2-oxo-pyrrolidine-1,3-dicarboxylic acid 3-benzyl ester 1-tert-butyl ester | 193264-88-9

• 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: 2-oxo-pyrrolidine-1,3-dicarboxylic acid 3-benzyl ester 1-tert-butyl ester
• 英文别名: 3-benzyl 1-(tert-butyl) 2-oxopyrrolidine-1,3-dicarboxylate；3-O-benzyl 1-O-tert-butyl 2-oxopyrrolidine-1,3-dicarboxylate
• CAS: 193264-88-9
• 化学式: C₁₇H₂₁NO₅
• 分子量: 319.357
• InChiKey: YPBJLHUKCNDOFD-UHFFFAOYSA-N

物化性质

• 沸点：
  464.9±38.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-oxo-pyrrolidine-1,3-dicarboxylic acid 3-benzyl ester 1-tert-butyl ester 在 偶氮二异丁腈 、 quinolinium camphor-10-sulfonate 、 三乙基铝 、 三正丁基氢锡 、 sodium hydride 、 二异丁基氢化铝 、 magnesium 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 25.0h， 生成 2-氧代-1,2-二氢螺[吲哚-3,3-吡咯烷]-1-羧酸叔丁酯
  参考文献：
  名称：

  A convenient route to spiropyrrolidinyl-oxindole alkaloids via C-3 substituted ene-pyrrolidine carbamate radical cyclization

  摘要：

  A short access to spiropyrrolidinyl-oxindole alkaloids via a substituted ene-pyrrolidine carbamate, synthesized from the commercially available tert-butyl 1-pyrrolidine carboxylate, is described. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)00193-2
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 5.0h， 生成 2-oxo-pyrrolidine-1,3-dicarboxylic acid 3-benzyl ester 1-tert-butyl ester
  参考文献：
  名称：

  Discovery and Structure-Based Optimization of Next-Generation Reversible Methionine Aminopeptidase-2 (MetAP-2) Inhibitors

  摘要：

  Co- and post-translational processing are crucial maturation steps to generate functional proteins. MetAP-2 plays an important role in this process, and inhibition of its proteolytic activity has been shown to be important for angiogenesis and tumor growth, suggesting that small-molecule inhibitors of MetAP-2 may be promising options for the treatment of cancer. This work describes the discovery and structure based hit optimization of a novel MetAP-2 inhibitory scaffold. Of critical importance, a cyclic tartronic diamide coordinates the MetAP-2 metal ion in the active site while additional side chains of the molecule were designed to occupy the lipophilic methionine side chain recognition pocket as well as the shallow cavity at the opening of the active site. The racemic screening hit from HTS campaign I la was discovered with an enzymatic IC50 of 150 nM. The resynthesized eutomer confirmed this activity and inhibited HUVEC proliferation with an IC50 of 1.9 mu M. Its structural analysis revealed a sophisticated interaction pattern of polar and lipophilic contacts that were used to improve cellular potency to an IC50 of 15 nM. In parallel, the molecular properties were optimized on plasma exposure and antitumor efficacy which led to the identification of advanced lead 21.

  DOI：

  10.1021/acs.jmedchem.9b00041

文献信息

• 作为TEAD抑制剂的杂环化合物
  申请人：武汉人福创新药物研发中心有限公司

  公开号：CN116332922A

  公开（公告）日：2023-06-27

  本发明提供了一种作为TEAD抑制剂的杂环化合物，所述杂环化合物具有式I所示结构： 式I中各个基团的定义如本发明中所述；所述杂环化合物可用于预防和/或治疗与TEAD表达增加相关的疾病，如细胞增殖性病症疾病。
• Copper-catalysed approach to spirocyclic oxindoles via a direct C–H, Ar-H functionalisation
  作者：Catherine L. Moody、Vilius Franckevičius、Pauline Drouhin、Johannes E.M.N. Klein、Richard J.K. Taylor

  DOI：10.1016/j.tetlet.2012.01.120

  日期：2012.4

  A practical and efficient entry to spirocyclic oxindoles from readily accessible anilide precursors, using only catalytic amounts of an inexpensive copper salt together with air as the sole re-oxidant, is described. In addition to providing access to a broad range of spiro-oxindole products, the utility of this method is demonstrated in a formal synthesis of the natural product, horsfiline. (C) 2012 Elsevier Ltd. All rights reserved.
• A Convenient Procedure for the Conversion Of N-Boc Protected Pyrrolidinone Derivatives Into Their Corresponding Enecarbamates
  作者：Cossy、Cases、Gomez Pardo

  DOI：10.1080/00397919708004150

  日期：1997.8

  When N-Boc protected pyrrolidinone derivatives are treated by Dibal-H and then by quinolinium camphorsulfonate, they are converted into their corresponding enecarbamate.
• A convenient route to spiropyrrolidinyl-oxindole alkaloids via C-3 substituted ene-pyrrolidine carbamate radical cyclization
  作者：Janine Cossy、Manuel Cases、Domingo Gomez Pardo

  DOI：10.1016/s0040-4039(98)00193-2

  日期：1998.4

  A short access to spiropyrrolidinyl-oxindole alkaloids via a substituted ene-pyrrolidine carbamate, synthesized from the commercially available tert-butyl 1-pyrrolidine carboxylate, is described. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Discovery and Structure-Based Optimization of Next-Generation Reversible Methionine Aminopeptidase-2 (MetAP-2) Inhibitors
  作者：Timo Heinrich、Jeyaprakashnarayanan Seenisamy、Beatrix Blume、Jörg Bomke、Michel Calderini、Uwe Eckert、Manja Friese-Hamim、Rainer Kohl、Martin Lehmann、Birgitta Leuthner、Djordje Musil、Felix Rohdich、Frank T. Zenke

  DOI：10.1021/acs.jmedchem.9b00041

  日期：2019.5.23

  Co- and post-translational processing are crucial maturation steps to generate functional proteins. MetAP-2 plays an important role in this process, and inhibition of its proteolytic activity has been shown to be important for angiogenesis and tumor growth, suggesting that small-molecule inhibitors of MetAP-2 may be promising options for the treatment of cancer. This work describes the discovery and structure based hit optimization of a novel MetAP-2 inhibitory scaffold. Of critical importance, a cyclic tartronic diamide coordinates the MetAP-2 metal ion in the active site while additional side chains of the molecule were designed to occupy the lipophilic methionine side chain recognition pocket as well as the shallow cavity at the opening of the active site. The racemic screening hit from HTS campaign I la was discovered with an enzymatic IC50 of 150 nM. The resynthesized eutomer confirmed this activity and inhibited HUVEC proliferation with an IC50 of 1.9 mu M. Its structural analysis revealed a sophisticated interaction pattern of polar and lipophilic contacts that were used to improve cellular potency to an IC50 of 15 nM. In parallel, the molecular properties were optimized on plasma exposure and antitumor efficacy which led to the identification of advanced lead 21.