5,6-dichloro-3,4-dihydro-1(2H)-isoquinolinone | 73075-67-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 5,6-dichloro-3,4-dihydro-1(2H)-isoquinolinone
• 英文别名: 5,6-dichloro-3,4-dihydro-2H-isoquinolin-1-one；5,6-Dichloro-1,2,3,4-tetrahydroisoquinolin-1-one
• CAS: 73075-67-9
• 化学式: C₉H₇Cl₂NO
• mdl: MFCD16547721
• 分子量: 216.067
• InChiKey: SBVHUZPHJVYZAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5,6-dichloro-3,4-dihydro-1(2H)-isoquinolinone 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 5,6-dichloro-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Inhibitors of phenylethanolamine N-methyltransferase and epinephrine biosynthesis. 1. Chloro-Substituted 1,2,3,4-tetrahydroisoquinolines

  摘要：

  In a search for inhibitors of epinephrine biosynthesis as potential therapeutic agents, a series of 13 ring-chlorinated 1,2,3,4-tetrahydroisoquinolines was prepared. These compounds were tested initially for their ability to inhibit rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) in vitro. Enzyme-inhibitor dissociation constants, determined for the six most potent members of the series, indicated the following order of decreasing potency: 7,8-Cl2 greater than 6,7,8-Cl3 greater than 7-Cl approximately 5,6,7,8-Cl4 greater than 5,7,8-Cl3. These compounds were subsequently examined for PNMT-inhibiting activity in intact rats and mice. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (13, SK&F 64139) was the most potent member of the series both in vitro and in vivo and is currently undergoing clinical investigation.

  DOI：

  10.1021/jm00179a007
• 作为产物：
  描述：

  3-(2,3-二氯苯基)丙酸 在 三氯化铝 、 氯化亚砜 、 sodium azide 、 N,N-二甲基甲酰胺 作用下， 以 四氯乙烯 、 水 、 丙酮 、 甲苯 为溶剂， 反应 6.17h， 生成 5,6-dichloro-3,4-dihydro-1(2H)-isoquinolinone
  参考文献：
  名称：

  Inhibitors of phenylethanolamine N-methyltransferase and epinephrine biosynthesis. 1. Chloro-Substituted 1,2,3,4-tetrahydroisoquinolines

  摘要：

  In a search for inhibitors of epinephrine biosynthesis as potential therapeutic agents, a series of 13 ring-chlorinated 1,2,3,4-tetrahydroisoquinolines was prepared. These compounds were tested initially for their ability to inhibit rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) in vitro. Enzyme-inhibitor dissociation constants, determined for the six most potent members of the series, indicated the following order of decreasing potency: 7,8-Cl2 greater than 6,7,8-Cl3 greater than 7-Cl approximately 5,6,7,8-Cl4 greater than 5,7,8-Cl3. These compounds were subsequently examined for PNMT-inhibiting activity in intact rats and mice. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (13, SK&F 64139) was the most potent member of the series both in vitro and in vivo and is currently undergoing clinical investigation.

  DOI：

  10.1021/jm00179a007

文献信息

• OXAZOLINE DERIVATIVES
  申请人：Galley Guido

  公开号：US20110112080A1

  公开（公告）日：2011-05-12

  The invention relates to compounds of formula I wherein the definitions of X, R and R 1 are as defined herein. The compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  该发明涉及公式I中的化合物，其中X、R和R1的定义如本文所述。公式I中的化合物对痕量胺相关受体（TAARs）有良好的亲和力，特别是对TAAR1。这些化合物可用于治疗抑郁症、焦虑障碍、躁郁症、注意力缺陷多动障碍（ADHD）、与压力相关的障碍、精神分裂症等精神障碍、帕金森病等神经疾病、阿尔茨海默病等神经退行性疾病、癫痫、偏头痛、高血压、物质滥用和代谢性障碍，如进食障碍、糖尿病、糖尿病并发症、肥胖、血脂异常、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍以及心血管疾病。
• NEW BICYCLIC DIHYDROISOQUINOLINE-1-ONE DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20130143863A1

  公开（公告）日：2013-06-06

  The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A 1 , A 2 , A 3 , A 4 , A 5 and n are as described herein, compositions including the compounds and methods of using the compounds. The compounds are useful, for example, as aldosterone synthase (CYP11B2 or CYP11B1) inhibitors for the treatment or prophylaxis of chronic kidney disease, congestive heart failure, hypertension, primary aldosteronism and Cushing syndrome.

  这项发明提供了具有一般式(I)的新化合物，其中R1、R2、R3、R4、R5、R6、A1、A2、A3、A4、A5和n如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。这些化合物可用作醛固酮合酶（CYP11B2或CYP11B1）抑制剂，用于治疗或预防慢性肾脏疾病、充血性心力衰竭、高血压、原发性醛固酮增多症和库欣综合征。
• Oxazoline derivatives
  申请人：Galley Guido

  公开号：US08354441B2

  公开（公告）日：2013-01-15

  The invention relates to compounds of formula I wherein the definitions of X, R and R1 are as defined herein. The compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及公式I的化合物，其中X、R和R1的定义如本文所述。公式I的化合物对微量胺相关受体（TAARs），特别是TAAR1具有良好的亲和力。这些化合物可用于治疗抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍（ADHD）、与压力相关的疾病、精神疾病（如精神分裂症）、神经疾病（如帕金森病）、神经退行性疾病（如阿尔茨海默病）、癫痫、偏头痛、高血压、物质滥用和代谢性疾病（如进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和同化障碍、体温稳态障碍、睡眠和昼夜节律障碍以及心血管疾病）的治疗。
• [EN] OXAZOLINE DERIVATIVES FOR TREATMENT OF CNS DISORDERS<br/>[FR] DÉRIVÉS D'OXAZOLINE POUR LE TRAITEMENT DE TROUBLES DU SYSTÈME NERVEUX CENTRAL (CNS)
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011057973A9

  公开（公告）日：2012-02-02
• BONDINELL W. E.; CHAPIN F. W.; GIRARD G. R.; KAISER C.; KROG A. J.; PAVLO+, J. MED. CHEM., 1980, 23, NO 5, 506-511
  作者：BONDINELL W. E.、 CHAPIN F. W.、 GIRARD G. R.、 KAISER C.、 KROG A. J.、 PAVLO+

  DOI：——

  日期：——