(R)-8 trifluoromethyl-1,2,3,4,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-6-one | 850037-28-4

• 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: (R)-8 trifluoromethyl-1,2,3,4,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-6-one
• 英文别名: (11aR)-8-(trifluoromethyl)-1,2,3,4,11,11a-hexahydropyrazino[1,2-b]isoquinolin-6-one
• CAS: 850037-28-4
• 化学式: C₁₃H₁₃F₃N₂O
• 分子量: 270.254
• InChiKey: KGYOIHNXJRJXJD-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-8 trifluoromethyl-1,2,3,4,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-6-one 、 N-溴代丁二酰亚胺(NBS) 在 碳酸氢钠 、 乙酸乙酯 、 Sodium sulfate-III 、 SiO2 、 dichloromethane MeOH Et3N 作用下， 以 硫酸 为溶剂， 反应 48.0h， 以provided (R)-10-bromo-8-trifluoromethyl-1,2,3,4,11,11a-hexahydropyrazino[1,2-b]isoquinolin-6-one (80 mg, 25%) as an off-white solid的产率得到(R)-10-bromo-8-trifluoromethyl-1,2,3,4,11,11a-hexahydropyrazino[1,2-b]isoquinolin-6-one
  参考文献：
  名称：

  Modulators of serotonin receptors

  摘要：

  本发明提供了选择性调节血清素受体的调节剂，包括药物组合物和治疗各种疾病、状况和与血清素受体调节相关的障碍的方法。这些疾病、状况和障碍包括但不限于代谢性疾病，如肥胖症、糖尿病、糖尿病并发症、动脉硬化、糖耐量受损和血脂异常；中枢神经系统疾病，如焦虑、抑郁、强迫症、惊恐障碍、精神病、精神分裂症、睡眠障碍、性功能障碍和社交恐惧症；头痛；偏头痛；以及使用这些化合物和组合物治疗胃肠道疾病。

  公开号：

  US07244843B2
• 作为产物：
  描述：

  (3R)-1-Benzyl-3-(4-trifluoromethylbenzyl)piperazine 在 吡啶 、 四磷十氧化物 、 palladium 10% on activated carbon 、 氢气 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 生成 (R)-8 trifluoromethyl-1,2,3,4,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-6-one
  参考文献：
  名称：

  Synthesis and SAR of potent and selective tetrahydropyrazinoisoquinolinone 5-HT2C receptor agonists

  摘要：

  The 5-HT2C receptor has been implicated as a critical regulator of appetite. Small molecule activation of the 5-HT2C receptor has been shown to affect food intake and regulate body weight gain in rodent models and more recently in human clinical trials. Therefore, 5-HT2C is a well validated target for anti-obesity therapy. The synthesis and structure-activity relationships of a series of novel tetrahydropyrazinoisoquinolinone 5-HT2C receptor agonists are presented. Several members of this series were identified as potent 5-HT2C receptor agonists with high functional selectivity against the 5-HT2A and 5-HT2B receptors and reduced food intake in an acute rat feeding model upon oral dosing. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.061

文献信息

• MODULATORS OF SEROTONIN RECEPTORS
  申请人：Wacker A. Dean

  公开号：US20070213337A1

  公开（公告）日：2007-09-13

  The present invention provides modulators of serotonin receptors, pharmaceutical compositions containing such modulators and methods for treating various diseases, conditions and disorders associated with modulation of serotonin receptors such as, for example: metabolic diseases, which includes but is not limited to obesity, diabetes, diabetic complications, atherosclerosis, impaired glucose tolerance and dyslipidemia; central nervous system diseases which includes but is not limited to, anxiety, depression, obsessive compulsive disorder, panic disorder, psychosis, schizophrenia, sleep disorder, sexual disorder and social phobias; cephalic pain; migraine; and gastrointestinal disorders using such compounds and compositions.

  本发明提供了5-羟色胺受体调节剂，包含这种调节剂的药物组合物以及使用这些化合物和组合物治疗与5-羟色胺受体调节相关的各种疾病、病况和障碍的方法，例如：代谢性疾病，包括但不限于肥胖症、糖尿病、糖尿病并发症、动脉粥样硬化、糖耐量受损和血脂异常；中枢神经系统疾病，包括但不限于焦虑、抑郁、强迫症、惊恐障碍、精神病、精神分裂症、睡眠障碍、性功能障碍和社交恐惧症；头痛；偏头痛；和使用这些化合物和组合物治疗胃肠道疾病。
• US7244843B2
  申请人：——

  公开号：US7244843B2

  公开（公告）日：2007-07-17
• US7812024B2
  申请人：——

  公开号：US7812024B2

  公开（公告）日：2010-10-12
• Synthesis and SAR of potent and selective tetrahydropyrazinoisoquinolinone 5-HT2C receptor agonists
  作者：Guohua Zhao、Chet Kwon、Sharon N. Bisaha、Philip D. Stein、Karen A. Rossi、Xueying Cao、Thao Ung、Ginger Wu、Chen-Pin Hung、Sarah E. Malmstrom、Ge Zhang、Qinling Qu、Jinping Gan、William J. Keim、Mary Jane Cullen、Kenneth W. Rohrbach、James Devenny、Mary Ann Pelleymounter、Keith J. Miller、Jeffrey A. Robl

  DOI：10.1016/j.bmcl.2013.04.061

  日期：2013.7

  The 5-HT2C receptor has been implicated as a critical regulator of appetite. Small molecule activation of the 5-HT2C receptor has been shown to affect food intake and regulate body weight gain in rodent models and more recently in human clinical trials. Therefore, 5-HT2C is a well validated target for anti-obesity therapy. The synthesis and structure-activity relationships of a series of novel tetrahydropyrazinoisoquinolinone 5-HT2C receptor agonists are presented. Several members of this series were identified as potent 5-HT2C receptor agonists with high functional selectivity against the 5-HT2A and 5-HT2B receptors and reduced food intake in an acute rat feeding model upon oral dosing. (c) 2013 Elsevier Ltd. All rights reserved.
• Modulators of serotonin receptors
  申请人：Wacker A. Dean

  公开号：US20050080074A1

  公开（公告）日：2005-04-14

  The present invention provides modulators of serotonin receptors, pharmaceutical compositions containing such modulators and methods for treating various diseases, conditions and disorders associated with modulation of serotonin receptors such as, for example: metabolic diseases, which includes but is not limited to obesity, diabetes, diabetic complications, atherosclerosis, impared glucose tolerance and dyslipidemia; central nervous system diseases which includes but is not limited to, anxiety, depression, obsessive compulsive disorder, panic disorder, psychosis, schizophrenia, sleep disorder, sexual disorder and social phobias; cephalic pain; migraine; and gastrointestinal disorders using such compounds and compositions.

  本发明提供了调节血清素受体的调节剂，包含这种调节剂的药物组合物以及使用这些化合物和组合物治疗与调节血清素受体相关的各种疾病、状况和障碍的方法，例如：代谢性疾病，包括但不限于肥胖症、糖尿病、糖尿病并发症、动脉粥样硬化、糖耐量受损和血脂异常；中枢神经系统疾病，包括但不限于焦虑、抑郁、强迫症、恐慌症、精神病、精神分裂症、睡眠障碍、性功能障碍和社交恐惧症；头痛；偏头痛；以及使用这些化合物和组合物治疗胃肠道疾病。