JNJ-46281222 | 1254980-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: JNJ-46281222
• 英文别名: 3-(cyclopropylmethyl)-7-[(4-phenyl-1-piperidinyl)methyl]-8-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyridine；3-(Cyclopropylmethyl)-7-[(4-phenylpiperidin-1-yl)methyl]-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine
• CAS: 1254980-38-5
• 化学式: C₂₃H₂₅F₃N₄
• 分子量: 414.474
• InChiKey: LYDKDODJIBQNLK-UHFFFAOYSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  33.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  JNJ-46281222 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 以82%的产率得到3-(cyclopropylmethyl)-7-[(4-phenyl-1-piperidinyl)methyl]-8-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyridine hydrochloride
  参考文献：
  名称：

  [EN] 1,2,4-TRIAZOLO [4,3-A] PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OR PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
  [FR] DÉRIVÉS DE 1,2,3-TRIAZOLO[4,3-A]PYRIDINE ET LEUR UTILISATION POUR LE TRAITEMENT OU LA PRÉVENTION DE TROUBLES NEUROLOGIQUES ET PSYCHIATRIQUES

  摘要：

  公开号：

  WO2010130424A9
• 作为产物：
  描述：

  7-vinyl-3-(cyclopropylmethyl)-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine 在 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 9.0h， 生成 JNJ-46281222
  参考文献：
  名称：

  Discovery of 8-Trifluoromethyl-3-cyclopropylmethyl-7-[(4-(2,4-difluorophenyl)-1-piperazinyl)methyl]-1,2,4-triazolo[4,3-a]pyridine (JNJ-46356479), a Selective and Orally Bioavailable mGlu2 Receptor Positive Allosteric Modulator (PAM)

  摘要：

  Positive allosteric modulators of the metabotropic glutamate 2 receptor have generated great interest in the past decade. There is mounting evidence of their potential as therapeutic agents in the treatment of multiple central nervous system disorders: We have previously reported substantial efforts leading to potent and selective mGlu2 PAMs. However, finding compounds with the optimal combination of in vitro potency and good druglike properties has remained elusive, in part because of the hydrophobic nature of the allosteric binding site. Herein, we report on the lead optimization process to overcome the poor solubility inherent to the advanced lead 6. Initial prototypes already showed significant improvements in Solubility while retaining good functional activity but displayed new liabilities associated with metabolism and hERG inhibition. Subsequent subtle modifications efficiently addressed those issues leading to the identification of compound 27 (JNJ-46356479). This new lead represents a more balanced profile that offers a significant improvement on the druglike attributes compared to previously reported leads.

  DOI：

  10.1021/acs.jmedchem.6b00913

文献信息

• [EN] COMBINATIONS COMPRISING POSITIVE ALLOSTERIC MODULATORS OR ORTHOSTERIC AGONISTS OF METABOTROPIC GLUTAMATERGIC RECEPTOR SUBTYPE 2 AND THEIR USE<br/>[FR] COMBINAISONS COMPRENANT DES MODULATEURS ALLOSTÉRIQUES POSITIFS OU DES AGONISTES ORTHOSTÉRIQUES DE SOUS-TYPE 2 DE RÉCEPTEUR GLUTAMATERGIQUE MÉTABOTROPE, ET LEUR UTILISATION
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2015110435A1

  公开（公告）日：2015-07-30

  The present invention relates to combinations comprising a positive allosteric modulator ("PAM") of metabotropic glutamatergic receptor subtype 2 ("mGluR2") or a pharmaceutically acceptable salt or a solvate thereof, or an orthosteric agonist of metabotropic glutamatergic receptor subtype 2 compound or a pharmaceutically acceptable salt or a solvate thereof, and a synaptic vesicle protein 2A ("SV2A") ligand.

  本发明涉及组合物，包括一种代谢型谷氨酸受体亚型2（"mGluR2"）的正向变构调节剂（"PAM"）或其药用可接受盐或溶剂，或一种代谢型谷氨酸受体亚型2的正交合激动剂化合物或其药用可接受盐或溶剂，以及突触囊泡蛋白2A（"SV2A"）配体。
• 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。
• 1,2,4-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。
• COMBINATIONS COMPRISING POSITIVE ALLOSTERIC MODULATORS OR ORTHOSTERIC AGONISTS OF METABOTROPIC GLUTAMATERGIC RECEPTOR SUBTYPE 2 AND THEIR USE
  申请人：Janssen Pharmaceutica NV

  公开号：EP3424535A1

  公开（公告）日：2019-01-09

  The present invention relates to combinations comprising a positive allosteric modulator ("PAM") of metabotropic glutamatergic receptor subtype 2 ("mGluR2") or a pharmaceutically acceptable salt or a solvate thereof, or an orthosteric agonist of metabotropic glutamatergic receptor subtype 2 compound or a pharmaceutically acceptable salt or a solvate thereof, and a synaptic vesicle protein 2A ("SV2A") ligand.

  本发明涉及由代谢谷氨酸能受体亚型 2（"mGluR2"）的正异位调节剂（"PAM"）或其药学上可接受的盐或溶液，或代谢谷氨酸能受体亚型 2 化合物的正异位激动剂或其药学上可接受的盐或溶液和突触囊泡蛋白 2A（"SV2A"）配体组成的组合。
• 1,2,4-triazolo [4,3-A] pyridine derivatives and their use for the treatment of neurological and psychiatric disorders
  申请人：JANSSEN PHARMACEUTICALS, INC.

  公开号：US10071095B2

  公开（公告）日：2018-09-11

  The present invention relates to methods of treating various central nervous system disorders using 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.

  本发明涉及使用式 (I) 的新型三唑并[4,3-a]吡啶衍生物治疗各种中枢神经系统疾病的方法 其中所有基团如权利要求中定义。根据本发明的化合物是代谢型谷氨酸受体亚型 2（"mGluR2"）的正异位调节剂，可用于治疗或预防与谷氨酸功能障碍相关的神经和精神疾病以及代谢型受体 mGluR2 亚型参与的疾病。本发明还涉及包含此类化合物的药物组合物、制备此类化合物和组合物的工艺，以及使用此类化合物预防或治疗涉及 mGluR2 的神经和精神障碍及疾病。