benzyl (2S)-4-methyl-2-[[10-[[(2S)-4-methyl-1-oxo-1-phenylmethoxypentan-2-yl]carbamoyl]-2,8-dioxo-1,5,7,11-tetrazatricyclo[7.3.0.03,7]dodeca-3,5,9,11-tetraene-4-carbonyl]amino]pentanoate | 627874-38-8

• 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: benzyl (2S)-4-methyl-2-[[10-[[(2S)-4-methyl-1-oxo-1-phenylmethoxypentan-2-yl]carbamoyl]-2,8-dioxo-1,5,7,11-tetrazatricyclo[7.3.0.03,7]dodeca-3,5,9,11-tetraene-4-carbonyl]amino]pentanoate
• CAS: 627874-38-8
• 化学式: C₃₆H₃₈N₆O₈
• 分子量: 682.733
• InChiKey: UAUHJSGOJHNFRR-UIOOFZCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  50
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  181
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-4-methyl-2-[[10-[[(2S)-4-methyl-1-oxo-1-phenylmethoxypentan-2-yl]carbamoyl]-2,8-dioxo-1,5,7,11-tetrazatricyclo[7.3.0.03,7]dodeca-3,5,9,11-tetraene-4-carbonyl]amino]pentanoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2S)-2-[[5-[2-[[4-[[(1S)-1-carboxy-3-methylbutyl]carbamoyl]-1H-imidazole-5-carbonyl]-ethylamino]ethyl-ethylcarbamoyl]-1H-imidazole-4-carbonyl]amino]-4-methylpentanoic acid
  参考文献：
  名称：

  Synthesis of Symmetric Bis(imidazole-4,5-dicarboxamides) Substituted with Amino Acids

  摘要：

  A series of symmetric bis(imidazole-4,5-dicarboxamides) (bis-I45DCs) were prepared with amino acid esters and a variety of linker groups. The critical pyrazine intermediates, substituted with amino acid esters, were synthesized by stoichiometric control of the amino acid ester, even though primary alkanamines, in comparison, generally offer less selectivity for this reaction. Diamines are added to subsequently react with and open the remaining acyl imidazole bonds in the pyrazine intermediates and thereby yield the bis-I45DCs.

  DOI：

  10.1021/jo049045z
• 作为产物：
  描述：

  4H,9H-diimidazo<1,5-a; 1',5'-d>pyrazine-5,10-dione-1,6-dicarboxylic dichloride 、 L-亮氨酸苄酯盐酸盐(1:1) 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以54%的产率得到benzyl (2S)-4-methyl-2-[[10-[[(2S)-4-methyl-1-oxo-1-phenylmethoxypentan-2-yl]carbamoyl]-2,8-dioxo-1,5,7,11-tetrazatricyclo[7.3.0.03,7]dodeca-3,5,9,11-tetraene-4-carbonyl]amino]pentanoate
  参考文献：
  名称：

  Synthesis of Symmetric Bis(imidazole-4,5-dicarboxamides) Substituted with Amino Acids

  摘要：

  A series of symmetric bis(imidazole-4,5-dicarboxamides) (bis-I45DCs) were prepared with amino acid esters and a variety of linker groups. The critical pyrazine intermediates, substituted with amino acid esters, were synthesized by stoichiometric control of the amino acid ester, even though primary alkanamines, in comparison, generally offer less selectivity for this reaction. Diamines are added to subsequently react with and open the remaining acyl imidazole bonds in the pyrazine intermediates and thereby yield the bis-I45DCs.

  DOI：

  10.1021/jo049045z

文献信息

• Parallel Synthesis of an Imidazole-4,5-dicarboxamide Library Bearing Amino Acid Esters and Alkanamines
  作者：Rosanna Solinas、John DiCesare、Paul Baures

  DOI：10.3390/molecules13123149

  日期：——

  The imidazole-4,5-dicarboxylic acid scaffold is readily derivatized with amino acid esters and alkanamines to afford compounds with intramolecularly hydrogen bonded conformations that mimic substituted purines and therefore are hypothesized to be potential inhibitors of kinases through competitive binding to the ATP site. In this work, a total of 126 dissymmetrically disubstituted imidazole-4,5-dicarboxamides with amino acid ester and alkanamide substituents were prepared by parallel synthesis. The library members were purified by column chromatography on silica gel and the purified compounds characterized by LC-MS with LC detection at 214 nm. A selection of the final compounds was also analyzed by 1H-NMR spectroscopy. The analytically pure final products have been submitted to the Molecular Library Small Molecule Repository (MLSMR) for screening in the Molecular Library Screening Center Network (MLSCN) as part of the NIH Roadmap.

  咪唑-4,5-二羧酸骨架易于与氨基酸酯和烷基胺进行衍生化，得到具有分子内氢键的构象类似取代嘌呤的化合物，因此被假设为通过竞争性结合ATP位点成为潜在的激酶抑制剂。在本研究中，通过平行合成法制备了总共126种不对称二取代的咪唑-4,5-二羧酰胺，其取代基为氨基酸酯和烷基酰胺。这些化合物库成员通过硅胶柱层析进行纯化，并采用LC-MS技术在214 nm波长下进行检测，以鉴定纯化后的化合物。部分最终产物还通过1H-NMR光谱进行了分析。这些分析纯的最终产物已提交至分子库小分子数据库（MLSMR），用于在分子库筛选中心网络（MLSCN）中进行筛选，作为NIH路线图计划的一部分。
• Parallel Synthesis of a Library of Symmetrically- and Dissymmetrically-disubstituted Imidazole-4,5-dicarboxamides Bearing Amino Acid Esters
  作者：Rosanna Solinas、John DiCesare、Paul Baures

  DOI：10.3390/molecules14010352

  日期：——

  The imidazole-4,5-dicarboxylic acid scaffold is readily derivatized with amino acid esters to afford symmetrically- and dissymmetrically-disubstituted imidazole-4,5-dicarboxamides with intramolecularly hydrogen bonded conformations that predispose the presentation of amino acid pharmacophores. In this work, a total of 45 imidazole-4,5-dicarboxamides bearing amino acid esters were prepared by parallel synthesis. The library members were purified by column chromatography on silica gel and the purified compounds characterized by LC-MS with LC detection at 214 nm. A selection of the final compounds was also analyzed by 1H-NMR spectroscopy. The analytically pure final products have been submitted to the Molecular Library Small Molecule Repository (MLSMR) for screening in the Molecular Library Screening Center Network (MLSCN) as part of the NIH Roadmap.

  咪唑-4,5-二羧酸骨架可以通过氨基酸酯进行方便的衍生化，从而获得具有内分子氢键构象的对称和不对称二取代咪唑-4,5-二胺，这些构象有利于氨基酸药效团的呈现。在本研究中，通过平行合成制备了共计45种含氨基酸酯的咪唑-4,5-二胺。文库成员通过硅胶柱层析纯化，纯化后的化合物通过LC-MS进行表征，LC检测波长为214 nm。此外，部分最终化合物还通过1H-NMR光谱进行了分析。分析纯的最终产品已提交至分子库小分子库（MLSMR），用于作为NIH路线图的一部分，在分子库筛选中心网络（MLSCN）进行筛选。
• Synthesis of Symmetric Bis(imidazole-4,5-dicarboxamides) Substituted with Amino Acids
  作者：Alexander V. Wiznycia、Jeremy R. Rush、Paul W. Baures

  DOI：10.1021/jo049045z

  日期：2004.11.1

  A series of symmetric bis(imidazole-4,5-dicarboxamides) (bis-I45DCs) were prepared with amino acid esters and a variety of linker groups. The critical pyrazine intermediates, substituted with amino acid esters, were synthesized by stoichiometric control of the amino acid ester, even though primary alkanamines, in comparison, generally offer less selectivity for this reaction. Diamines are added to subsequently react with and open the remaining acyl imidazole bonds in the pyrazine intermediates and thereby yield the bis-I45DCs.
• Parallel Synthesis of An Oligomeric Imidazole-4,5-dicarboxamide Library
  作者：Zhigang Xu、John C. DiCesare、Paul W. Baures

  DOI：10.1021/cc1000105

  日期：2010.3.8

  A library of oligomeric compounds was synthesized based on the imidazole-4,5-dicarboxylic acid scaffold along, with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate nonpolar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala), and were designed to be useful in screening for inhibitors of protein-protein interactions. Many of the protected and deprotected oligomers show evidence of conformational isomers persistent at room temperature in aqueous solution. A total of 317 final oligomers, out of 441 targeted compounds, were obtained in high analytical purity and of sufficient quantity to submit them for high-throughput screening as part of the NIH Roadmap.