2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-3H-thiopyrano[3,2-d]pyrimidin-4(6H)-one | 1450790-46-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: 2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-3H-thiopyrano[3,2-d]pyrimidin-4(6H)-one
• 英文别名: 2-(4-(Trifluoromethyl)phenyl)-7,8-dihydro-3H-thiopyrano[3,2-D]pyrimidin-4(6H)-one；2-[4-(trifluoromethyl)phenyl]-3,6,7,8-tetrahydrothiopyrano[3,2-d]pyrimidin-4-one
• CAS: 1450790-46-1
• 化学式: C₁₄H₁₁F₃N₂OS
• 分子量: 312.315
• InChiKey: BTCPLJSFXYRLAO-UHFFFAOYSA-N

物化性质

• 沸点：
  410.5±55.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-[(2-乙氧基-2-氧代乙基)硫代]丁酸乙酯 在 sodium hydride 、 potassium carbonate 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 5.0h， 生成 2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-3H-thiopyrano[3,2-d]pyrimidin-4(6H)-one
  参考文献：
  名称：

  Identification of NVP-TNKS656: The Use of Structure–Efficiency Relationships To Generate a Highly Potent, Selective, and Orally Active Tankyrase Inhibitor

  摘要：

  Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, there has been intense interest in developing agents suitable for modulating the Wnt pathway in vivo by targeting this enzyme pair. By utilizing a combination of structure-based design and LipE-based structure efficiency relationships, the core of XAV939 was optimized into a more stable, more efficient, but less potent dihydropyran motif 7. This core was combined with elements of screening hits 2, 19, and 33 and resulted in highly potent, selective tankyrase inhibitors that are novel three pocket binders. NVP-TNKS656 (43) was identified as an orally active antagonist of Wnt pathway activity in the MMTV-Wnt1 mouse xenograft model. With an enthalpy-driven thermodynamic signature of binding, highly favorable physicochemical properties, and high lipophilic efficiency, NVP-TNKS656 is a novel tankyrase inhibitor that is well suited for further in vivo validation studies.

  DOI：

  10.1021/jm400807n

文献信息

• Identification of NVP-TNKS656: The Use of Structure–Efficiency Relationships To Generate a Highly Potent, Selective, and Orally Active Tankyrase Inhibitor
  作者：Michael D. Shultz、Atwood K. Cheung、Christina A. Kirby、Brant Firestone、Jianmei Fan、Christine Hiu-Tung Chen、Zhouliang Chen、Donovan N. Chin、Lucian DiPietro、Aleem Fazal、Yun Feng、Pascal D. Fortin、Ty Gould、Bharat Lagu、Huangshu Lei、Francois Lenoir、Dyuti Majumdar、Etienne Ochala、M. G. Palermo、Ly Pham、Minying Pu、Troy Smith、Travis Stams、Ronald C. Tomlinson、B. Barry Touré、Michael Visser、Run Ming Wang、Nigel J. Waters、Wenlin Shao

  DOI：10.1021/jm400807n

  日期：2013.8.22

  Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, there has been intense interest in developing agents suitable for modulating the Wnt pathway in vivo by targeting this enzyme pair. By utilizing a combination of structure-based design and LipE-based structure efficiency relationships, the core of XAV939 was optimized into a more stable, more efficient, but less potent dihydropyran motif 7. This core was combined with elements of screening hits 2, 19, and 33 and resulted in highly potent, selective tankyrase inhibitors that are novel three pocket binders. NVP-TNKS656 (43) was identified as an orally active antagonist of Wnt pathway activity in the MMTV-Wnt1 mouse xenograft model. With an enthalpy-driven thermodynamic signature of binding, highly favorable physicochemical properties, and high lipophilic efficiency, NVP-TNKS656 is a novel tankyrase inhibitor that is well suited for further in vivo validation studies.