4-hydroxy-6-methyl-3-[7-(4-methylsulfanyl-phenyl)-2,3,6,7-tetrahydro-[1,4]thiazepin-5-yl]-pyran-2-one

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-hydroxy-6-methyl-3-[7-(4-methylsulfanyl-phenyl)-2,3,6,7-tetrahydro-[1,4]thiazepin-5-yl]-pyran-2-one
• 英文别名: 4-hydroxy-6-methyl-3-{7-[4-(methylsulfanyl)phenyl]-2,3,6,7-tetrahydro-1,4-thiazepin-5-yl}-2H-pyran-2-one；4-hydroxy-6-methyl-3-[7-(4-methylsulfanylphenyl)-2,3,6,7-tetrahydro-1,4-thiazepin-5-yl]pyran-2-one
• 化学式: C₁₈H₁₉NO₃S₂
• 分子量: 361.486
• InChiKey: SHXQFODSQRBJCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

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 4-hydroxy-6-methyl-3-[7-(4-methylsulfanyl-phenyl)-2,3,6,7-tetrahydro-[1,4]thiazepin-5-yl]-pyran-2-one
  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

• Substituted 1, 4-thiazepine and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Cytovia, Inc.

  公开号：US20020010169A1

  公开（公告）日：2002-01-24

  The present invention is directed to substituted 1,4-thiazepine and analogs thereof, represented by the general Formula I: 1 wherein the dashed lines, A 1 , A 2 , A 3 , X 1 and R 1 are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of capases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及被一般式I表示的取代的1,4-噻吩和其类似物，其中虚线、A1、A2、A3、X1和R1在此处被定义。本发明还涉及发现具有式I的化合物是卡泊酶激活剂和凋亡诱导剂。因此，本发明的卡泊酶激活剂和凋亡诱导剂可用于诱导在各种临床病况中发生细胞死亡，其中异常细胞的不受控制的生长和扩散。
• SUBSTITUTED 1,4-THIAZEPINE AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cytovia, Inc.

  公开号：EP1324993A2

  公开（公告）日：2003-07-09
• US6861419B2
  申请人：——

  公开号：US6861419B2

  公开（公告）日：2005-03-01
• [EN] SUBSTITUTED 1,4-THIAZEPINE AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF<br/>[FR] THIAZEPINE-1,4 SUBSTITUEE ET ANALOGUES DE CELLE-CI ACTIVATEURS DE CASPASES ET INDUCTEURS D'APOPTOSE, ET UTILISATION
  申请人：CYTOVIA INC

  公开号：WO2001079187A2

  公开（公告）日：2001-10-25

  The present invention is directed to substituted 1,4-thiazepine and analogs thereof, represented by the general Formula (I): wherein the dashed lines, A?1, A2, A3, X1 and R1¿ are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of capases and inducers of apoptosis. Therefore, the activators of caspases and inducers of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
• 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.