5-bromo-1-[1,4-dioxa-spiro[4.5]dec-8-yl]-1H-indole | 1221280-17-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-bromo-1-[1,4-dioxa-spiro[4.5]dec-8-yl]-1H-indole
• 英文别名: 5-bromo-1-(1,4-dioxa-spiro[4.5]dec-8-yl)-1H-indole；5-bromo-1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-indole；5-bromo-1-(1,4-dioxaspiro[4.5]decan-8-yl)indole
• CAS: 1221280-17-6
• 化学式: C₁₆H₁₈BrNO₂
• 分子量: 336.228
• InChiKey: WMGMZKSVFPXVHT-UHFFFAOYSA-N

物化性质

• 沸点：
  473.3±45.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  23.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1-[1,4-dioxa-spiro[4.5]dec-8-yl]-1H-indole 在 sodium tetrahydroborate 、 水 、 对甲苯磺酸 作用下， 以 甲醇 、 丙酮 、 mineral oil 为溶剂， 反应 0.33h， 生成 4-(5-bromoindol-1-yl)cyclohexanol
  参考文献：
  名称：

  Imidazo[1,2-a]pyridines: Orally Active Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor

  摘要：

  Advanced leads of an imidazopyridine series of positive allosteric modulators of the metabotropic glutamate 2 (mGlu2) receptor are reported. The optimization of in vitro ADMET and in vivo pharmacokinetic properties led to the identification of 27o. With good potency and selectivity for the mGlu2 receptor, 270 affected sleep-wake architecture in rats after oral treatment, which we have previously shown to be indicative of mGlu2 receptor-mediated central activity.

  DOI：

  10.1021/jm201561r
• 作为产物：
  描述：

  5-溴吲哚 、 1,4-二氧杂螺[4.5]癸-8-基4-甲基苯磺酸酯 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 以19.93%的产率得到5-bromo-1-[1,4-dioxa-spiro[4.5]dec-8-yl]-1H-indole
  参考文献：
  名称：

  [EN] 1,2,4-TRIAZOLO[4,3-A]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
  [FR] DÉRIVÉS DE LA 1,2,4-TRIAZOLO [4,3-A] PYRIDINE ET LEUR UTILISATION EN TANT QUE MODULATEURS ALLOSTÉRIQUES POSITIFS DES RÉCEPTEURS MGLUR2

  摘要：

  本发明涉及新型三唑并[4,3-a]吡啶衍生物的公式(I)，其中所有基团如权利要求中所定义。根据本发明的化合物是代谢型谷氨酸受体亚型2（"mGluR2"）的阳性变构调节剂，对于治疗或预防与谷氨酸功能障碍相关的神经和精神疾病以及代谢型受体的mGluR2亚型参与的疾病具有用处。本发明还涉及包括这种化合物的药物组合物，用于制备这种化合物和组合物的方法，以及利用这种化合物预防或治疗与mGluR2有关的神经和精神疾病和疾病。

  公开号：

  WO2010130422A1

文献信息

• [EN] 1,2,4-TRIAZOLO[4,3-A]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS<br/>[FR] DÉRIVÉS DE LA 1,2,4-TRIAZOLO [4,3-A] PYRIDINE ET LEUR UTILISATION EN TANT QUE MODULATEURS ALLOSTÉRIQUES POSITIFS DES RÉCEPTEURS MGLUR2
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2010130422A1

  公开（公告）日：2010-11-18

  The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

  本发明涉及新型三唑并[4,3-a]吡啶衍生物的公式(I)，其中所有基团如权利要求中所定义。根据本发明的化合物是代谢型谷氨酸受体亚型2（"mGluR2"）的阳性变构调节剂，对于治疗或预防与谷氨酸功能障碍相关的神经和精神疾病以及代谢型受体的mGluR2亚型参与的疾病具有用处。本发明还涉及包括这种化合物的药物组合物，用于制备这种化合物和组合物的方法，以及利用这种化合物预防或治疗与mGluR2有关的神经和精神疾病和疾病。
• [EN] INDOLE AND BENZOXAZINE DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] DÉRIVÉS D'INDOLE ET DE BENZOXAZINE COMME MODULATEURS DES RÉCEPTEURS MÉTABOTROPIQUES AU GLUTAMATE
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2010060589A1

  公开（公告）日：2010-06-03

  The present invention relates to novel indole and benzoxazine derivatives which are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2") and which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

  本发明涉及新型吲哚和苯并噁嗪衍生物，它们是代谢型谷氨酸受体亚型2（"mGluR2"）的正向变构调节剂，用于治疗或预防与谷氨酸功能障碍相关的神经和精神疾病，以及涉及代谢型受体亚型mGluR2的疾病。该发明还涉及包含这些化合物的药物组合物，用于制备这些化合物和组合物的过程，以及利用这些化合物预防或治疗涉及mGluR2的神经和精神疾病和疾病。
• [EN] INDOLE AND BENZOMORPHOLINE DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] DÉRIVÉS D'INDOLE ET DE BENZOMORPHOLINE EN TANT QUE MODULATEURS DES RÉCEPTEURS MÉTABOTROPIQUES DU GLUTAMATE
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2010043396A1

  公开（公告）日：2010-04-22

  The present invention relates to novel compounds, in particular novel indole and benzomorpholine derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors - subtype 2 ("mGluR2") which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新颖化合物，特别是根据式(I)的新型吲哚和苯并吗啡啉衍生物，其中所有基团如申请和索赔中所定义。根据本发明的化合物是代谢型受体-亚型2（"mGluR2"）的阳性变构调节剂，对于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及涉及代谢型受体中mGluR2亚型的疾病是有用的。特别是，这些疾病是来自焦虑、精神分裂症、偏头痛、抑郁症和癫痫的中枢神经系统疾病。该发明还涉及制备这种化合物和组合物的药物组合物和过程，以及利用这种化合物预防和治疗涉及mGluR2的这些疾病。
• INDOLE AND BENZOXAZINE DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Cid-Nunez Jose Maria

  公开号：US20120035167A1

  公开（公告）日：2012-02-09

  The present invention relates to novel indole and benzoxazine derivatives which are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 (“mGluR2”) and which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

  本发明涉及新型吲哚和苯并噁嗪衍生物，其为代谢型谷氨酸受体亚型2（“mGluR2”）的正向变构调节剂，并且对于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及涉及代谢型受体亚型mGluR2的疾病具有用途。本发明还涉及包含这些化合物的制药组合物，制备这些化合物和组合物的过程以及使用这些化合物预防或治疗涉及mGluR2的神经和精神障碍和疾病。
• INDOLE AND BENZOMORPHOLINE DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Cid-Nunez Jose Maria

  公开号：US20110275624A1

  公开（公告）日：2011-11-10

  The present invention relates to novel compounds, in particular novel indole and benzomorpholine derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及一种新型化合物，特别是根据公式（I）中定义的所有基团的新型吲哚和苯并吗啡衍生物。本发明的化合物是代谢型受体亚型2（“mGluR2”）的正向变构调节剂，可用于治疗或预防与谷氨酸功能障碍有关的神经和精神障碍以及涉及代谢型受体亚型2的疾病。特别是，这些疾病是从焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病中选择的。本发明还涉及制备这种化合物和组合物的制药组合物和制备过程，以及使用这种化合物预防和治疗涉及mGluR2的这些疾病。