3-(3,4-dihydro-2,4-dioxoquinazolin-1(2H)-yl)propanoic acid | 148673-98-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-(3,4-dihydro-2,4-dioxoquinazolin-1(2H)-yl)propanoic acid
• 英文别名: 3-(2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)propanoic acid；3-(2,4-dioxoquinazolin-1-yl)propanoic acid
• CAS: 148673-98-7
• 化学式: C₁₁H₁₀N₂O₄
• mdl: MFCD01038809
• 分子量: 234.211
• InChiKey: JVMIILRABUCELC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3,4-dihydro-2,4-dioxoquinazolin-1(2H)-yl)propanoic acid 在 磷酸 、 phosphorus pentoxide 作用下， 反应 4.0h， 以82%的产率得到1H,5H-pyrido[3,2,1-ij]quinazoline-1,3,7(2H,6H)-trione
  参考文献：
  名称：

  Synthesis of derivatives of 1-(2-carboxyethyl)-(1H,3H)-quinazoline-2,4-dione

  摘要：

  DOI：

  10.1007/bf02290754
• 作为产物：
  描述：

  2-氨基苯甲酸乙酯 在 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 20.0h， 生成 3-(3,4-dihydro-2,4-dioxoquinazolin-1(2H)-yl)propanoic acid
  参考文献：
  名称：

  1-取代的二氢嘧啶酮和喹唑啉酮衍生物的合成

  摘要：

  DOI：

  10.1007/bf00529585

文献信息

• A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors of NAD⁺-Dependent Enzymes
  作者：Lik Hang Yuen、Srikanta Dana、Yu Liu、Samuel I. Bloom、Ann-Gerd Thorsell、Dario Neri、Anthony J. Donato、Dmitri Kireev、Herwig Schüler、Raphael M. Franzini

  DOI：10.1021/jacs.8b08039

  日期：2019.4.3

  synthesis of inhibitors for several enzymes including PARP15 and SIRT6. The high dissimilarity of NADEL screening fingerprints for different proteins translated into inhibitors that showed selectivity for their target. The discovery of patterns of enriched structures for six out of eight tested proteins is remarkable for a library of 58 302 DNA-tagged structures and illustrates the prospect of focused DNA-encoded

  DNA 编码的化学文库越来越多地用于药物研究，因为它们能够快速发现合成蛋白质配体。在这里，我们探讨了以目标类别为重点的 DNA 编码化学文库是否可以成为实现一系列蛋白质稳健筛选效率的经济高效的工具。该研究表明，为 NAD+ 结合口袋 (NADEL) 设计的 DNA 编码文库有效地对具有 ADP-核糖基转移酶活性的酶的化学结合空间进行采样。提取的信息指导合成多种酶的抑制剂，包括 PARP15 和 SIRT6。不同蛋白质的 NADEL 筛选指纹的高度相似性转化为抑制剂，对其靶标显示出选择性。
• Correction to “A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors of NAD⁺-Dependent Enzymes”
  作者：Lik Hang Yuen、Srikanta Dana、Yu Liu、Samuel I. Bloom、Ann-Gerd Thorsell、Dario Neri、Anthony J. Donato、Dmitri Kireev、Herwig Schüler、Raphael M. Franzini

  DOI：10.1021/jacs.1c06352

  日期：2021.7.28

  investigate this issue, we recorded a series of NMR spectra with A11 purchased from Fluorochem (catalog no. 313748, lot 2; Figures S19–S23 in the updated Supporting Information). The 1H NMR spectrum of A11 was the same as that obtained for the reference compound A108 (enamine, catalog no. EN300-23945; Figure S24 in the Supporting Information). In the HMBC spectra (Figure S23 in the Supporting Information)

  在我们的 DNA 编码化学库中出现的先导结构的合成和评估过程中，我们注意到含有构建块 2-(2,4-dioxotetrahydropyrimidin-1(2 H )-yl)benzoic acid（在手稿中缩写为 A11）的化合物) 显示出与含有结构单元 3-(2,4-dioxo-1,2,3,4-四氢喹唑啉-1-基)丙酸（手稿中缩写为 A108；结构如图 1 所示）的化合物相同的 NMR 谱. 为了研究这个问题，我们使用从 Fluorochem 购买的 A11 记录了一系列 NMR 光谱（目录号 313748，批次 2；更新的支持信息中的图 S19-S23）。在1A11 的 H NMR 光谱与参考化合物 A108 获得的相同（烯胺，目录号 EN300-23945；支持信息中的图 S24）。在 HMBC 光谱中（支持信息中的图 S23），羧酸基团的碳没有显示出与芳香族 C-H 质子的偶联，表明该化合物是
• Combining pharmacophore models derived from DNA-encoded chemical libraries with structure-based exploration to predict Tankyrase 1 inhibitors
  作者：Alba L. Montoya、Marta Glavatskikh、Brayden J. Halverson、Lik Hang Yuen、Herwig Schüler、Dmitri Kireev、Raphael M. Franzini

  DOI：10.1016/j.ejmech.2022.114980

  日期：2023.1

  DNA-encoded chemical libraries (DECLs) interrogate the interactions of a target of interest with vast numbers of molecules. DECLs hence provide abundant information about the chemical ligand space for therapeutic targets, and there is considerable interest in methods for exploiting DECL screening data to predict novel ligands. Here we introduce one such approach and demonstrate its feasibility using

  DNA 编码化学库 (DECL) 询问感兴趣的靶标与大量分子的相互作用。因此，DECL 提供了有关治疗靶点的化学配体空间的丰富信息，并且人们对利用 DECL 筛选数据来预测新配体的方法非常感兴趣。在这里，我们介绍了一种这样的方法，并使用癌症相关的聚（ADP-核糖）转移酶坦科聚合酶 1 (TNKS1) 作为模型靶标证明了其可行性。首先，DECL 亲和力选择产生了结构多样的高效 TNKS1 抑制剂，包括 IC 50值为 0.8 nM 的化合物2 。此外，来自四个 DECL 的 TNKS1 命中被转化为药效团模型，与基于对接的筛选相结合，在市售化合物数据库中识别 TNKS1 配体候选物。这种计算策略提供了位于 DECL 覆盖的化学空间之外的 TNKS1 抑制剂，并产生了 IC 50值为 22 nM 的药物样先导化合物12 。该研究进一步深入了解了筛选数据的可靠性以及文库设计对命中化合物的影响。特别是，该研究表明，虽然一般来说
• [EN] DNA-ENCODED CHEMICAL LIBRARIES<br/>[FR] BIBLIOTHÈQUES DE PRODUITS CHIMIQUES CODÉS PAR ADN
  申请人：PHILOCHEM AG

  公开号：WO2009077173A2

  公开（公告）日：2009-06-25

  A method of preparing a DNA-encoded chemical library comprising members which comprise a chemical moiety, a linking moiety and a DNA moiety, comprising for each member the steps of: (I) coupling a initial building block to a initial coding single strand oligomer via a linking moiety to form a initial conjugate, the initial coding single strand oligomer comprising a first primer region, an initial coding region and a first annealing region; (II) optionally coupling a middle building block and middle coding single strand oligomer to said initial conjugate to form a middle conjugate, the coupling take place in either order, wherein: (a) the middle building block is coupled to the residue of the initial building block; and (b) the middle coding single strand oligomer comprises a middle coding region and second annealing region, and is coupled by: (i) annealing a complementary single strand oligomer which comprises a chemical modifier, a complementary first annealing region, a complementary middle coding region and a complementary second annealing region by interaction between the first annealing region and the complementary first annealing region; (ii) treating the conjugate formed with a DNA polymerase to elongate the initial coding single strand oligomer to be complementary to the complementary middle coding region and the complementary second annealing region; (iii) removing the complementary single strand oligomer by denaturing the DNA and capturing the complementary single strand oligomer via the chemical modifier; (III) coupling a final building block and final coding single strand oligomer to the initial or middle conjugate as appropriate to form a final conjugate, the coupling take place in either order, wherein: (a) the final building block is coupled to the residue of the initial building block, or may be additionally or alternatively be coupled to the residue of the middle building block (if present); and (b) the final coding single strand oligomer comprises a final coding region and a second primer region, and is coupled by: (i) annealing a complementary single strand oligomer which comprises a complementary first or second annealing region as appropriate, a complementary final coding region and a complementary second primer region, by interaction between the first or second annealing region and the complementary first or second annealing region, as appropriate; (ii) treating the conjugate formed with a DNA polymerase to elongate the initial coding single strand oligomer to be complementary to the complementary final coding region and the complementary second primer region, and to elongate the complementary coding strand to be complementary to the initial coding single strand oligomer.
• Synthesis of 1-substituted dihydropyrimidinone and quinazolinone derivatives
  作者：V. Yu. Mitskyavichyus、R. S. Baltrushis

  DOI：10.1007/bf00529585

  日期：1992.10