氯马昔巴特 | 228113-66-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫平类
• 中文名称: 氯马昔巴特
• 英文名称: (4R-cis)-1-[[4-[[4-[3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]methyl]phenyl]methyl]-4-aza-1-azoniabicyclo[2.2.2]octane chloride
• 英文别名: maralixibat；(4R,5R)-1-[[4-[[4-[3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxo-1-benzothiepin-5-yl]phenoxy]methyl]phenyl]methyl]-4-aza-1-azoniabicyclo[2.2.2]octane chloride；Maralixibat Chloride；(4R,5R)-5-[4-[[4-(4-aza-1-azoniabicyclo[2.2.2]octan-1-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2H-1λ6-benzothiepin-4-ol;chloride
• CAS: 228113-66-4
• 化学式: C₄₀H₅₆N₃O₄S*Cl
• 分子量: 710.421
• InChiKey: POMVPJBWDDJCMP-RUKDTIIFSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  49
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  78.5
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

毒理性

• 在妊娠和哺乳期间的影响

母乳喂养期间使用总结：目前没有关于在哺乳期间使用马瑞利昔巴特的信息。由于马瑞利昔巴特口服吸收不良且90%与血浆蛋白结合，乳汁中的量可能较低。如果母亲需要使用马瑞利昔巴特，这并不是停止哺乳的理由。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:No information is available on the use of maralixibat during breastfeeding. Because maralixibat is poorly absorbed orally and 90% bound to plasma proteins, the amount in milk is likely to be low. If maralixibat is required by the mother, it is not a reason to discontinue breastfeeding. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为产物：
  描述：

  (4R,5R)-3,3-dibutyl-5-[4-[[4-(chloromethyl)phenyl]methoxy]phenyl]-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2H-1lambda6-benzothiepin-4-ol 、 三乙烯二胺 以 乙腈 为溶剂， 反应 2.0h， 生成 氯马昔巴特
  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

• Novel benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
  申请人：G.D. Searle & Co.

  公开号：US20020013476A1

  公开（公告）日：2002-01-31

  Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals.

  提供了新型苯并噻吩类化合物及其衍生物和类似物；含有它们的药物组合物；以及在医学中使用这些化合物和组合物的方法，特别是在哺乳动物中预防和治疗高脂血症状，如与动脉粥样硬化或高胆固醇血症相关的情况。
• Novel benzothiepines having activity as inhibitors of lleal bile acid transport and taurocholate uptake
  申请人：G.D. Searle & Co.

  公开号：US20040014803A1

  公开（公告）日：2004-01-22

  Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals.

  提供了新型苯硫杂吲哚类化合物及其衍生物和类似物；含有它们的药物组合物；以及在医学中使用这些化合物和组合物的方法，特别是在哺乳动物中预防和治疗高脂血症状，如与动脉粥样硬化或高胆固醇血症相关的情况。
• Novel mono- and di-fluorinated beozothiepine copmunds as inhibitors of apical sodium co-dependent bile acid transport (ASBT) and taurocholate uptake
  申请人：G.D. SEARLE, LLC

  公开号：US20040176438A1

  公开（公告）日：2004-09-09

  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.

  本文披露了单氟和双氟苯并噻吩顶部钠依赖性胆汁酸转运体（ASBT）抑制剂的方法，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状况的方法，以及含有这些化合物的制药组合物。
• Preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
  申请人：G.D. Searle & Co.

  公开号：EP1466911A2

  公开（公告）日：2004-10-13

  Methods are provided for preparing benzothiepines, derivatives, and analogs thereof, which have activity as inhibitors of ileal bile acid transport and taurocholate uptake.

  本研究提供了制备苯并噻吩类、其衍生物和类似物的方法，它们具有作为回肠胆汁酸转运和牛磺胆酸盐摄取抑制剂的活性。
• Sickle cell disease treatment utilizing omega-3 fatty acids
  申请人：Micelle BioPharma, Inc.

  公开号：US10894027B2

  公开（公告）日：2021-01-19

  Described herein are compositions including at least one omega-3 fatty acid (either in the triglyceride, ester or free fatty acid ester form) and at least one surface active agent; wherein the compositions form micelles when in contact with an aqueous medium. Also provided are methods of administering to a subject a composition including at least one omega-3 fatty acid (either in the triglyceride, ester or free fatty acid ester form) and at least one surface active agent, wherein the compositions form micelles when in contact with an aqueous medium, and the bioavailability of the omega-3 fatty acid is substantially independent of a food effect. The compositions are useful for treating certain disease states which may include (1) malabsorption syndromes, (2) primary sclerosing cholangitis (PSC), (3) non-alcoholic fatty liver disease (NAFLD), (4) sickle cell disease (SCD), (5) age-related macular degeneration (AMD), and (6) neurodegenerative disease, including, Parkinson's Disease (PD), Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease), Epilepsy, Bi-polar Syndrome, traumatic brain injury, peripheral neuropathy, and Multiple Sclerosis (MS). Described are also various dosage forms for administering the compositions and use of the compositions in functional foods. Provided herein are also kits with instructions for their administration.

  本文描述了包括至少一种欧米伽-3 脂肪酸（甘油三酯、酯或游离脂肪酸酯形式）和至少一种表面活性剂的组合物；其中组合物在与水介质接触时形成胶束。还提供了向受试者施用包括至少一种欧米伽-3 脂肪酸（甘油三酯、酯或游离脂肪酸酯形式）和至少一种表面活性剂的组合物的方法，其中组合物在与水介质接触时形成胶束，且欧米伽-3 脂肪酸的生物利用度基本上不受食物影响。这些组合物可用于治疗某些疾病，包括：（1）吸收不良综合征；（2）原发性硬化性胆管炎（PSC）；（3）非酒精性脂肪肝（NAFLD）；（4）镰状细胞病（SCD）；（5）老年性黄斑变性（AMD）；以及（6）神经退行性疾病、和 (6) 神经退行性疾病，包括帕金森病 (PD)、阿尔茨海默病 (AD)、肌萎缩侧索硬化症 (ALS 或卢伽雷氏病)、癫痫、双极综合征、脑外伤、周围神经病变和多发性硬化症 (MS)。本文还描述了施用组合物的各种剂型以及组合物在功能性食品中的用途。本文还提供了附有使用说明的试剂盒。