那高利特 | 88058-88-2

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: 那高利特
• 中文别名: 来赛高里
• 英文名称: (4aR,10bR)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazin-9-ol
• 英文别名: Naxagolide
• CAS: 88058-88-2
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.33
• InChiKey: JCSREICEMHWFAY-HUUCEWRRSA-N

物化性质

• 溶解度：
  DMSO：200 mg/mL（808.64 mM；需要超声波）

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

制备方法与用途

纳沙戈利特，化学名为(+)-PHNO，或称为多巴胺，是一种有效的多巴胺D2受体激动剂。它具有研究帕金森病（PD）的潜力。

反应信息

• 作为反应物：
  描述：

  那高利特 生成 [(4aR,10bR)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazin-9-yl] 2,2-dimethylpropanoate
  参考文献：
  名称：

  JONES, J. H.

  摘要：

  DOI：
• 作为产物：
  描述：

  (+)-trans-9-hydroxy-2,3,4a,5,6,10b-hexahydro-4H-naphth[1,2b][1,4]oxazine 在 咪唑 、 四丁基氟化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 那高利特
  参考文献：
  名称：

  Synthesis of the dopamine D2/D3 receptor agonist (+)-PHNO via supercritical fluid chromatography: preliminary PET imaging study with [3-11C]-(+)PHNO

  摘要：

  Carbon-11 labeled (+)-4-[1-C-11]propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([1-(11)]-(+)-PHNO) is a dopamine D-3-preferring agonist radiopharmaceutical used for medical imaging by positron emission tomography (PET). We report the synthesis of (+)-PHNO using supercritical fluid chromatography for enantiomeric resolution of its norpropyl derivative, HNO, followed by propylation. (+)-HNO was used to prepare the radiolabeling precursor, (+)-trans-4-acetyl-9-triisopropylsilyloxy-2,3,4a,5,6,10b-hexahydro-4H-naphth[1,2b)][1,4]oxazine, in 12 steps. Modifications to the labeling procedure were made to ensure consistent preparation of [3-C-11]-(+)-PHNO via [C-11[CH3I. A preliminary PET imaging study was carried out with this tracer in an attempt to image dopamine receptors in brown adipose tissue (brown fat) in vivo. Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetlet.2013.11.113

文献信息

• [EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089721A1

  公开（公告）日：2016-06-09

  The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及甲基噁唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述化合物在潜在治疗或预防涉及促进睡眠的神经和精神疾病和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及促进睡眠的疾病中的用途。
• HETEROBICYCLIC COMPOUNDS
  申请人：Amgen Inc.

  公开号：US20130225552A1

  公开（公告）日：2013-08-29

  Heterobicyclic compounds of Formula (I): or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.

  Formula (I)的杂环化合物： 或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] COMT INHIBITING METHODS AND COMPOSITIONS<br/>[FR] PROCÉDÉS D'INHIBITION DE LA COMT ET COMPOSITIONS ASSOCIÉES
  申请人：LIEBER INST FOR BRAIN DEV

  公开号：WO2016123576A1

  公开（公告）日：2016-08-04

  The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.

  这些发明包括一种抑制受试者中COMT酶的方法，以及式I的化合物或其药用可接受盐，这些化合物在治疗由COMT介导的各种疾病中有用，包括帕金森病和/或精神分裂症。
• [EN] QUINOLIZIDINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE LA QUINOLIZIDINONE
  申请人：MERCK & CO INC

  公开号：WO2009051715A1

  公开（公告）日：2009-04-23

  The present invention is directed to spiropiperidine compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的螺环哌啶化合物，这些化合物是M1受体阳性变构调节剂，并且在治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍方面有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。