ethyl 4-oxo-3H,4H-thieno[2,3-d]pyrimidine-5-carboxylate | 1353498-44-8

• 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
• 英文名称: ethyl 4-oxo-3H,4H-thieno[2,3-d]pyrimidine-5-carboxylate
• 英文别名: Ethyl 4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-5-carboxylate；ethyl 4-oxo-3H-thieno[2,3-d]pyrimidine-5-carboxylate
• CAS: 1353498-44-8
• 化学式: C₉H₈N₂O₃S
• 分子量: 224.24
• InChiKey: QDKAKAYZDFPCIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  96
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-oxo-3H,4H-thieno[2,3-d]pyrimidine-5-carboxylate 在 titanium(IV) isopropylate 、 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 49.0h， 生成 tert-Butyl 4-[4-({[(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)carbonyl]amino}methyl) benzyl]piperazine-1-carboxylate
  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
• 作为产物：
  描述：

  氰乙酸乙酯 在 sulfur 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 ethyl 4-oxo-3H,4H-thieno[2,3-d]pyrimidine-5-carboxylate
  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

• TETRAZOLE DERIVATIVES AS TRPA1 INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20220112210A1

  公开（公告）日：2022-04-14

  The present disclosure provides certain tetrazole derivatives that are inhibitors of transient receptor potential ankyrin 1 (TRPA1), and are therefore useful for the treatment of diseases treatable by inhibition of TRPA1. Also provided are pharmaceutical compositions containing the same, and processes for preparing said compounds.

  本公开提供了某些四唑衍生物，它们是瞬时受体电位蛋白ANKYRIN 1（TRPA1）的抑制剂，因此可用于治疗可通过抑制TRPA1治疗的疾病。还提供了包含相同化合物的药物组合物以及制备该化合物的过程。
• [EN] 3H,4H-THIENO[2,3-d]PYRIMIDIN-4-ONE DERIVATIVES AS TRPA1 INHIBITORS<br/>[FR] DÉRIVÉS 3H, 4H-THIÉNO [2,3-D] PYRIMIDIN-4-ONE EN TANT QU'INHIBITEURS DE TRPA1
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2022219014A1

  公开（公告）日：2022-10-20

  The present disclosure provides certain 3H,4H-thieno[2,3-d]pyrimidin-4-one derivatives that are inhibitors of transient receptor potential ankyrin 1 (TRPA1), and are therefore useful for the treatment of diseases treatable by inhibition of TRPA1. Also provided are pharmaceutical compositions containing the same, and processes for preparing said compounds.

  本公开提供了某些3H、4H-噻吩[2,3-d]嘧啶-4-酮衍生物，它们是瞬时受体电位ANKYRIN 1（TRPA1）的抑制剂，因此可用于治疗可通过抑制TRPA1治疗的疾病。还提供了含有相同化合物的制药组合物以及制备这些化合物的方法。
• 3H,4H-THIENO[2,3-D]PYRIMIDIN-4-ONE DERIVATIVES AS TRPA1 INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20220340590A1

  公开（公告）日：2022-10-27

  The present disclosure provides certain 3H,4H-thieno[2,3-d]pyrimidin-4-one derivatives that are inhibitors of transient receptor potential ankyrin 1 (TRPA1), and are therefore useful for the treatment of diseases treatable by inhibition of TRPA1. Also provided are pharmaceutical compositions containing the same, and processes for preparing said compounds.
• [EN] TETRAZOLE DERIVATIVES AS TRPA1 INHIBITORS<br/>[FR] DÉRIVÉS DE TÉTRAZOLE EN TANT QU'INHIBITEURS DE TRPA1
  申请人：[en]BOEHRINGER INGELHEIM INTERNATIONAL GMBH

  公开号：WO2022079091A1

  公开（公告）日：2022-04-21

  The present disclosure provides certain tetrazole derivatives that are inhibitors of transient receptor potential ankyrin 1 (TRPA1), and are therefore useful for the treatment of diseases treatable by inhibition of TRPA1. Also provided are pharmaceutical compositions containing the same, and processes for preparing said compounds.
• 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.