4-氟-4-苯基哌啶盐酸盐 | 1056382-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-氟-4-苯基哌啶盐酸盐
• 英文名称: 4-fluoro-4-phenylpiperidine hydrochloride
• 英文别名: 4-fluoro-4-phenylpiperidine;hydrochloride
• CAS: 1056382-25-2
• 化学式: C₁₁H₁₄FN*ClH
• mdl: MFCD13176614
• 分子量: 215.698
• InChiKey: YKHBLOUKDHUYIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.66
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  12
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-氟-4-苯基哌啶盐酸盐 在 一水合肼 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 17.33h， 生成 8-chloro-7-(4-fluoro-4-phenyl-1-piperidinyl)-3-(2,2,2-trifluoroethyl)-1,2,4-triazolo[4,3-a]pyridine
  参考文献：
  名称：

  Discovery of 3-Cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): A Positive Allosteric Modulator of the Metabotropic Glutamate 2 Receptor

  摘要：

  Advanced leads from a series of 1,2,4-triazolo[4,3-a]pyridines with mGlu2 receptor PAM activity are reported. By modification of the analogous imidazo[1,2-a]pyridine series, the newly reported leads have improved potency, in vitro ADMET, and hERG as well as good in vivo PK profile. The optimization of the series focused on improving metabolic stability while controlling lipophilicity by introducing small modifications to the scaffold substituents. Analysis of this series combined with our previously reported mGlu2 receptor PAMs showed how lipophilic ligand efficiency was improved during the course of the program. Among the best compounds, example 20 (JNJ-42153605) showed a central in vivo efficacy by inhibition of REM sleep state at a dose of 3 mg/kg po in the rat sleep-wake EEG paradigm, a phenomenon shown earlier to be mGlu2 mediated. In mice, compound 20 reversed PCP-induced hyperlocomotion with an ED50 of 5.4 mg/kg sc, indicative of antipsychotic activity.

  DOI：

  10.1021/jm3010724
• 作为产物：
  描述：

  4-氟-4-苯基哌啶-1-羧酸叔丁酯 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以97%的产率得到4-氟-4-苯基哌啶盐酸盐
  参考文献：
  名称：

  [EN] 1',3'-DISUBSTITUTED-4-PHENYL-3,4,5,6-TETRAHYDRO-2H, 1'H-[1, 4'] BIPYRIDINYL-2'-ONES
  [FR] 4-PHÉNYL-3,4,5,6-TÉTRAHYDRO-2H,1'H-[1, 4'] BIPYRIDINYL-2'-ONES 1', 3'-DISUSBSTITUÉES

  摘要：

  本发明涉及新型化合物，特别是根据式（I）中定义的新型吡啶酮衍生物，其中所有基团均如申请和权利要求中所定义。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，用于治疗或预防与谷氨酸功能障碍相关的神经系统和精神疾病，以及mGluR2代谢型受体亚型涉及的疾病。具体来说，这些疾病是来自焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病的选择性疾病。本发明还涉及制备这种化合物和组合物的药物组合物和方法，以及利用这种化合物预防和治疗mGluR2涉及的疾病。

  公开号：

  WO2009033704A1

文献信息

• 3-CYANO-4-(4-PHENYL-PIPERIDIN-1-YL)-PYRIDIN-2-ONE DERIVATIVES
  申请人：Cid-Núñez José Maria

  公开号：US20100063092A1

  公开（公告）日：2010-03-11

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) including any stereochemically isomeric form thereof, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic glutamate 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 such compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新型化合物，特别是根据公式（I）的新型吡啶酮衍生物，包括其任何立体化异构体形式、药学上可接受的盐或其溶剂化物，其中所有基团在申请和权利要求中均有定义。本发明所述化合物是代谢型谷氨酸受体亚型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相关的神经和精神障碍以及涉及代谢型受体mGluR2亚型的疾病。特别是，这些疾病是选择自焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病的一组。本发明还涉及制备这种化合物和这种组合物的制药组合物和过程，以及将这种化合物用于预防和治疗涉及mGluR2的这种疾病。
• 1,3-DISUBSTITUTED-4-PHENYL-3,4,5,6-TETRAHYDRO-2H,1 H-1,4 BIPYRIDINYL-2-ONES
  申请人：Cid-Nunez Jose Maria

  公开号：US20100240688A1

  公开（公告）日：2010-09-23

  The present invention relates to novel compounds, in particular novel pyridinone 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，特别是公式（I）中所示的新型吡啶酮衍生物，其中所有基团均如申请和权利要求中所定义。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mGluR2亚型的疾病。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，以及利用这种化合物预防和治疗涉及mGluR2的这些疾病的用途。
• 1,2,3-TRIAZOLO [4,3-A] PYRIDINE DERIVATIVES AND THIER USE FOR THE TREATMENT OF PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
  申请人：Cid-Nunez Jose Maria

  公开号：US20120184525A1

  公开（公告）日：2012-07-19

  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.

  本发明涉及一种新型的三唑并[4,3-a]吡啶衍生物，其化学式为（I），其中所有基团均如权利要求中所定义。本发明中的化合物是代谢型谷氨酸受体亚型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的mGluR2亚型的疾病。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的方法。
• 1',3'-DISUBSTITUTED-4-PHENY-3,4,5,6-TETRAHYDRO-2H,1'H-[1,4']BIPYRIDINYL-2'-ONES
  申请人：CID-NUNEZ Jose Maria

  公开号：US20130196992A1

  公开（公告）日：2013-08-01

  The present invention relates to novel compounds, in particular novel pyridinone 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.

  本发明涉及新型化合物，特别是公式（I）中所示的新型吡啶酮衍生物，其中所有基团均如本申请和权利要求中所定义。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和mGluR2代谢型受体有关的神经和精神障碍以及相关疾病。特别地，这些疾病是选择自焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病的群体。本发明还涉及制备这种化合物和组合物的制药组合物和过程，以及利用这种化合物预防和治疗涉及mGluR2的这些疾病的用途。
• 1,2,4-Triazolo [4,3-A] Pyridine Derivatives and Their Use For The Treatment of Prevention of Neurological and Psychiatric Disorders
  申请人：JANSSEN PHARMACEUTICALS, INC.

  公开号：US20150141403A1

  公开（公告）日：2015-05-21

  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.

  本发明涉及一种新型的三唑并[4,3-a]吡啶衍生物，其化学式为（I），其中所有基团如权利要求所定义。本发明的化合物是代谢型谷氨酸受体亚型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。本发明还涉及包含这种化合物的制药组合物、制备这种化合物和组合物的过程，以及使用这种化合物预防或治疗涉及mGluR2的神经和精神障碍和疾病的方法。