4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonyl chloride | 543739-88-4

• 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: 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonyl chloride
• 英文别名: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonyl chloride；4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)benzenesulfonyl chloride
• CAS: 543739-88-4
• 化学式: C₁₆H₁₄Cl₃NO₂S
• 分子量: 390.718
• InChiKey: NIEVPMJEVHSEIJ-UHFFFAOYSA-N

物化性质

• 沸点：
  471.2±45.0 °C(Predicted)
• 密度：
  1.436±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonyl chloride 、 胍 在 盐酸 作用下， 以 四氢呋喃 、 乙醚 、 乙酸乙酯 为溶剂， 反应 29.0h， 生成 N-Diaminomethylene-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)benzenesulfonamide, dihydrochloride
  参考文献：
  名称：

  SUBSTITUTED 4-PHENYLTETRAHYDROISOQUINOLINES, PROCESS FOR THEIR PREPARATION, PHARMACEUTICAL COMPOSITIONS AND THERAPEUTIC USE

  摘要：

  本发明涉及取代的4-苯基四氢异喹啉化合物和包含它们的制药组合物，这些化合物是优秀的钠-氢交换酶（NHE）抑制剂，特别是亚型3（NHE-3）的钠-氢交换酶抑制剂。因此，这些化合物在治疗各种肾和呼吸系统疾病方面非常有用，例如急性或慢性肾衰竭，肺部并发症，胆功能障碍，呼吸系统疾病，如打鼾或睡眠呼吸暂停以及心血管/中枢神经系统疾病，例如中风。更具体地说，本发明涉及由公式I定义的取代的4-苯基四氢异喹啉，其中R1-R8在此定义。

  公开号：

  US20080194621A1
• 作为产物：
  描述：

  6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline 、 氯磺酸 、 sodium hydroxide 在 ice 、 乙酸乙酯 、 Sodium sulfate-III 作用下， 反应 3.0h， 生成 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonyl chloride
  参考文献：
  名称：

  Substituted 4-phenyltetrahydroisoquinolinium, process for their preparation, their use as a medicament, and medicament containing them

  摘要：

  本发明涉及公式I1中R1至R9所定义的化合物。在一个实施例中，这些化合物可用作降压剂，用于减少或预防缺血引起的损伤，作为治疗神经系统、中风和脑水肿、休克、呼吸驱动力受损、打鼾的药物，作为泻药，对抗外寄生虫的药剂，预防胆结石的形成，作为抗动脉粥样硬化药物，对抗糖尿病的晚期并发症、癌症、纤维性疾病、内皮功能障碍、器官肥大和增生。在一个实施例中，这些化合物可能是细胞钠质子抗转运蛋白的抑制剂，影响血清脂蛋白，因此可用于动脉粥样硬化病变的预防和回归。

  公开号：

  US20040044211A1

文献信息

• METHODS FOR THE IMPROVEMENT OF MEMORY AND NEUROLOGICAL FUNCTION COMPRISING THE ADMINISTRATION OF COMPOSITIONS THAT ACT AS INHIBITORS OF THE SODIUM PROTON (NA+ /H+ ) EXCHANGER, SUBTYPE 5 (NHE-5)
  申请人：KLEEMANN Heinz-Werner

  公开号：US20080234317A1

  公开（公告）日：2008-09-25

  The present invention comprises the use of pharmaceutical compositions that are effective in the inhibition of the Na + /H + exchanger, subtype 5 (NHE-5) as inhibitors of cellular NHE-5 enhance long term potentiation (LTP) and are therefore effective in the treatment of memory impairments, dementing disorders, and for improving memory. Particularly suitable for the treatment of neurodegenerative disorders, memory impairments and dementing disorders, and for improving memory, are the following NHE-5 inhibitors of the formula I Wherein the R1-R8 substituents are further defined herein:

  本发明涉及使用药物组合物作为Na+/H+交换器亚型5（NHE-5）的抑制剂，这些抑制剂可以增强长期增强（LTP）并因此有效治疗记忆障碍、痴呆疾病和改善记忆。特别适用于治疗神经退行性疾病、记忆障碍和痴呆疾病，以及改善记忆的是以下公式I的NHE-5抑制剂，其中R1-R8取代基在此进一步定义：
• 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。
• Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, pharmaceutical compositions and therapeutic use
  申请人：Lang Hans-Jochen

  公开号：US08455515B2

  公开（公告）日：2013-06-04

  The present invention relates to substituted 4-phenyltetrahydroisoquinoline compounds and pharmaceutical compositions comprising them which are excellent inhibitors of the sodium-hydrogen exchanger (NHE), in particular of the sodium-hydrogen exchanger of subtype 3 (NHE-3). As such these compounds are useful in the treatment of various disorders of the renal and respiratory systems such as acute or chronic renal failure, pulmonary complications, biliary function disorders, respiratory disorders such as snoring or sleep apneas and cardiovascular/central nervous system disorders such as stroke. More specifically, the present invention relates to substituted 4-phenyl-tetrahydroisoquinolines defined by the formula I in which R1-R8 are defined herein.

  本发明涉及替代的4-苯基四氢异喹啉化合物和包含它们的制药组合物，这些组合物是钠-氢交换器（NHE）的优秀抑制剂，特别是亚型3（NHE-3）的钠-氢交换器。因此，这些化合物在治疗各种肾脏和呼吸系统的疾病方面非常有用，如急性或慢性肾衰竭、肺部并发症、胆功能障碍、呼吸障碍如打鼾或睡眠呼吸暂停以及心血管/中枢神经系统疾病如中风。更具体地说，本发明涉及由式I定义的替代的4-苯基四氢异喹啉，其中R1-R8在此被定义。
• 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。