potassium (Z)-1-cyano-3,3,3-trifluoroprop-1-en-2-olate | 2138823-67-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: potassium (Z)-1-cyano-3,3,3-trifluoroprop-1-en-2-olate
• 英文别名: Potassium 1-cyano-3,3,3-trifluoroprop-1-en-2-olate；potassium;(Z)-1-cyano-3,3,3-trifluoroprop-1-en-2-olate
• CAS: 2138823-67-1
• 化学式: C₄HF₃NO*K
• 分子量: 175.152
• InChiKey: WUQSSNNDDIIKLV-SPNQZIMRSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.68
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  46.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-甲苯磺酸酐 、 potassium (Z)-1-cyano-3,3,3-trifluoroprop-1-en-2-olate 以 乙腈 为溶剂， 反应 20.0h， 生成 (Z)-1-cyano-3,3,3-trifluoroprop-1-en-2-yl 4-methylbenzenesulfonate 、 (E)-1-cyano-3,3,3-trifluoroprop-1-en-2-yl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK)

  摘要：

  Increased fructose consumption and its subsequent Metabolism have been implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance in humans. Since ketohexokinase (KHK) is the principal enzyme responsible for fructose metabolism, identification of a selective. KHK inhibitor may help to further elucidate the effect of KHK inhibition on these metabolic disorders. Until now, studies on KHK inhibition with small molecules have been limited due to the lack of viable in vivo pharmacological tools. Herein we report the discovery of 12, a selective KHK inhibitor with potency and properties suitable for evaluating KHK inhibition in rat models. Key structural features interacting with KHK were discovered through fragment-based screening and subsequent optimization using structure-based drug design, and parallel medicinal chemistry led to the identification of pyridine 12.

  DOI：

  10.1021/acs.jmedchem.7b00947
• 作为产物：
  描述：

  三氟乙酸甲酯 、 乙腈 在 potassium tert-butylate 作用下， 以 甲苯 为溶剂， 反应 15.0h， 以80%的产率得到potassium (Z)-1-cyano-3,3,3-trifluoroprop-1-en-2-olate
  参考文献：
  名称：

  磷酸钠共转运蛋白NaPi2a（SLC34A1）的口服生物利用选择性抑制剂的发现。

  摘要：

  磷酸钠共转运蛋白2a或NaPi2a（SLC34A1）是位于肾近端小管中的溶质载体（SLC）转运蛋白，可重新吸收肾小球滤过的磷酸盐。抑制NaPi2a可能会增强尿中磷酸盐的排泄，并纠正与慢性肾脏疾病，矿物质和骨骼疾病（CKD-MBD）的心血管风险增加相关的适应不良的矿物质和激素紊乱。迄今为止，仅描述了非选择性NaPi抑制剂。在这里，我们详细介绍了第一批选择性NaPi2a抑制剂的发现，该发现是由于高通量筛选命中率的优化而产生的。啮齿类动物抑制剂PF-06869206（6f）的口服PK谱可探索选择性NaPi2a抑制的药理作用。

  DOI：

  10.1021/acsmedchemlett.8b00013

文献信息

• Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK)
  作者：Kim Huard、Kay Ahn、Paul Amor、David A. Beebe、Kris A. Borzilleri、Boris A. Chrunyk、Steven B. Coffey、Yang Cong、Edward L. Conn、Jeffrey S. Culp、Matthew S. Dowling、Matthew F. Gorgoglione、Jemy A. Gutierrez、John D. Knafels、Erik A. Lachapelle、Jayvardhan Pandit、Kevin D. Parris、Sylvie Perez、Jeffrey A. Pfefferkorn、David A. Price、Brian Raymer、Trenton T. Ross、Andre Shavnya、Aaron C. Smith、Timothy A. Subashi、Gregory J. Tesz、Benjamin A. Thuma、Meihua Tu、John D. Weaver、Yan Weng、Jane M. Withka、Gang Xing、Thomas V. Magee

  DOI：10.1021/acs.jmedchem.7b00947

  日期：2017.9.28

  Increased fructose consumption and its subsequent Metabolism have been implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance in humans. Since ketohexokinase (KHK) is the principal enzyme responsible for fructose metabolism, identification of a selective. KHK inhibitor may help to further elucidate the effect of KHK inhibition on these metabolic disorders. Until now, studies on KHK inhibition with small molecules have been limited due to the lack of viable in vivo pharmacological tools. Herein we report the discovery of 12, a selective KHK inhibitor with potency and properties suitable for evaluating KHK inhibition in rat models. Key structural features interacting with KHK were discovered through fragment-based screening and subsequent optimization using structure-based drug design, and parallel medicinal chemistry led to the identification of pyridine 12.
• Discovery of Orally Bioavailable Selective Inhibitors of the Sodium-Phosphate Cotransporter NaPi2a (SLC34A1)
  作者：Kevin J. Filipski、Matthew F. Sammons、Samit K. Bhattacharya、Jane Panteleev、Janice A. Brown、Paula M. Loria、Markus Boehm、Aaron C. Smith、Andre Shavnya、Edward L. Conn、Kun Song、Yan Weng、Carie Facemire、Harald Jüppner、Valerie Clerin

  DOI：10.1021/acsmedchemlett.8b00013

  日期：2018.5.10

  NaPi2a may enhance urinary phosphate excretion and correct maladaptive mineral and hormonal derangements associated with increased cardiovascular risk in chronic kidney disease-mineral and bone disorder (CKD-MBD). To date, only nonselective NaPi inhibitors have been described. Herein, we detail the discovery of the first series of selective NaPi2a inhibitors, resulting from optimization of a high-throughput

  磷酸钠共转运蛋白2a或NaPi2a（SLC34A1）是位于肾近端小管中的溶质载体（SLC）转运蛋白，可重新吸收肾小球滤过的磷酸盐。抑制NaPi2a可能会增强尿中磷酸盐的排泄，并纠正与慢性肾脏疾病，矿物质和骨骼疾病（CKD-MBD）的心血管风险增加相关的适应不良的矿物质和激素紊乱。迄今为止，仅描述了非选择性NaPi抑制剂。在这里，我们详细介绍了第一批选择性NaPi2a抑制剂的发现，该发现是由于高通量筛选命中率的优化而产生的。啮齿类动物抑制剂PF-06869206（6f）的口服PK谱可探索选择性NaPi2a抑制的药理作用。