3-chloro-1-isobutyl-4-(4-phenyl-1-piperidyl)pyridin-2-one | 1127498-55-8

• 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: 3-chloro-1-isobutyl-4-(4-phenyl-1-piperidyl)pyridin-2-one
• 英文别名: 3-Chloro-1-(2-methylpropyl)-4-(4-phenyl-1-piperidinyl)-2(1H)-pyridinone；3-chloro-1-(2-methylpropyl)-4-(4-phenylpiperidin-1-yl)pyridin-2-one
• CAS: 1127498-55-8
• 化学式: C₂₀H₂₅ClN₂O
• 分子量: 344.884
• InChiKey: JDKWNHPOHQWVSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-isobutyl-4-(4-phenyl-1-piperidyl)pyridin-2-one 在 N-氯代丁二酰亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以83%的产率得到3-chloro-1-isobutyl-4-(4-phenyl-1-piperidyl)pyridin-2-one
  参考文献：
  名称：

  Discovery of 1-Butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-(1H)-pyridone (JNJ-40411813): A Novel Positive Allosteric Modulator of the Metabotropic Glutamate 2 Receptor

  摘要：

  We previously reported the discovery of 4-aryl-substituted pyridones with mGlu2 PAM activity starting from the HTS hit 5. In this article, we describe a different exploration from 5 that led to the discovery of a novel subseries of phenylpiperidine-substituted pyridones. The optimization strategy involved the introduction of different spacers between the pyridone core and the phenyl ring of 5. The fine tuning of metabolism and hERG followed by differentiation of advanced leads that were identified on the basis of PK profiles and in vivo potency converged on lead compound 36 (JNJ-40411813). Full in vitro and in vivo profiles indicate that 36 displayed an optimal interplay between potency, selectivity, favorable ADMET/PK and cardiovascular safety profile, and central EEG activity. Compound 36 has been investigated in the clinic for schizophrenia and anxious depression disorders.

  DOI：

  10.1021/jm500496m

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。
• 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。
• 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：US11369606B2

  公开（公告）日：2022-06-28

  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。