(4R,5R)-3,3-Dibutyl-7-dimethylamino-5-(3-hydroxy-phenyl)-1,1-dioxo-2,3,4,5-tetrahydro-1H-1λ⁶-benzo[b]thiepin-4-ol

• 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,5R)-3,3-Dibutyl-7-dimethylamino-5-(3-hydroxy-phenyl)-1,1-dioxo-2,3,4,5-tetrahydro-1H-1λ⁶-benzo[b]thiepin-4-ol
• 英文别名: (4R,5R)-3,3-dibutyl-7-(dimethylamino)-5-(3-hydroxyphenyl)-1,1-dioxo-4,5-dihydro-2H-1lambda6-benzothiepin-4-ol；(4R,5R)-3,3-dibutyl-7-(dimethylamino)-5-(3-hydroxyphenyl)-1,1-dioxo-4,5-dihydro-2H-1λ6-benzothiepin-4-ol
• 化学式: C₂₆H₃₇NO₄S
• 分子量: 459.65
• InChiKey: MNUCZVZYUTVEJV-JWQCQUIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,5R)-3,3-Dibutyl-7-dimethylamino-5-(3-hydroxy-phenyl)-1,1-dioxo-2,3,4,5-tetrahydro-1H-1λ⁶-benzo[b]thiepin-4-ol 在 吡啶 、 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 3-((4R,5R)-3,3-Dibutyl-7-dimethylamino-4-hydroxy-1,1-dioxo-2,3,4,5-tetrahydro-1H-1λ⁶-benzo[b]thiepin-5-yl)-benzoic acid methyl ester
  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
• 作为产物：
  描述：

  (4R,5R)-3,3-Dibutyl-7-dimethylamino-5-(3-methoxy-phenyl)-1,1-dioxo-2,3,4,5-tetrahydro-1H-1λ⁶-benzo[b]thiepin-4-ol 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 (4R,5R)-3,3-Dibutyl-7-dimethylamino-5-(3-hydroxy-phenyl)-1,1-dioxo-2,3,4,5-tetrahydro-1H-1λ⁶-benzo[b]thiepin-4-ol
  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

文献信息

• Discovery of Potent, Nonsystemic Apical Sodium-Codependent Bile Acid Transporter Inhibitors (Part 2)
  作者：Horng-Chih Huang、Samuel J. Tremont、Len F. Lee、Bradley T. Keller、Andrew J. Carpenter、Ching-Cheng Wang、Shyamal C. Banerjee、Scott R. Both、Theresa Fletcher、Danny J. Garland、Wei Huang、Claude Jones、Kevin J. Koeller、Steve A. Kolodziej、James Li、Robert E. Manning、Matthew W. Mahoney、Raymond E. Miller、Deborah A. Mischke、Nigam P. Rath、Emily J. Reinhard、Michael B. Tollefson、William F. Vernier、Grace M. Wagner、Steve R. Rapp、Judy Beaudry、Kevin Glenn、Karen Regina、Joe R. Schuh、Mark E. Smith、Jay S. Trivedi、David B. Reitz

  DOI：10.1021/jm0402162

  日期：2005.9.1

  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.