Potassium;(2-acetamido-1,3-benzoxazol-6-yl)-trifluoroboranuide | 1313514-70-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: Potassium;(2-acetamido-1,3-benzoxazol-6-yl)-trifluoroboranuide
• CAS: 1313514-70-3
• 化学式: C₉H₇BF₃N₂O₂*K
• 分子量: 282.071
• InChiKey: YFRGOGMINDFAFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.16
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide 、 Potassium;(2-acetamido-1,3-benzoxazol-6-yl)-trifluoroboranuide 、 三氟乙酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 0.17h， 以11%的产率得到N-(6-(6-chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)benzo[d]oxazol-2-yl)acetamide trifluoroacetate
  参考文献：
  名称：

  Structure–Activity Relationships of Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Investigations of Various 6,5-Heterocycles to Improve Metabolic Stability

  摘要：

  N-(6-(6-Chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)acetamide (1) is a potent and efficacious inhibitor of PI3K alpha and mTOR in vitro and in vivo. However, in hepatocyte and in vivo metabolism studies, 1 was found to undergo deacetylation on the 2-amino substituent of the benzothiazole. As an approach to reduce or eliminate this metabolic deacetylation, a variety of 6,5-heterocyclic analogues were examined as an alternative to the benzothiazole ring. Imidazopyridazine 10 was found to have similar in vitro potency and in vivo efficacy relative to 1, while only minimal amounts of the corresponding deacetylated metabolite of 10 were observed in hepatocytes.

  DOI：

  10.1021/jm2004442
• 作为产物：
  描述：

  2-氨基苯并噁唑 在 吡啶 、 4-二甲氨基吡啶 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium hydrogen bifluoride 、 溴 、 potassium acetate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 49.5h， 生成 Potassium;(2-acetamido-1,3-benzoxazol-6-yl)-trifluoroboranuide
  参考文献：
  名称：

  Structure–Activity Relationships of Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Investigations of Various 6,5-Heterocycles to Improve Metabolic Stability

  摘要：

  N-(6-(6-Chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)acetamide (1) is a potent and efficacious inhibitor of PI3K alpha and mTOR in vitro and in vivo. However, in hepatocyte and in vivo metabolism studies, 1 was found to undergo deacetylation on the 2-amino substituent of the benzothiazole. As an approach to reduce or eliminate this metabolic deacetylation, a variety of 6,5-heterocyclic analogues were examined as an alternative to the benzothiazole ring. Imidazopyridazine 10 was found to have similar in vitro potency and in vivo efficacy relative to 1, while only minimal amounts of the corresponding deacetylated metabolite of 10 were observed in hepatocytes.

  DOI：

  10.1021/jm2004442

文献信息

• Structure–Activity Relationships of Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Investigations of Various 6,5-Heterocycles to Improve Metabolic Stability
  作者：Markian M. Stec、Kristin L. Andrews、Shon K. Booker、Sean Caenepeel、Daniel J. Freeman、Jian Jiang、Hongyu Liao、John McCarter、Erin L. Mullady、Tisha San Miguel、Raju Subramanian、Nuria Tamayo、Ling Wang、Kevin Yang、Leeanne P. Zalameda、Nancy Zhang、Paul E. Hughes、Mark H. Norman

  DOI：10.1021/jm2004442

  日期：2011.7.28

  N-(6-(6-Chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)acetamide (1) is a potent and efficacious inhibitor of PI3K alpha and mTOR in vitro and in vivo. However, in hepatocyte and in vivo metabolism studies, 1 was found to undergo deacetylation on the 2-amino substituent of the benzothiazole. As an approach to reduce or eliminate this metabolic deacetylation, a variety of 6,5-heterocyclic analogues were examined as an alternative to the benzothiazole ring. Imidazopyridazine 10 was found to have similar in vitro potency and in vivo efficacy relative to 1, while only minimal amounts of the corresponding deacetylated metabolite of 10 were observed in hepatocytes.