(4R-cis)-1-[3-[4-[3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]propyl]-4-aza-1-azoniabicyclo[2.2.2]octane methanesulfonate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫平类
• 英文名称: (4R-cis)-1-[3-[4-[3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]propyl]-4-aza-1-azoniabicyclo[2.2.2]octane methanesulfonate
• 英文别名: (4R,5R)-5-[4-[3-(4-aza-1-azoniabicyclo[2.2.2]octan-1-yl)propoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2H-1lambda6-benzothiepin-4-ol;methanesulfonate；(4R,5R)-5-[4-[3-(4-aza-1-azoniabicyclo[2.2.2]octan-1-yl)propoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2H-1λ6-benzothiepin-4-ol;methanesulfonate
• 化学式: CH₃O₃S*C₃₅H₅₄N₃O₄S
• 分子量: 707.996
• InChiKey: YEWXDNLMEDESNV-YDXXJHAFSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  48
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  144
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  Methanesulfonic acid 3-[4-((4R,5R)-3,3-dibutyl-7-dimethylamino-4-hydroxy-1,1-dioxo-2,3,4,5-tetrahydro-1H-1λ⁶-benzo[b]thiepin-5-yl)-phenoxy]-propyl ester 、 三乙烯二胺 以 乙腈 为溶剂， 生成 (4R-cis)-1-[3-[4-[3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]propyl]-4-aza-1-azoniabicyclo[2.2.2]octane methanesulfonate
  参考文献：
  名称：

  Discovery of Potent, Nonsystemic Apical Sodium-Codependent Bile Acid Transporter Inhibitors (Part 2)

  摘要：

  In the preceding paper several compounds were reported as potent apical. sodium-codependent bile acid transporter (ASBT) inhibitors. Since the primary site for active bile acid reabsorption is via ASBT, which is localized on the luminal surface of the distal ileum, we reasoned that a nonsystemic inhibitor would be desirable to minimize or eliminate potential systemic side effects of an absorbed drug. To ensure bioequivalency and product stability, it was also essential that we identify a nonhygroscopic inhibitor in its most stable crystalline form. A series of benzothiepines were prepared to refine the structure-activity relationship of the substituted phenyl ring at the 5-position of benzothiepine ring and to identify potent, crystalline, nonhygroscopic, and efficacious ASBT inhibitors with low systemic exposure.

  DOI：

  10.1021/jm0402162