1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-{(S)-1-[N-((S)-2-hydroxy-1-carboxyethyl)carbamoyl]propyl}carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine | 501692-50-8

• 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-{(S)-1-[N-((S)-2-hydroxy-1-carboxyethyl)carbamoyl]propyl}carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine
• 英文别名: (2S)-2-[[(2S)-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]butanoyl]amino]-3-hydroxypropanoic acid；(2S)-2-[[(2S)-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]butanoyl]amino]-3-hydroxypropanoic acid
• CAS: 501692-50-8
• 化学式: C₄₀H₅₃N₅O₉S₂
• 分子量: 812.021
• InChiKey: BMFYEGAXUFVWIC-PTVSMQAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  56
• 可旋转键数：
  20
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  237
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-[N-((R)-α-carboxybenzyl)carbamoylmethoxy]-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine 在 N-甲基吗啉 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 116.5h， 生成 1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-{(S)-1-[N-((S)-2-hydroxy-1-carboxyethyl)carbamoyl]propyl}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。
• Therapeutic agents
  申请人：Alstermark Lindstedt Eva-Lotte

  公开号：US20050282822A1

  公开（公告）日：2005-12-22

  The present invention provides a compound of formula I processes for preparing such compounds, their the utility in treating clinical conditions including lipid disorders (dyslipidemias) whether or not associated with insulin resistance, methods for their therapeutic use and pharmaceutical compositions containing them.

  本发明提供了一种I式化合物，以及制备这种化合物的方法，它们在治疗临床病症中的应用，包括与胰岛素抵抗有关的脂质紊乱（脂质代谢异常），以及它们的治疗用途和含有它们的药物组合物。
• [EN] ORTHO-SUBSTITUTED BENZOIC ACID DERIVATIVES FOR THE TREATMENT OF INSULIN RESISTANCE<br/>[FR] DERIVES DE L'ACIDE BENZOIQUE ORTHO-SUBSTITUES DESTINES AU TRAITEMENT DE L'INSULINORESISTANCE
  申请人：ASTRAZENECA AB

  公开号：WO2004000790A1

  公开（公告）日：2003-12-31

  The present invention provides a compound of formula (I), wherein n is 0, 1 or 2 and R1 represents halo, a C1-4alkyl group which is optionally substituted by one or more fluoro, a C1-4alkoxy group which is optionally substituted by one or more fluoro and wherein when n is 2 the substituents R1 may be the same or different; R2 represents a C2-8alkyl group which is optionally interrupted by oxygen; Y is absent or represents methylene; and X is O or S; and pharmaceutically acceptable salts and prodrugs thereof, to processes for preparing such compounds, to their utility in treating clinical conditions associated with insulin resistance, to methods for their therapeutic use and to pharmaceutical compositions containing them.

  本发明提供了一种化合物，其化学式为(I)，其中n为0、1或2，R1代表卤素、一种或多种氟代取代的C1-4烷基基团、一种或多种氟代取代的C1-4烷氧基基团，当n为2时，取代基R1可以相同也可以不同；R2代表一个C2-8烷基基团，可由氧原子中断；Y为不存在或代表亚甲基；X为O或S；以及其药学上可接受的盐和前药，用于制备这种化合物的方法，它们在治疗与胰岛素抵抗相关的临床病况中的用途，以及用于治疗的方法和含有它们的药物组合物。
• [EN] THERAPEUTIC AGENTS<br/>[FR] AGENTS THERAPEUTIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2004056748A1

  公开（公告）日：2004-07-08

  The present invention provides the S enantiomer of a compound of formula (I) wherein R1 represents chloro, trifluoromethyl or trifluoromethoxy, R2 represents H or fluoro and R3 represents a C2-4alkyl group as well as pharmaceutically acceptable salts, solvates and prodrugs thereof, to processes for preparing such compounds, to their the utility in treating clinical conditions including lipid disorders (dyslipidemias) whether or not associated with insulin resistance, to methods for their therapeutic use and to pharmaceutical compositions containing them.

  本发明提供了公式(I)中R1代表氯、三氟甲基或三氟甲氧基，R2代表H或氟，R3代表C2-4烷基的化合物的S对映体，以及其药学上可接受的盐、溶剂化合物和前药，以及制备这些化合物的方法，它们在治疗临床病症包括脂质紊乱（失调脂质症）方面的用途，无论是否与胰岛素抵抗有关，以及它们的治疗用途和含有它们的制药组合物。
• Diphenylazetidinone derivatives for treating disorders of the lipid metabolism
  申请人：Starke Ingemar

  公开号：US20050239766A1

  公开（公告）日：2005-10-27

  Compounds of formula (I): (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described. Processes for their manufacture and pharmaceutical compositions containing them are also described.

  本文描述了公式(I)的化合物：(其中变量基团的定义如下)、药学上可接受的盐、该盐的溶剂合物、该盐的溶剂合物的前药及其用作治疗高血脂症的胆固醇吸收抑制剂的用途。还描述了它们的制造过程和含有它们的制药组合物。