4-benzyloxy-1-[2-(4-{bromomethyl}-2-methyl-phenyl)-2-oxo-ethyl]-1H-pyridin-2-one | 1453499-98-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-benzyloxy-1-[2-(4-{bromomethyl}-2-methyl-phenyl)-2-oxo-ethyl]-1H-pyridin-2-one
• 英文别名: 4-benzyloxy-1-[2-(4-bromomethyl-2-methylphenyl)-2-oxoethyl]-1H-pyridin-2-one；4-Benzyloxy-1-[2-(4-bromomethyl-2-methyl-phenyl)-2-oxo-ethyl]-1H-pyridin-2-one；1-[2-[4-(bromomethyl)-2-methylphenyl]-2-oxoethyl]-4-phenylmethoxypyridin-2-one
• CAS: 1453499-98-3
• 化学式: C₂₂H₂₀BrNO₃
• 分子量: 426.31
• InChiKey: OGFCKSFOOJJQGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-benzyloxy-1-[2-(4-{bromomethyl}-2-methyl-phenyl)-2-oxo-ethyl]-1H-pyridin-2-one 、 3-羟基氮杂环丁烷盐酸盐 在 乙腈 、 水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 4-benzyloxy-1-{2-[4-(3-hydroxy-azetidin-1-ylmethyl)-2-methyl-phenyl]-2-oxo-ethyl}-1H-pyridin-2-one
  参考文献：
  名称：

  Pyridone and pyridazinone derivatives as anti-obesity agents

  摘要：

  吡啶酮和吡啶嗪衍生物具有抗黑素浓集激素（MCH）活性，并可用作抗肥胖药物。

  公开号：

  US08933079B2
• 作为产物：
  描述：

  4-苄氧基-2(1H)-吡啶酮 在 三溴化磷 、 caesium carbonate 作用下， 以 二氯甲烷 为溶剂， 生成 4-benzyloxy-1-[2-(4-{bromomethyl}-2-methyl-phenyl)-2-oxo-ethyl]-1H-pyridin-2-one
  参考文献：
  名称：

  Design, synthesis and evaluation of MCH receptor 1 antagonists—Part III: Discovery of pre-clinical development candidate BI 186908

  摘要：

  Although overweight and obesity are highly prevalent conditions, options to treat them are still very limited. As part of our search for safe and effective MCH-R1 antagonists for the treatment of obesity, two series of pyridones and pyridazinones were evaluated. Optimization was aimed at improving DMPK properties by increasing metabolic stability and improving the safety profile by reducing inhibition of the hERG channel and reducing the potential to induce phospholipidosis. Steric shielding of a labile keto moiety with an ortho-methyl group and fine-tuning of the polarity in several parts of the molecule resulted in BI 186908 (11g), a potent and selective MCH-R1 antagonist with favorable DMPK and CMC properties. Chronic administration of BI 186908 resulted in significant body weight reduction comparable to sibutramine in a 4 week diet-induced obesity model in rats. Based on its favorable safety profile, BI 186908 was advanced to pre-clinical development. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.065

文献信息

• NEW COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
  申请人：OOST Thorsten

  公开号：US20130237515A1

  公开（公告）日：2013-09-12

  The present invention relates to compounds of general formula I, wherein the groups R 1 , R 2 , L 1 , L 2 , U and B are as defined in the application, which have valuable pharmacological properties, and in particular modulate the activity of the MCH receptor.

  本发明涉及一般式I的化合物，其中基团R1、R2、L1、L2、U和B如申请中所定义，具有有价值的药理特性，特别是调节MCH受体的活性。
• [EN] PYRIDINONE AND PYRIDAZINONE DERIVATIVES AS MCH - RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS DE PYRIDINONE ET PYRIDAZINONE EN TANT QUE MODULATEURS DU RÉCEPTEUR DE MCH
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013131935A1

  公开（公告）日：2013-09-12

  The present invention relates to compounds of general formula I, wherein the groups R1, R2, L1, L2, U and B are as defined in the application, which have valuable pharmacological properties, and in particular modulate the activity of the MCH receptor.

  本发明涉及一般式I的化合物，其中R1、R2、L1、L2、U和B组分如申请中所定义，具有有价值的药理特性，特别是调节MCH受体活性。
• PYRIDINONE AND PYRIDAZINONE DERIVATIVES AS MCH-RECEPTOR MODULATORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2822937B1

  公开（公告）日：2016-12-21
• US8933079B2
  申请人：——

  公开号：US8933079B2

  公开（公告）日：2015-01-13
• Design, synthesis and evaluation of MCH receptor 1 antagonists—Part III: Discovery of pre-clinical development candidate BI 186908
  作者：Thorsten Oost、Armin Heckel、Jörg T. Kley、Thorsten Lehmann、Stephan Müller、Gerald J. Roth、Klaus Rudolf、Kirsten Arndt、Ralph Budzinski、Martin Lenter、Ralf R.H. Lotz、Gerd-Michael Maier、Michael Markert、Leo Thomas、Dirk Stenkamp

  DOI：10.1016/j.bmcl.2015.05.065

  日期：2015.8

  Although overweight and obesity are highly prevalent conditions, options to treat them are still very limited. As part of our search for safe and effective MCH-R1 antagonists for the treatment of obesity, two series of pyridones and pyridazinones were evaluated. Optimization was aimed at improving DMPK properties by increasing metabolic stability and improving the safety profile by reducing inhibition of the hERG channel and reducing the potential to induce phospholipidosis. Steric shielding of a labile keto moiety with an ortho-methyl group and fine-tuning of the polarity in several parts of the molecule resulted in BI 186908 (11g), a potent and selective MCH-R1 antagonist with favorable DMPK and CMC properties. Chronic administration of BI 186908 resulted in significant body weight reduction comparable to sibutramine in a 4 week diet-induced obesity model in rats. Based on its favorable safety profile, BI 186908 was advanced to pre-clinical development. (C) 2015 Elsevier Ltd. All rights reserved.