6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline | 543738-41-6

• 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: 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 6,8-dichloro-2-methyl-4-phenyl-3,4-dihydro-1H-isoquinoline
• CAS: 543738-41-6
• 化学式: C₁₆H₁₅Cl₂N
• 分子量: 292.208
• InChiKey: SHBPZIGBKLSQFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline 在 氯磺酸 作用下， 以 二氯甲烷 、 氨 为溶剂， 生成 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide
  参考文献：
  名称：

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

  摘要：

  本发明涉及式I1的新化合物，其中R1至R10 R7的定义如本文所述。在一种实施方式中，这些化合物可以用作降压剂，用于减少或预防缺血引起的损伤，作为治疗神经系统缺血、中风和脑水肿、休克、呼吸驱动力受损的外科干预药物，用于治疗打鼾、作为泻药、抗外寄生虫剂、预防胆石形成、抗动脉粥样硬化、治疗糖尿病晚期并发症、癌症、纤维化疾病、内皮功能障碍、器官肥大和增生的药物。在另一种实施方式中，这些化合物可以是细胞钠-质子抗转运体的抑制剂，影响血清脂蛋白，因此可用于治疗动脉粥样硬化病变。

  公开号：

  US20030171580A1
• 作为产物：
  描述：

  2-((2,4-dichlorobenzyl)(methyl)amino)-1-phenylethanol 在 硫酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 以50%的产率得到6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  [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
  [FR] COMPOSÉS ET PROCÉDÉS D'INHIBITION D'UN ANTIPORT À MÉDIATION PAR NHE DANS LE TRAITEMENT DE TROUBLES ASSOCIÉS À UNE RÉTENTION DE FLUIDE OU À UNE SURCHARGE DE SEL ET DE TROUBLES DU TRACTUS GASTRO-INTESTINAL

  摘要：

  公开号：

  WO2010078449A3

文献信息

• Substituted 4-phenyltetrahydroisoquinolinium, process for their preparation, their use as a medicament, and medicament containing them
  申请人：Hofmeister Armin

  公开号：US20050009864A1

  公开（公告）日：2005-01-13

  The invention relates to compounds of the formula I in which R1 to R9 are as defined herein. In one embodiment, these compounds may be used as antihypertensives, for reducing or preventing ischemia-induced damage, as medicaments for surgical intervention for the treatment of ischemias of the nervous system, of stroke and of cerebral edema, of shock, of impaired respiratory drive, for the treatment of snoring, as laxative, as agent against ectoparasites, to prevent the formation of gallstones, as antiatherosclerotics, agents against late complications of diabetes, cancers, fibrotic disorders, endothelial dysfunction, organ hypertrophies and hyperplasias. In one embodiment, the compounds may be inhibitors of the cellular sodium-proton antiporter and influence serum lipoproteins and thus be used for the prophylaxis and for the regression of atherosclerotic lesions.

  本发明涉及公式I中R1至R9所定义的化合物。在一种实施例中，这些化合物可用作降压药、用于减少或预防缺血引起的损伤、作为治疗神经系统缺血、中风和脑水肿、休克、呼吸驱动力受损、打鼾的药物、作为泻药、对抗外寄生虫的药物、预防胆石形成、作为抗动脉粥样硬化药物、对抗糖尿病晚期并发症、癌症、纤维化疾病、内皮功能障碍、器官肥大和增生的药物。在一种实施例中，这些化合物可以是细胞钠-质子抗转运体的抑制剂，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。
• 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。