1,4-dioxa-9-azadispiro[4.2.4(8).2(5)]tetradecane | 143040-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 1,4-dioxa-9-azadispiro[4.2.4(8).2(5)]tetradecane
• 英文别名: 1-azaspiro[4.5]decan-8-one ethylene ketal；1,4-Dioxa-9-azadispiro[4.2.4^{8}.2^{5}]tetradecane；9,12-dioxa-4-azadispiro[4.2.48.25]tetradecane
• CAS: 143040-01-1
• 化学式: C₁₁H₁₉NO₂
• 分子量: 197.277
• InChiKey: VFDUBLVHVCAVHJ-UHFFFAOYSA-N

物化性质

• 沸点：
  311.8±42.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4-dioxa-9-azadispiro[4.2.4(8).2(5)]tetradecane 在 盐酸 、 四(三苯基膦)钯 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 生成 7-Methylidene-5-azatricyclo[6.3.1.01,5]dodecan-9-one
  参考文献：
  名称：

  A new synthetic entry to the tricyclic skeleton of FR901483 by palladium-catalyzed cyclization of vinyl bromides with ketone enolates

  摘要：

  A new synthetic entry to the FR901483 core is described. The Pd-mediated cyclization of amino-tethered vinyl halides and ketone enolates from the azaspiro[4.5]decan-8-ones 5 and 10 gives the functionalized 7,10a-methanoperhydropyrrolo[1,2-a]-azocines I and II, respectively. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.09.111
• 作为产物：
  描述：

  3-(8-Nitro-1,4-dioxa-spiro[4.5]dec-8-yl)-propionic acid methyl ester 在 palladium on activated charcoal sodium tetrahydroborate 、 甲酸铵 作用下， 以 溶剂黄146 为溶剂， 生成 1,4-dioxa-9-azadispiro[4.2.4(8).2(5)]tetradecane
  参考文献：
  名称：

  A new synthetic entry to the tricyclic skeleton of FR901483 by palladium-catalyzed cyclization of vinyl bromides with ketone enolates

  摘要：

  A new synthetic entry to the FR901483 core is described. The Pd-mediated cyclization of amino-tethered vinyl halides and ketone enolates from the azaspiro[4.5]decan-8-ones 5 and 10 gives the functionalized 7,10a-methanoperhydropyrrolo[1,2-a]-azocines I and II, respectively. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.09.111

文献信息

• [EN] AZASPIROALKENE AND AZASPIROALKANE COMPOUNDS WITH NICOTINIC CHOLINERGIC RECEPTOR ACTIVITY<br/>[FR] COMPOSES D'AZASPIROALCENE ET D'AZASPIROALCANE A ACTIVITE DE RECEPTEURS NICOTINIQUES CHOLINERGIQUES
  申请人：TARGACEPT INC

  公开号：WO2006034089A1

  公开（公告）日：2006-03-30

  Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are N-aryl or heteroaryl azaspiroalkene/alkane compounds, prodrugs or metabolites of these compounds, or pharmaceutically acceptable salts thereof. The aryl group can be a phenyl ring or a five- or six-membered heterocyclic ring (heteroaryl). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds and compositions can also be used to alleviate pain. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

  揭示了化合物、包括这些化合物的药物组合物以及其制备和使用方法。这些化合物是N-芳基或杂环芳基氮杂螺环烯/烷化合物，这些化合物的前药或代谢物，或其药用可接受的盐。芳基可以是苯环或五元或六元杂环环（杂环芳基）。这些化合物和组合物可用于治疗和/或预防各种各样的疾病或紊乱，特别是那些以胆碱能神经递质功能障碍为特征的疾病，包括涉及神经递质释放的神经调节紊乱，如多巴胺释放的疾病。中枢神经系统疾病，其特征是正常神经递质释放的改变，是可以治疗和/或预防的另一个例子。这些化合物和组合物也可用于缓解疼痛。这些化合物可以：（i）改变患者大脑中的胆碱能受体数量，（ii）表现出神经保护作用，以及（iii）在有效剂量下使用时，不会导致明显的不良副作用（例如，明显增加血压和心率、对胃肠道产生明显负面影响，以及对骨骼肌产生明显影响）。
• N-aryl azaspiroalkene and azaspiroalkane compounds and methods of preparation and use thereof
  申请人：Bhatti Balwinder

  公开号：US20060074067A1

  公开（公告）日：2006-04-06

  Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are N-aryl or heteroaryl azaspiroalkene/alkane compounds, prodrugs or metabolites of these compounds, or pharmaceutically acceptable salts thereof. The aryl group can be a phenyl ring or a five- or six-membered heterocyclic ring (heteroaryl). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds and compositions can also be used to alleviate pain. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

  本文揭示了化合物、包括这些化合物的制药组合物及其制备和使用方法。这些化合物是N-芳基或杂芳基氮杂螺环烯/烷化合物、这些化合物的前药或代谢物，或其药学上可接受的盐。芳基可以是苯环或五元或六元杂环环（杂芳基）。这些化合物和组合物可用于治疗和/或预防各种疾病或障碍，特别是那些以尼古丁型乙酰胆碱神经递质功能障碍为特征的障碍，包括涉及神经递质释放的神经调节障碍，如多巴胺释放。中枢神经系统障碍是另一种可以治疗和/或预防的障碍，其特征是正常神经递质释放的改变。这些化合物和组合物也可用于缓解疼痛。这些化合物可以：（i）改变患者大脑中尼古丁型乙酰胆碱受体的数量，（ii）表现出神经保护作用，（iii）当以有效量使用时，不会产生明显的不良副作用（例如，明显增加血压和心率、对胃肠道产生明显的负面影响和对骨骼肌产生显著影响等副作用）。
• N-ARYL AZASPIROALKENE AND AZASPIROALKANE COMPOUNDS AND METHODS OF PREPARATION AND USE THEREOF
  申请人：Bhatti Balwinder

  公开号：US20080242689A1

  公开（公告）日：2008-10-02

  Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are N-aryl or heteroaryl azaspiroalkene/alkane compounds, prodrugs or metabolites of these compounds, or pharmaceutically acceptable salts thereof. The aryl group can be a phenyl ring or a five- or six-membered heterocyclic ring (heteroaryl). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds and compositions can also be used to alleviate pain. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

  本发明揭示了化合物、包括这些化合物的药物组合物的制备方法和使用方法。这些化合物是N-芳基或杂芳基氮杂螺环烯/烷化合物、这些化合物的前药或代谢物，或其药学上可接受的盐。芳基可以是苯环或五元或六元杂环环（杂芳基）。这些化合物和组合物可用于治疗和/或预防各种疾病或疾病，特别是那些以尼古丁性胆碱能神经递质功能障碍为特征的疾病，包括涉及神经递质释放的神经调节疾病，如多巴胺释放。中枢神经系统疾病，其特征是正常神经递质释放的改变，是可以治疗和/或预防的另一个例子。这些化合物和组合物也可用于缓解疼痛。这些化合物可以：（i）改变患者的脑部尼古丁性胆碱能受体数量，（ii）表现出神经保护作用，（iii）当以有效剂量使用时，不会产生明显的不良副作用（例如，明显增加血压和心率、对胃肠道产生明显的负面影响以及对骨骼肌产生明显的影响等副作用）。
• Compounds for Treating Disorders Mediated by Metabotropic Glutamate Receptor 5, and Methods of Use Thereof
  申请人：Hardy Larry Wendell

  公开号：US20110319380A1

  公开（公告）日：2011-12-29

  Provided herein are compounds and methods of synthesis thereof. The compounds set forth herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders, neurodegenerative disorders, neuropsychiatric disorders, disorders of cognition, learning or memory, gastrointestinal disorders, lower urinary tract disorder, and cancer. Compounds set forth herein modulate the activity of metabotropic glutamate receptor 5 (mGluR5) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

  本文提供了化合物及其合成方法。本文中提供的化合物可用于治疗、预防和/或管理各种疾病，如神经系统疾病、神经退行性疾病、神经精神疾病、认知、学习或记忆障碍、胃肠道疾病、下尿路障碍和癌症。本文提供的化合物在中枢神经系统或外周调节代谢性谷氨酸受体5(mGluR5)的活性。本文还提供了含有这些化合物的药物制剂及其使用方法。
• COMPOUNDS FOR TREATING DISORDERS MEDIATED BY METABOTROPIC GLUTAMATE RECEPTOR 5, AND METHODS OF USE THEREOF
  申请人：Sunovion Pharmaceuticals Inc.

  公开号：US20140349992A1

  公开（公告）日：2014-11-27

  Provided herein are compounds and methods of synthesis thereof. The compounds set forth herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders, neurodegenerative disorders, neuropsychiatric disorders, disorders of cognition, learning or memory, gastrointestinal disorders, lower urinary tract disorder, and cancer. Compounds set forth herein modulate the activity of metabotropic glutamate receptor 5 (mGluR5) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

  本文提供了化合物及其合成方法。这些化合物可用于治疗、预防和/或管理各种疾病，如神经疾病、神经退行性疾病、神经精神疾病、认知、学习或记忆障碍、胃肠道疾病、下尿路障碍和癌症等。本文提供的化合物在中枢神经系统或外周调节代谢性谷氨酸受体5 (mGluR5) 的活性。本文还提供了含有这些化合物的药物制剂及其使用方法。