1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-(carboxymethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine | 501692-12-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-(carboxymethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine
• 英文别名: 1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-(carboxymethyl)carbamoyl]benzyl} carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine；2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]acetic acid；2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1λ6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]acetic acid
• CAS: 501692-12-2
• 化学式: C₃₅H₄₄N₄O₇S₂
• 分子量: 696.889
• InChiKey: SKKDVDAOVWNTOW-MGBGTMOVSA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  48
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  188
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (R)-2-(2-(((苄氧基)羰基)氨基)-2-苯基乙酰氨基)乙酸乙酯 在 N-甲基吗啉 、 palladium 10% on activated carbon 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 18.0~25.0 ℃ 、101.33 kPa 条件下， 反应 6.5h， 生成 1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-(carboxymethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine
  参考文献：
  名称：

  BENZOTHIAZEPINE AND BENZOTHIADIAZEPINE DERIVATIVES WITH ILEAL BILE ACID TRANSPORT (IBAT) INHIBITORY ACTIVITY FOR THE TREATMENT HYPERLIPIDAEMIA

  摘要：

  公开号：

  EP1427423B9

文献信息

• Bile Acid Recycling Inhibitors for Treatment of Hypercholemia and Cholestatic Liver Disease
  申请人：Lumena Pharmaceuticals, Inc.

  公开号：US20130108573A1

  公开（公告）日：2013-05-02

  Provided herein are methods of treating or ameliorating hypercholemia or a cholestatic liver disease by administering to an individual in need thereof a therapeutically effective amount of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising administering to an individual in need thereof a therapeutically effective amount of ASBTI or a pharmaceutically acceptable salt thereof.

  本文提供了一种治疗或改善高胆固醇血症或胆汁淤积性肝病的方法，即通过向需要的个体施用治疗有效量的顶端钠依赖性胆酸转运蛋白抑制剂（ASBTI）或其药用可接受盐。还提供了一种治疗或改善肝病、降低血清胆酸或肝内胆酸水平、治疗或改善瘙痒、降低肝酶或减少胆红素的方法，即通过向需要的个体施用治疗有效量的ASBTI或其药用可接受盐。
• Benzothiazepine and benzothiazepine derivatives with ileal bile acid transport (ibat) inhibitory activity for the treatment hyperlipidaemia
  申请人：Starke Ingemar

  公开号：US20050038009A1

  公开（公告）日：2005-02-17

  The present invention relates to compounds of formula (I) wherein R v , R 1 , R 2 , R x , R y , M, R z , v, R 3 , R 4 , R 5 and R 6 are as defined within; pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as ileal bile acid transport (IBAT) inhibitors for the treatment of hyperlipidaemia. Processes for their manufacture and pharmaceutical compositions containing them are also described.

  本发明涉及式(I)化合物，其中Rv、R1、R2、Rx、Ry、M、Rz、v、R3、R4、R5和R6的定义如下；药学上可接受的盐、溶剂、这些盐的溶剂和其前药，并且它们的用途是作为追随性胆汁酸转运（IBAT）抑制剂，用于治疗高脂血症。还描述了它们的制造过程和包含它们的制药组合物。
• Bile Acid Recycling Inhibitors for Treatment of Pediatric Cholestatic Liver Diseases
  申请人：Lumena Pharmaceuticals, Inc.

  公开号：US20130109671A1

  公开（公告）日：2013-05-02

  Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.

  本文提供了一种通过非系统性给予需要治疗或改善儿童胆汁淤积性肝病的个体治疗的方法，该方法包括给予含有顶端钠依赖性胆酸转运体抑制剂（ASBTI）或其药学上可接受的盐的儿科制剂的治疗有效量。此外，还提供了一种治疗或改善儿童肝病、降低血清胆酸或肝胆酸水平、治疗或改善瘙痒、降低肝酶或减少胆红素的方法，该方法包括给予含有ASBTI或其药学上可接受的盐的儿科制剂的治疗有效量。
• BILE ACID RECYCLING INHIBITORS FOR TREATMENT OF HYPERCHOLEMIA AND CHOLESTATIC LIVER DISEASE
  申请人：Lumena Pharmaceuticals, Inc.

  公开号：US20140323412A1

  公开（公告）日：2014-10-30

  Provided herein are methods of treating or ameliorating hypercholemia or a cholestatic liver disease by administering to an individual in need thereof a therapeutically effective amount of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising administering to an individual in need thereof a therapeutically effective amount of ASBTI or a pharmaceutically acceptable salt thereof.

  本文提供的是治疗或改善高胆固醇血症或胆汁淤积性肝病的方法，通过向需要治疗的个体施用治疗有效量的顶端钠依赖性胆酸转运体抑制剂（ASBTI）或其药学上可接受的盐。还提供了治疗或改善肝病、降低血清胆汁酸或肝胆汁酸水平、治疗或改善瘙痒症、降低肝酶或胆红素的方法，通过向需要治疗的个体施用治疗有效量的ASBTI或其药学上可接受的盐。
• BILE ACID RECYCLING INHIBITORS FOR TREATMENT OF PEDIATRIC CHOLESTATIC LIVER DISEASES
  申请人：Lumena Pharmaceuticals, Inc.

  公开号：US20140243281A1

  公开（公告）日：2014-08-28

  Provided herein are pediatric dosage forms for use in the treatment of a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of the pediatric dosage form comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are said pediatric dosage form for use in the treatment of a pediatric liver disease, for use in decreasing the levels of serum bile acids or hepatic bile acids, for use in the treatment of pruritis, for use in reducing liver enzymes or bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.

  本文提供了用于治疗儿童胆汁淤积性肝病的儿童剂型，通过非系统性给予需要治疗的个体含有顶端钠依赖性胆酸转运体抑制剂（ASBTI）或其药学上可接受的盐的治疗有效量的儿童剂型。还提供了该儿童剂型用于治疗儿童肝病，用于降低血清胆酸或肝胆酸水平，用于治疗瘙痒症，用于减少肝酶或胆红素的儿童制剂，通过非系统性给予需要治疗的个体含有ASBTI或其药学上可接受的盐的治疗有效量。