2,2'-oxybis(N-(2-(2-(2-(2-((3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)sulfonamido)ethoxy)ethoxy)ethoxy)ethyl)acetamide) | 1234365-72-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 2,2'-oxybis(N-(2-(2-(2-(2-((3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)sulfonamido)ethoxy)ethoxy)ethoxy)ethyl)acetamide)
• 英文别名: 2,2'-oxybis(N-(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-l,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)acetamide)；2,2'-oxybis(N-(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)acetamide)；N-[2-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]-2-[2-[2-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetamide
• CAS: 1234365-72-0
• 化学式: C₅₂H₆₈Cl₄N₆O₁₃S₂
• 分子量: 1191.09
• InChiKey: OPWVGEUBXJEABG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  77
• 可旋转键数：
  34
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  238
• 氢给体数：
  4
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  2,3-二溴苯乙酮 在 sodium tetrahydroborate 、 硫酸 、 氯 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三甲基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 2,2'-oxybis(N-(2-(2-(2-(2-((3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)sulfonamido)ethoxy)ethoxy)ethoxy)ethyl)acetamide)
  参考文献：
  名称：

  Tenapanor 的发现：肠 Na+/H+ 交换异构体 3 的一流微系统抑制剂

  摘要：

  我们在此介绍了肠道限制性 Na + /H +交换异构体 3 (NHE3)抑制剂的设计、合成和优化。NHE3 主要在肾脏和胃肠道中表达，在那里它充当主要的吸收性钠转运蛋白。我们需要最低限度的全身性药物，可以阻止胃肠道中钠的吸收，但避免暴露在肾脏中。从相对低效的高生物利用度的命中化合物 ( 1 ) 开始，设计了有效且吸收最少的 NHE3 抑制剂，最终发现了替那帕诺 ( 28 )。Tenapanor 已被美国食品和药物管理局 (FDA) 批准用于治疗成人便秘型肠易激综合征。

  DOI：

  10.1021/acsmedchemlett.2c00037

文献信息

• [EN] GLYCYRRHETINIC ACID DERIVATIVES FOR TREATING HYPERKALEMIA<br/>[FR] DÉRIVÉS D'ACIDE GLYCYRRHÉTINIQUE DE TRAITEMENT DE L'HYPERKALIÉMIE
  申请人：ARDELYX INC

  公开号：WO2019060051A1

  公开（公告）日：2019-03-28

  The present invention provides a compound of formula (I) or a salt thereof: (I) wherein X, L, V, R1, R2, R3 and R4, are as defined herein. These compounds are inhibitors of 11-hydroxysteroid dehydrogenase type 2 (11-HSD-2) and are used to treat hyperkalemia.

  本发明提供了化合物(I)或其盐：(I)其中X、L、V、R1、R2、R3和R4如本文所定义。这些化合物是11-羟基类固醇脱氢酶2型（11-HSD-2）的抑制剂，用于治疗高钾血症。
• COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
  申请人：Charmot Dominique

  公开号：US20120263670A1

  公开（公告）日：2012-10-18

  The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

  本公开涉及化合物和方法，用于治疗与液体潴留或盐过载相关的疾病，如心力衰竭（特别是充血性心力衰竭）、慢性肾脏病、终末期肾脏病、肝病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂引起的液体潴留。本公开还涉及化合物和方法，用于治疗高血压。本公开还涉及化合物和方法，用于治疗胃肠道疾病，包括治疗或减轻与胃肠道疾病相关的疼痛。
• Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
  申请人：Ardelyx, Inc.

  公开号：US08969377B2

  公开（公告）日：2015-03-03

  The present disclosure is directed to compounds of the structure (X): wherein: n is 2 or 3; NHE has the structure wherein: R1 is H or —SO2—NR7R8—; R2 is selected from H, —NR7(CO)R8, —SO2—NR7R8— and —NR7R8; R3 is hydrogen; R7 is hydrogen; R8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO2—; and Y is selected from the group consisting of a bond, optionally substituted C1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH2)1-6O(CH2)1-6—, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及化合物的结构（X）：其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选择自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为与L连接的键；L为聚乙二醇连接体；以及Core具有以下结构：其中：X选择自一键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选择自一键，可选取取代的C1-6烷基，可选取取代的苯环，吡啶基，聚乙二醇连接体和—（CH2）1-6O（CH2）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏病和终末期肾脏病的方法。
• COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDER
  申请人：Ardelyx, Inc.

  公开号：US20150190389A1

  公开（公告）日：2015-07-09

  The present disclosure is directed to compounds of the structure (X): CoreL-NHE) n (X) wherein: n is 2 or 3; NHE has the structure wherein: R 1 is H or —SO 2 —NR 7 R 8 —; R 2 is selected from H, —NR 7 (CO)R 8 , —SO 2 —NR 7 R 8 — and —NR 7 R 8 ; R 3 is hydrogen; R 7 is hydrogen; R 8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO 2 —; and Y is selected from the group consisting of a bond, optionally substituted C 1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH 2 ) 1-6 O(CH 2 ) 1-6 —, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及结构为（X）：CoreL-NHE)n（X）的化合物，其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为连接到L的键；L为多聚乙二醇连接剂；Core具有以下结构：其中：X选自由键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选自键，可选择性地取代的C1-6烷基，可选择性地取代的苯，吡啶基，聚乙二醇连接剂和—（CH2）1-6O（CH2）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏病和终末期肾脏疾病的方法。
• Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorder
  申请人：Ardelyx, Inc.

  公开号：US09408840B2

  公开（公告）日：2016-08-09

  The present disclosure is directed to compounds of the structure (X): CoreL-NHE)n  (X) wherein: n is 2 or 3; NHE has the structure wherein: R1 is H or —SO2—NR7R8—; R2 is selected from H, —NR7(CO)R8, —SO2—NR7R8— and —NR7R8; R3 is hydrogen; R7 is hydrogen; R8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO2—; and Y is selected from the group consisting of a bond, optionally substituted C1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH2)1-6O(CH2)1-6—, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及结构式（X）：CoreL-NHE)n  (X)的化合物，其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为连接到L的键；L为多聚乙二醇连接体；Core具有以下结构：其中：X选自由键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选自自由键，可选取代的C1-6烷基，可选取代的苯，吡啶基，多聚乙二醇连接体和—（CH2）1-6O（CH2）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏疾病和终末期肾脏疾病的方法。