(S)-N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide

• 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: (S)-N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide
• 英文别名: US10543207, Example 202；N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]benzenesulfonamide
• 化学式: C₂₂H₂₉Cl₂N₃O₄S
• 分子量: 502.462
• InChiKey: IASCRFCWPXPWTQ-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide 在 盐酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 17-[[[3-[(4S)-6,8-dichloro-1,2,3,4-tetrahydro-2-methyl-4-isoquinolinyl]phenyl]sulphonyl]amino]-N-[2-[2-[2-[[[3-[(4S)-6,8-dichloro-1,2,3,4-tetrahydro-2-methyl-4-isoquinolinyl]phenyl]sulphonyl]amino]ethoxy]ethoxy]ethyl]-8-oxo-12,15-dioxa-2,7,9-triazaheptadecaneamide bishydrochloride salt
  参考文献：
  名称：

  [EN] SOLID FORMS OF TENAPANOR AND METHOD OF PREPARATION OF TENAPANOR
  [FR] FORMES SOLIDES DE TÉNAPANOR ET PROCÉDÉ DE PRÉPARATION DE TÉNAPANOR

  摘要：

  该发明涉及特纳帕诺的固体形式，特别是特纳帕诺游离碱的结晶形式I和固体特纳帕诺盐，以及其制备方法。结晶形式I是已知的特纳帕诺的第一种结晶形式。特纳帕诺的新型固体形式可用于特纳帕诺的纯化和/或在制药组合物中使用。此外，该发明提供了一种经济有效且可扩展的结晶特纳帕诺的制备方法。

  公开号：

  WO2019091503A1
• 作为产物：
  描述：

  (S)-tert-butyl (2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (S)-N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide
  参考文献：
  名称：

  苯磺酰胺类化合物及其制备方法和应用

  摘要：

  本发明公开了苯磺酰胺类化合物及其制备方法和应用，具体地，本发明公开了式(Ⅰ)所示化合物及其药效上可接受的盐，及其用于慢性肾病的治疗。

  公开号：

  CN114805202A

文献信息

• [EN] COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS<br/>[FR] COMPOSÉS ET PROCÉDÉS DESTINÉS À INHIBER UN ANTIPORT MÉDIÉ PAR NHE DANS LE TRAITEMENT DES TROUBLES ASSOCIÉS À UNE RÉTENTION DE FLUIDE OU À UNE SURCHARGE DE SEL ET DES TROUBLES DU TRACTUS GASTRO-INTESTINAL
  申请人：ARDELYX INC

  公开号：WO2014029984A1

  公开（公告）日：2014-02-27

  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治疗与液体潴留或盐过多有关的疾病的方法，例如心力衰竭（特别是充血性心力衰竭）、慢性肾病、晚期肾病、肝病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂诱导的液体潴留。本公开还涉及化合物和治疗高血压的方法。本公开还涉及化合物和治疗胃肠道疾病的方法，包括治疗或减轻与胃肠道疾病相关的疼痛。
• [EN] SOLID FORMS OF TENAPANOR AND METHOD OF PREPARATION OF TENAPANOR<br/>[FR] FORMES SOLIDES DE TÉNAPANOR ET PROCÉDÉ DE PRÉPARATION DE TÉNAPANOR
  申请人：ZENTIVA KS

  公开号：WO2019091503A1

  公开（公告）日：2019-05-16

  The invention relates to solid forms of tenapanor, in particular to crystalline form I of tenapanor free base and to solid tenapanor salts, and to methods of preparation thereof. The crystalline form I is the first known crystalline form of tenapanor. The novel solid forms of tenapanor can be used for purification of tenapanor and/or in pharmaceutical compositions. Furthermore, the invention provides a method of preparation of crystalline tenapanor which is economically effective and capable of being scaled up.

  该发明涉及特纳帕诺的固体形式，特别是特纳帕诺游离碱的结晶形式I和固体特纳帕诺盐，以及其制备方法。结晶形式I是已知的特纳帕诺的第一种结晶形式。特纳帕诺的新型固体形式可用于特纳帕诺的纯化和/或在制药组合物中使用。此外，该发明提供了一种经济有效且可扩展的结晶特纳帕诺的制备方法。
• [EN] SODIUM-HYDROGEN EXCHANGER 3 INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE L'ÉCHANGEUR SODIUM-HYDROGÈNE 3
  申请人：LILLY CO ELI

  公开号：WO2020231770A1

  公开（公告）日：2020-11-19

  The present invention relates to sodium-hydrogen exchanger 3 (NHE3) inhibitor compounds of the Formula: to pharmaceutical compositions comprising the compound and to the use of the compound for the treatment of certain diseases associated with elevated sodium and/or phosphate levels.

  本发明涉及一种公式为的钠-氢交换3（NHE3）抑制剂化合物：制备该化合物的药物组合物以及将该化合物用于治疗与升高的钠和/或磷水平相关的某些疾病的用途。
• 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 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。