5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(4-isopropylphenyl)-2,3,6,7-tetrahydro-1,4-thiazepine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(4-isopropylphenyl)-2,3,6,7-tetrahydro-1,4-thiazepine
• 英文别名: 2-hydroxy-6-methyl-3-{7-[4-(propan-2-yl)phenyl]-2,3,6,7-tetrahydro-1,4-thiazepin-5-yl}-4H-pyran-4-one；4-hydroxy-6-methyl-3-[7-(4-propan-2-ylphenyl)-2,3,6,7-tetrahydro-1,4-thiazepin-5-yl]pyran-2-one
• 化学式: C₂₀H₂₃NO₃S
• 分子量: 357.474
• InChiKey: OTNIHYCQZPHTNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  去氢乙酸 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(4-isopropylphenyl)-2,3,6,7-tetrahydro-1,4-thiazepine
  参考文献：
  名称：

  Discovery of 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-(E)-2,3,6,7-tetrahydro-1,4-thiazepines as a new series of apoptosis inducers using a cell- and caspase-based HTS assay

  摘要：

  We report the discovery of 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(4-methylphenyl)-(E)-2,3,6,7-tetrahydro-1,4-thiazepine (2a) as an inducer of apoptosis using our proprietary cell- and caspase-based HTS assay. Through structure activity relationship (SAR) studies, 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(2-methoxy-4-(methylthio)phenyl)-(E)-2,3,6,7-tetrahydro-1,4-thiazepine (5d) was identified as a potent apoptosis inducer with an EC50 value of 0.08 mu M in T47D cells, which was > 15-fold more potent than screening hit 2a. Compound 5d also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.05 mu M in T47D cells and to function as an inhibitor of tubulin polymerization. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.098

文献信息

• Discovery of 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-(E)-2,3,6,7-tetrahydro-1,4-thiazepines as a new series of apoptosis inducers using a cell- and caspase-based HTS assay
  作者：John Drewe、Shailaja Kasibhatla、Ben Tseng、Emma Shelton、David Sperandio、Robert M. Yee、Joane Litvak、Martin Sendzik、Jeffrey R. Spencer、Sui Xiong Cai

  DOI：10.1016/j.bmcl.2007.05.098

  日期：2007.9

  We report the discovery of 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(4-methylphenyl)-(E)-2,3,6,7-tetrahydro-1,4-thiazepine (2a) as an inducer of apoptosis using our proprietary cell- and caspase-based HTS assay. Through structure activity relationship (SAR) studies, 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(2-methoxy-4-(methylthio)phenyl)-(E)-2,3,6,7-tetrahydro-1,4-thiazepine (5d) was identified as a potent apoptosis inducer with an EC50 value of 0.08 mu M in T47D cells, which was > 15-fold more potent than screening hit 2a. Compound 5d also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.05 mu M in T47D cells and to function as an inhibitor of tubulin polymerization. (c) 2007 Elsevier Ltd. All rights reserved.