| 1310049-09-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 1310049-09-2
• 化学式: C₁₂H₇BrClF₃N₂O₂S
• 分子量: 415.618
• InChiKey: MONRZNXWGZWJHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.32
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  59.06
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  potassium N-(6-(trifluoroboryl)benzo[d]thiazol-2-yl)acetamide 、 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.08h， 以62%的产率得到N-(6-(6-chloro-5-(2-(trifluoromethyl)phenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)acetamide
  参考文献：
  名称：

  Discovery and Optimization of a Series of Benzothiazole Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors

  摘要：

  Phosphoinositide 3-kinase alpha (Pi3K alpha) is a lipid kinase that plays a key regulatory role in several cellular processes. The mutation or amplification of this kinase in humans has been implicated in the growth of multiple tumor types. Consequently, PI3K alpha has become a target of intense research for drug discovery. Our studies began with the identification of benzothiazole compound 1 from a high throughput screen. Extensive SAR studies led to the discovery of sulfonamide 45 as an early lead, based on its in vitro cellular potency. Subsequent modifications of the central pyrimidine ring dramatically improved enzyme and cellular potency and led to the identification of chloropyridine 70. Further arylsulfonamide SAR studies optimized in vitro clearance and led to the identification of 82 as a potent dual inhibitor of PI3K and mTOR This molecule exhibited potent enzyme and cell activity, low clearance, and high oral bioavailability. In addition, compound 82 demonstrated tumor growth inhibition in U-87 MG, A549, and HCT116 tumor xenograft models.

  DOI：

  10.1021/jm1014605
• 作为产物：
  描述：

  2-氯-3-氨基-5-溴吡啶 、 2-三氟甲基苯磺酰氯 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 以45%的产率得到
  参考文献：
  名称：

  Discovery and Optimization of a Series of Benzothiazole Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors

  摘要：

  Phosphoinositide 3-kinase alpha (Pi3K alpha) is a lipid kinase that plays a key regulatory role in several cellular processes. The mutation or amplification of this kinase in humans has been implicated in the growth of multiple tumor types. Consequently, PI3K alpha has become a target of intense research for drug discovery. Our studies began with the identification of benzothiazole compound 1 from a high throughput screen. Extensive SAR studies led to the discovery of sulfonamide 45 as an early lead, based on its in vitro cellular potency. Subsequent modifications of the central pyrimidine ring dramatically improved enzyme and cellular potency and led to the identification of chloropyridine 70. Further arylsulfonamide SAR studies optimized in vitro clearance and led to the identification of 82 as a potent dual inhibitor of PI3K and mTOR This molecule exhibited potent enzyme and cell activity, low clearance, and high oral bioavailability. In addition, compound 82 demonstrated tumor growth inhibition in U-87 MG, A549, and HCT116 tumor xenograft models.

  DOI：

  10.1021/jm1014605