(+)-(4R,5R)-3,3-dibutyl-7-(dimethylamino)-5-(4'-hydroxyphenyl)-2,3,4,5-tetrahydro-1-benzothiepin-4-ol 1,1-dioxide | 228113-65-3

• 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-(4'-hydroxyphenyl)-2,3,4,5-tetrahydro-1-benzothiepin-4-ol 1,1-dioxide
• 英文别名: (4R,5R)-3,3-dibutyl-7-(dimethylamino)-1,1-dioxido-4-hydroxy-5-(4-hydroxyphenyl)-2,3,4,5-tetrahydrobenzothiepine；(4R,5R)-3,3-dibutyl-7-(dimethylamino)-5-(4-hydroxyphenyl)-1,1-dioxo-4,5-dihydro-2H-1λ6-benzothiepin-4-ol
• CAS: 228113-65-3
• 化学式: C₂₆H₃₇NO₄S
• 分子量: 459.65
• InChiKey: ZISCLBWDEGJRBM-JWQCQUIFSA-N

物化性质

• 沸点：
  639.7±55.0 °C(Predicted)
• 密度：
  1.155±0.06 g/cm3(Predicted)

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-(4'-hydroxyphenyl)-2,3,4,5-tetrahydro-1-benzothiepin-4-ol 1,1-dioxide 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 74.0h， 生成 (+)-5-{4-[(4R,5R)-3,3-dibutyl-7-(dimethylamino)-4-hydroxy-1,1-dioxido-2,3,4,5-tetrahydro-1-benzothiepin-5-yl]phenoxy}-N,N,N-triethylpentan-1-aminium bromide
  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-(4-methoxyphenyl)-1,1-dioxo-4,5-dihydro-2H-1λ6-benzothiepin-4-ol 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以82%的产率得到(+)-(4R,5R)-3,3-dibutyl-7-(dimethylamino)-5-(4'-hydroxyphenyl)-2,3,4,5-tetrahydro-1-benzothiepin-4-ol 1,1-dioxide
  参考文献：
  名称：

  Method of preparing enantiomerically-enriched tetrahydrobenzothiepine oxides

  摘要：

  一种制备对映富集的四氢苯并噻吩氧化物的过程，包括环化对映富集的芳基-3-丙醛亚磺酸盐，其中芳基-3-丙醛亚磺酸盐的硫原子是手性中心。

  公开号：

  US06369220B1

文献信息

• Method for the preparation of crystalline tetrahydrobenzothiepines
  申请人：G.D. SEARLE, LLC

  公开号：US20030199515A1

  公开（公告）日：2003-10-23

  Among its several embodiments, the present invention provides an improved process for the preparation of tetrahydrobenzothiepine-1,1-dioxide compounds; the provision of a process for preparing a diastereomeric mixture of tetrahydrobenzothiepine-1,1-dioxide compounds from a single diastereomer of such compounds; the provision of a process for the preparation of 3-bromo-2-substituted propionaldehyde compounds; the provision of a process for the preparation of 3-thio-2-substituted propionaldehyde compounds; and the provision of a process for the preparation of single crystals of ASBT inhibitors having high purity and low levels of solvent impurities.

  在其几个实施例中，本发明提供了一种改进的制备四氢苯并噻吩-1,1-二氧化物化合物的方法；提供了一种从单个该类化合物的对映异构体制备四氢苯并噻吩-1,1-二氧化物混合物的方法；提供了一种制备3-溴-2-取代丙醛化合物的方法；提供了一种制备3-硫-2-取代丙醛化合物的方法；以及提供了一种制备高纯度且溶剂杂质含量低的ASBT抑制剂单晶的方法。
• Method for the preparation of tetrahydrobenzothiepines
  申请人：——

  公开号：US20020032329A1

  公开（公告）日：2002-03-14

  Among its several embodiments, the present invention provides an improved process for the preparation of tetrahydrobenzothiepine-1,1-dioxide compounds; the provision of a process for preparing a diastereomeric mixture of tetrahydrobenzothiepine-1,1-dioxide compounds from a single diastereomer of such compounds; the provision of a process for the preparation of 3-bromo-2-substituted propionaldehyde compounds; and the provision of a process for the preparation of 3-thio-2-substituted propionaldehyde compounds.

  在其几种具体实施方式中，本发明提供了一种改进的制备四氢苯并噻吩-1,1-二氧化物化合物的过程；提供了一种从单个对映异构体化合物的对映异构体混合物中制备四氢苯并噻吩-1,1-二氧化物化合物的过程；提供了一种制备3-溴-2-取代丙醛化合物的过程；以及提供了一种制备3-硫代-2-取代丙醛化合物的过程。
• Method of preparing enantiomerically-enriched tetrahydrobenzothiepine oxides
  申请人：——

  公开号：US06369220B1

  公开（公告）日：2002-04-09

  A process for preparing enantiomerically enriched tetrahydrobenzothipeine oxides comprises cyclizing an enantiomerically enriched aryl-3-propanalsulfoxide wherein the sulfur atom of the aryl-3-propanalsulfoxide is a chiral center.

  一种制备对映富集的四氢苯并噻吩氧化物的过程，包括环化对映富集的芳基-3-丙醛亚磺酸盐，其中芳基-3-丙醛亚磺酸盐的硫原子是手性中心。
• Novel mono- and di-fluorinated benzothiepine compouds as inhibitors of apical sodium co-dependent bile acid transport (ASBT) and taurocholate uptake
  申请人：G.D. SEARLE, LLC

  公开号：US20040067872A1

  公开（公告）日：2004-04-08

  Mono-fluorinated and di-fluorinated benzothiepine apical sodium co-dependent bile acid transport (ASBT) inhibitors are disclosed together with methods of making the same, methods of using the same to treat hyperlipidemic conditions as well as pharmaceutical compositions containing the same compounds.

  本发明公开了单氟和二氟苯并噻吩顶部钠依赖性胆酸转运体（ASBT）抑制剂，以及制备这些抑制剂的方法，使用这些抑制剂治疗高脂血症的方法，以及含有这些化合物的药物组合物。
• Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders
  申请人：G.D. SEARLE LLC

  公开号：US20040110761A1

  公开（公告）日：2004-06-10

  Novel methods and combinations for the treatment and/or prophylaxis of a hyperlipidernic condition or disorder in a subject, wherein the methods comprise the administration of one or more HMG Co-A reductase inhibitors and one or more ASBT inhibitors selected from the specific group of compounds described herein, and the combinations comprise one or more HMG Co-A reductase inhibitors and one or more of said apical sodium co-dependent bile acid transport inhibitors.

  本发明涉及用于治疗和/或预防受体内高脂血症状况或疾病的新方法和组合，其中所述方法包括向受体内给予一种或多种HMG Co-A还原酶抑制剂和一种或多种从本文所述的特定化合物组中选择的ASBT抑制剂的给药，所述组合包括一种或多种HMG Co-A还原酶抑制剂和一种或多种所述顶端钠共依赖性胆酸转运抑制剂。