2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-one | 1356354-06-7

• 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: 2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-one
• 英文别名: 2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-3,4-dihydrothieno[3,4-d]pyrimidin-4(1H)-one；2-sulfanylidene-3-[4-(2,2,2-trifluoroethoxy)phenyl]-1H-thieno[3,4-d]pyrimidin-4-one
• CAS: 1356354-06-7
• 化学式: C₁₄H₉F₃N₂O₂S₂
• 分子量: 358.365
• InChiKey: ZSTGWQUTQQUBOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-one 在 盐酸 、 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 33.0h， 生成 N-[2-[[3,4-二氢-4-氧代-3-[4-(2,2,2-三氟乙氧基)苯基]噻吩并[3,4-d]嘧啶-2-基]硫基]乙基]乙酰胺
  参考文献：
  名称：

  T-3364366 Targets the Desaturase Domain of Delta-5 Desaturase with Nanomolar Potency and a Multihour Residence Time

  摘要：

  Delta-5 desaturase (D5D) catalyzes the conversion from dihomo-gamma linoleic acid (DGLA) to arachidonic acid (AA). DGLA and AA are common precursors of anti- and pro-inflammatory eicosanoids, respectively, making D5D an attractive drug target for inflammatory-related diseases. Despite several reports on D5D inhibitors, their biochemical mechanisms of action (MOAs) remain poorly understood, primarily due to the difficulty in performing quantitative enzymatic analysis. Herein, we report a radio-ligand binding assay to overcome this challenge and characterized T-3364366, a thienopyrimidinone D5D inhibitor, by use of the assay. T-3364366 is a reversible, slow-binding inhibitor with a dissociation half-life in excess of 2.0 h. The long residence time was confirmed in cellular washout assays. Domain swapping experiments between D5D and D6D support [H-3]T-3364366 binding to the desaturase domain of D5D. The present study is the first to demonstrate biochemical MOA of desaturase inhibitors, providing important insight into drug discovery of desaturase enzymes.

  DOI：

  10.1021/acsmedchemlett.6b00241
• 作为产物：
  描述：

  4-(2,2,2-三氟乙氧基)硝基苯 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 25.17h， 生成 2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-one
  参考文献：
  名称：

  FUSED HETEROCYCLIC COMPOUND AND APPLICATION THEREOF

  摘要：

  本发明提供了一种化合物，用于预防或治疗与前列腺素相关的疾病，如动脉粥样硬化、动脉血栓形成、糖尿病、肥胖、哮喘、发热、疼痛、癌症、风湿病、骨关节炎、特应性皮炎等，并具有优越的药理作用、理化性质等。本发明涉及一种由以下式表示的化合物：其中每个符号如规范中定义的那样，或其盐。

  公开号：

  US20130131050A1

文献信息

• Substituted pyrido[2,3-d]pyrimidines as delta-5-desaturase inhibitors
  申请人：Matsunaga Nobuyuki

  公开号：US09023858B2

  公开（公告）日：2015-05-05

  The present invention provides a compound useful for the prophylaxis or treatment of eicosanoid-associated diseases such as atherosclerosis, atherothrombosis, diabetes, obesity, asthma, fever, pain, cancer, rheumatism, osteoarthritis, atopic dermatitis and the like, and having superior pharmacological action, physicochemical properties and the like. The present invention relates to a compound represented by the following formula: wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供了一种化合物，用于预防或治疗与前列腺素相关的疾病，如动脉粥样硬化、动脉血栓形成、糖尿病、肥胖症、哮喘、发热、疼痛、癌症、风湿病、骨关节炎、特应性皮炎等，具有优越的药理作用、物理化学性质等。本发明涉及一种化合物，其表示如下式：其中每个符号如规范中所定义，或其盐。
• US9023858B2
  申请人：——

  公开号：US9023858B2

  公开（公告）日：2015-05-05
• FUSED HETEROCYCLIC COMPOUND AND APPLICATION THEREOF
  申请人：Matsunaga Nobuyuki

  公开号：US20130131050A1

  公开（公告）日：2013-05-23

  The present invention provides a compound useful for the prophylaxis or treatment of eicosanoid-associated diseases such as atherosclerosis, atherothrombosis, diabetes, obesity, asthma, fever, pain, cancer, rheumatism, osteoarthritis, atopic dermatitis and the like, and having superior pharmacological action, physicochemical properties and the like. The present invention relates to a compound represented by the following formula: wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供了一种化合物，用于预防或治疗与前列腺素相关的疾病，如动脉粥样硬化、动脉血栓形成、糖尿病、肥胖、哮喘、发热、疼痛、癌症、风湿病、骨关节炎、特应性皮炎等，并具有优越的药理作用、理化性质等。本发明涉及一种由以下式表示的化合物：其中每个符号如规范中定义的那样，或其盐。
• T-3364366 Targets the Desaturase Domain of Delta-5 Desaturase with Nanomolar Potency and a Multihour Residence Time
  作者：Ikuo Miyahisa、Hideo Suzuki、Atsushi Mizukami、Yukiya Tanaka、Midori Ono、Mark S. Hixon、Junji Matsui

  DOI：10.1021/acsmedchemlett.6b00241

  日期：2016.9.8

  Delta-5 desaturase (D5D) catalyzes the conversion from dihomo-gamma linoleic acid (DGLA) to arachidonic acid (AA). DGLA and AA are common precursors of anti- and pro-inflammatory eicosanoids, respectively, making D5D an attractive drug target for inflammatory-related diseases. Despite several reports on D5D inhibitors, their biochemical mechanisms of action (MOAs) remain poorly understood, primarily due to the difficulty in performing quantitative enzymatic analysis. Herein, we report a radio-ligand binding assay to overcome this challenge and characterized T-3364366, a thienopyrimidinone D5D inhibitor, by use of the assay. T-3364366 is a reversible, slow-binding inhibitor with a dissociation half-life in excess of 2.0 h. The long residence time was confirmed in cellular washout assays. Domain swapping experiments between D5D and D6D support [H-3]T-3364366 binding to the desaturase domain of D5D. The present study is the first to demonstrate biochemical MOA of desaturase inhibitors, providing important insight into drug discovery of desaturase enzymes.