7-Methoxy-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine | 1479052-33-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 7-Methoxy-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine
• 英文别名: 7-methoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine
• CAS: 1479052-33-9
• 化学式: C₁₀H₁₃NOS
• 分子量: 195.285
• InChiKey: SZEPSWLFZWWADK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  46.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 7-Methoxy-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine 在 盐酸 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以91%的产率得到7-methoxy-5-methyl-2,3,4,5-tetrahydro-1,5-benzothiazepine
  参考文献：
  名称：

  Novel Carvedilol Analogues That Suppress Store-Overload-Induced Ca²⁺ Release

  摘要：

  Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part because of its ability to inhibit store-overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization, and bioassay of ca. 100 compounds based on the carvedilol motif to identify features that correlate with and optimize SOICR inhibition. A single-cell bioassay was employed on the basis of the RyR2-R4496C mutant HEK-293 cell line in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the beta-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits.

  DOI：

  10.1021/jm401090a
• 作为产物：
  描述：

  3-[(4-甲氧基苯基)硫基]丙酸 在 lithium aluminium tetrahydride 、 叠氮基三甲基硅烷 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 48.0h， 生成 7-Methoxy-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine
  参考文献：
  名称：

  Novel Carvedilol Analogues That Suppress Store-Overload-Induced Ca²⁺ Release

  摘要：

  Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part because of its ability to inhibit store-overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization, and bioassay of ca. 100 compounds based on the carvedilol motif to identify features that correlate with and optimize SOICR inhibition. A single-cell bioassay was employed on the basis of the RyR2-R4496C mutant HEK-293 cell line in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the beta-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits.

  DOI：

  10.1021/jm401090a

文献信息

• Novel Carvedilol Analogues That Suppress Store-Overload-Induced Ca²⁺ Release
  作者：Chris D. Smith、Aixia Wang、Kannan Vembaiyan、Jingqun Zhang、Cuihong Xie、Qiang Zhou、Guogen Wu、S. R. Wayne Chen、Thomas G. Back

  DOI：10.1021/jm401090a

  日期：2013.11.14

  Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part because of its ability to inhibit store-overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization, and bioassay of ca. 100 compounds based on the carvedilol motif to identify features that correlate with and optimize SOICR inhibition. A single-cell bioassay was employed on the basis of the RyR2-R4496C mutant HEK-293 cell line in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the beta-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits.