7-Chloro-1-ethyl-6-fluoro-2-methanesulfinyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester | 1082203-80-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-Chloro-1-ethyl-6-fluoro-2-methanesulfinyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
• 英文别名: ethyl 7-chloro-1-ethyl-6-fluoro-2-methylsulfinyl-4-oxoquinoline-3-carboxylate
• CAS: 1082203-80-2
• 化学式: C₁₅H₁₅ClFNO₄S
• 分子量: 359.806
• InChiKey: IQNCWIDCNAJQNI-UHFFFAOYSA-N

物化性质

• 沸点：
  532.3±50.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-Chloro-1-ethyl-6-fluoro-2-methanesulfinyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 在 盐酸羟胺 、 sodium acetate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 C₁₂H₈ClFN₂O₃
  参考文献：
  名称：

  Isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones as unique, potent and selective inhibitors for Pim-1 and Pim-2 kinases: Chemistry, biological activities, and molecular modeling

  摘要：

  A series of isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones were synthesized as potent inhibitors against Pim-1 and Pim-2 kinases. The structure-activity-relationship studies started from a high-throughput screening hit and was guided by molecular modeling of inhibitors in the active site of Pim-1 kinase. Installing a hydroxyl group on the benzene ring of the core has the potential to form a key hydrogen bond interaction to the hinge region of the binding pocket and thus resulted in the most potent inhibitor, 19, with K-i values at 2.5 and 43.5 nM against Pim-1 and Pim-2, respectively. Compound 19 also exhibited an activity pro. le with a high degree of kinase selectivity. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.08.079
• 作为产物：
  描述：

  C₁₅H₁₅ClFNO₃S 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 7-Chloro-1-ethyl-6-fluoro-2-methanesulfinyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones as unique, potent and selective inhibitors for Pim-1 and Pim-2 kinases: Chemistry, biological activities, and molecular modeling

  摘要：

  A series of isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones were synthesized as potent inhibitors against Pim-1 and Pim-2 kinases. The structure-activity-relationship studies started from a high-throughput screening hit and was guided by molecular modeling of inhibitors in the active site of Pim-1 kinase. Installing a hydroxyl group on the benzene ring of the core has the potential to form a key hydrogen bond interaction to the hinge region of the binding pocket and thus resulted in the most potent inhibitor, 19, with K-i values at 2.5 and 43.5 nM against Pim-1 and Pim-2, respectively. Compound 19 also exhibited an activity pro. le with a high degree of kinase selectivity. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.08.079

文献信息

• Isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones as unique, potent and selective inhibitors for Pim-1 and Pim-2 kinases: Chemistry, biological activities, and molecular modeling
  作者：Yunsong Tong、Kent D. Stewart、Sheela Thomas、Magdalena Przytulinska、Eric F. Johnson、Vered Klinghofer、Joel Leverson、Owen McCall、Niru B. Soni、Yan Luo、Nan-horng Lin、Thomas J. Sowin、Vincent L. Giranda、Thomas D. Penning

  DOI：10.1016/j.bmcl.2008.08.079

  日期：2008.10

  A series of isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones were synthesized as potent inhibitors against Pim-1 and Pim-2 kinases. The structure-activity-relationship studies started from a high-throughput screening hit and was guided by molecular modeling of inhibitors in the active site of Pim-1 kinase. Installing a hydroxyl group on the benzene ring of the core has the potential to form a key hydrogen bond interaction to the hinge region of the binding pocket and thus resulted in the most potent inhibitor, 19, with K-i values at 2.5 and 43.5 nM against Pim-1 and Pim-2, respectively. Compound 19 also exhibited an activity pro. le with a high degree of kinase selectivity. (C) 2008 Elsevier Ltd. All rights reserved.