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.