1,4-二氢-4-氧代噻吩并[2,3-d]嘧啶-5-羧酸 | 1104926-91-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 中文名称: 1,4-二氢-4-氧代噻吩并[2,3-d]嘧啶-5-羧酸
• 英文名称: 4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-5-carboxylic acid
• 英文别名: 4-Oxo-1,4-dihydrothieno[2,3-d]pyrimidine-5-carboxylic acid；4-oxo-3H-thieno[2,3-d]pyrimidine-5-carboxylic acid
• CAS: 1104926-91-1
• 化学式: C₇H₄N₂O₃S
• 分子量: 196.186
• InChiKey: OJNWNTNUJCAOSU-UHFFFAOYSA-N

物化性质

• 密度：
  1.88

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,4-二氢-4-氧代噻吩并[2,3-d]嘧啶-5-羧酸 在 1-丙基磷酸酐 、 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 17.5h， 生成 4-chloro-N-methyl-N-phenylthieno[2,3-d]pyrimidine-5-carboxamide
  参考文献：
  名称：

  The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K)

  摘要：

  我们报告了 PI5P4Kα/γ 双抑制剂的合理设计。ARUK2007145 (39) 是一种强效的细胞活性探针分子，具有适合在细胞中进行实验的 ADMET 特性。

  DOI：

  10.1039/d3md00355h
• 作为产物：
  描述：

  2-氨基-3,4-噻吩羧酸-3-乙基-4-甲酯 在 lithium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 70.0h， 生成 1,4-二氢-4-氧代噻吩并[2,3-d]嘧啶-5-羧酸
  参考文献：
  名称：

  Selective Inhibitors of Bacterial t-RNA-(N¹G37) Methyltransferase (TrmD) That Demonstrate Novel Ordering of the Lid Domain

  摘要：

  The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.

  DOI：

  10.1021/jm400718n

文献信息

• A practical synthesis of 5-functionalized thieno[2,3-d]pyrimidines
  作者：Birgit Wilding、Stefan Faschauner、Norbert Klempier

  DOI：10.1016/j.tetlet.2015.05.104

  日期：2015.7

  The synthesis of 5-hydroxymethyl-, 5-acetoxymethyl-, 5-formyl- and 5-cyanothieno[2,3-d]pyrimidines, the (methyl)-5-carboxylate, and the respective amide functionality was accomplished by building up the functionalized molecule starting from appropriately substituted thiophene precursors. A similar strategy starting from the pyrimidine precursor and subsequent direct functionalization (formylation and cyanation) of the thieno[2,3-d]pyrimidine parent compound in position 5 was found to be less feasible. (C) 2015 Elsevier Ltd. All rights reserved.
• PAPD5 INHIBITORS AND METHODS OF USE THEREOF
  申请人：Children`s Medical Center Corporation

  公开号：US20210177827A1

  公开（公告）日：2021-06-17

  The disclosure relates to compounds that are, e.g., PAP Associated Domain Containing 5 (PAPD5) inhibitors and methods of use thereof.
• Selective Inhibitors of Bacterial t-RNA-(N¹G37) Methyltransferase (TrmD) That Demonstrate Novel Ordering of the Lid Domain
  作者：Pamela J. Hill、Ayome Abibi、Robert Albert、Beth Andrews、Moriah M. Gagnon、Ning Gao、Tyler Grebe、Laurel I. Hajec、Jian Huang、Stephania Livchak、Sushmita D. Lahiri、David C. McKinney、Jason Thresher、Hongming Wang、Nelson Olivier、Ed T. Buurman

  DOI：10.1021/jm400718n

  日期：2013.9.26

  The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.
• The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K)
  作者：Gregory G. Aldred、Timothy P. C. Rooney、Henriette M. G. Willems、Helen K. Boffey、Christopher Green、David Winpenny、John Skidmore、Jonathan H. Clarke、Stephen P. Andrews

  DOI：10.1039/d3md00355h

  日期：——

  We report the rational design of PI5P4Kα/γ dual inhibitors. ARUK2007145 (39) is disclosed as a potent, cell-active probe molecule with ADMET properties amenable to conducting experiments in cells.

  我们报告了 PI5P4Kα/γ 双抑制剂的合理设计。ARUK2007145 (39) 是一种强效的细胞活性探针分子，具有适合在细胞中进行实验的 ADMET 特性。