的组合和制药组合物。
• Radiolabeled Inhibitors of the Amino Acid Transporters ASCT1 and ASCT2
  申请人：Martinelli Stephanie Lynn

  公开号：US20150056138A1

  公开（公告）日：2015-02-26

  The invention features compounds and methods relating to hydroxy-proline analog inhibitors of the ASCT1 and ASCT2 neutral amino acid transporters useful for diagnostic purposes. These analogs are potent and selective inhibitors of ASCT2 and ASCT1-mediated amino acid transport as evidenced by significantly reduced glutamine or alanine transport-associated currents or radiolabeled substrate (amino acid) uptake in Xenopus oocytes expressing ASCT2 or ASCT1. Selectivity has been established in the same manner whereby reduced substrate associated current or substrate uptake is unobserved in Xenopus oocytes expressing ATA2, SN1, or EAAT(s) (excitatory amino acid transporter). The compounds and methods of the invention include radiolabeled inhibitors that can be used in research or clinical applications (e.g., for the treatment of cancer or ischemia-related central nervous system injury).

  本发明涉及羟基脯氨酸类似物抑制ASCT1和ASCT2中性氨基酸转运蛋白的化合物和方法，用于诊断目的。这些类似物是ASCT2和ASCT1介导的氨基酸转运的有效和选择性抑制剂，证明了通过显著减少谷氨酰胺或丙氨酸转运相关电流或放射性标记底物（氨基酸）在表达ASCT2或ASCT1的Xenopus卵母细胞中的摄取。选择性已通过相同的方式建立，其中在表达ATA2，SN1或EAAT（兴奋性氨基酸转运体）的Xenopus卵母细胞中未观察到减少的底物相关电流或底物摄取。本发明的化合物和方法包括可以用于研究或临床应用的放射性标记抑制剂（例如，用于癌症或缺血相关的中枢神经系统损伤的治疗）。
• PYRROLIDINE DERIVATIVES AND THEIR USE AS COMPLEMENT PATHWAY MODULATORS
  申请人：NOVARTIS AG

  公开号：US20150166578A1

  公开（公告）日：2015-06-18

  The present invention provides a compound of formula (I) a method for manufacturing the compounds of the invention and its therapeutic uses as complement pathway modulators for the treatment of ocular diseases. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种式(I)的化合物，一种制备该化合物的方法及其作为补体途径调节剂用于治疗眼部疾病的治疗用途。本发明还提供了药理活性剂的组合和制药组合物。