4-methyl-2-(2-oxo-3-((tetrahydro-2H-pyran-2-yl)methyl)imidazolidin-1-yl)thiazole-5-carboxylic acid | 1072802-58-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-methyl-2-(2-oxo-3-((tetrahydro-2H-pyran-2-yl)methyl)imidazolidin-1-yl)thiazole-5-carboxylic acid
• 英文别名: 4-methyl-2-[3-(oxan-2-ylmethyl)-2-oxoimidazolidin-1-yl]-1,3-thiazole-5-carboxylic acid
• CAS: 1072802-58-4
• 化学式: C₁₄H₁₉N₃O₄S
• 分子量: 325.389
• InChiKey: WGPQIASMPPHEEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-氨甲基吡啶 、 4-methyl-2-(2-oxo-3-((tetrahydro-2H-pyran-2-yl)methyl)imidazolidin-1-yl)thiazole-5-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-methyl-2-(2-oxo-3-((tetrahydro-2H-pyran-2-yl)methyl)imidazolidin-1-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide
  参考文献：
  名称：

  Systematic evaluation of amide bioisosteres leading to the discovery of novel and potent thiazolylimidazolidinone inhibitors of SCD1 for the treatment of metabolic diseases

  摘要：

  Several five- and six-membered heterocycles were introduced to replace the C2-position amide bond of the original 2-aminothiazole-based hit compound 5. Specifically, replacement of the amide bond with an imidazolidinone moiety yielded a novel and potent thiazolylimidazolidinone series of SCD1 inhibitors. XEN723 (compound 22) was identified after optimization of the thiazolylimidazolidinone series. This compound demonstrated a 560-fold improvement in in vitro potency and reduced plasma desaturation indices in a dose dependent manner, with an EC50 of 4.5 mg/kg. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.036
• 作为产物：
  描述：

  2-氨基-4-甲基噻唑-5-甲酸乙酯 在 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 生成 4-methyl-2-(2-oxo-3-((tetrahydro-2H-pyran-2-yl)methyl)imidazolidin-1-yl)thiazole-5-carboxylic acid
  参考文献：
  名称：

  Systematic evaluation of amide bioisosteres leading to the discovery of novel and potent thiazolylimidazolidinone inhibitors of SCD1 for the treatment of metabolic diseases

  摘要：

  Several five- and six-membered heterocycles were introduced to replace the C2-position amide bond of the original 2-aminothiazole-based hit compound 5. Specifically, replacement of the amide bond with an imidazolidinone moiety yielded a novel and potent thiazolylimidazolidinone series of SCD1 inhibitors. XEN723 (compound 22) was identified after optimization of the thiazolylimidazolidinone series. This compound demonstrated a 560-fold improvement in in vitro potency and reduced plasma desaturation indices in a dose dependent manner, with an EC50 of 4.5 mg/kg. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.036

文献信息

• Heterocyclic compounds suitable for the treatment of diseases related to elevated lipid levels
  申请人：Novartis AG

  公开号：US08063084B2

  公开（公告）日：2011-11-22

  The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

  本发明提供了杂环衍生物，可以调节硬脂酰辅酶A去饱和酶的活性。还涵盖了使用这种衍生物来调节硬脂酰辅酶A去饱和酶的活性的方法，以及包含这种衍生物的制药组合物。
• ORGANIC COMPOUNDS
  申请人：Dales Natalie

  公开号：US20100233116A1

  公开（公告）日：2010-09-16

  The present invention provides heterocyclic derivatives hat modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

  本发明提供了能够调节硬脂酰辅酶A脱饱和酶活性的杂环衍生物。本发明还涵盖了使用这种衍生物来调节硬脂酰辅酶A脱饱和酶活性的方法，以及包含这种衍生物的药物组合物。
• Organic compounds
  申请人：Novartis AG

  公开号：US08293768B2

  公开（公告）日：2012-10-23

  The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

  本发明提供了可以调节硬脂酰辅酶A脱饱和酶活性的杂环衍生物。还涵盖了使用这些衍生物来调节硬脂酰辅酶A脱饱和酶活性的方法，以及包含这些衍生物的药物组合物。
• HETEROCYCLIC COMPOUNDS SUITABLE FOR THE TREATMENT OF DISEASES RELATED TO ELEVATED LIPID LEVEL
  申请人：Novartis AG

  公开号：EP2054408A2

  公开（公告）日：2009-05-06
• Heterocyclic compounds suitable for the treatment of diseases related to elevated lipid level
  申请人：Novartis AG

  公开号：EP2054408B1

  公开（公告）日：2016-07-13