(R)-ethyl 2-(3-(1-hydroxy-3-phenylpropan-2-yl)ureido)-4-methylthiazole-5-carboxylate | 1072806-36-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-ethyl 2-(3-(1-hydroxy-3-phenylpropan-2-yl)ureido)-4-methylthiazole-5-carboxylate
• 英文别名: ethyl 2-[[(2R)-1-hydroxy-3-phenylpropan-2-yl]carbamoylamino]-4-methyl-1,3-thiazole-5-carboxylate
• CAS: 1072806-36-0
• 化学式: C₁₇H₂₁N₃O₄S
• 分子量: 363.437
• InChiKey: DUWFRCSFGGUOJI-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-ethyl 2-(3-(1-hydroxy-3-phenylpropan-2-yl)ureido)-4-methylthiazole-5-carboxylate 在 potassium carbonate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (R)-2-(4-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-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
• 作为产物：
  描述：

  2-氨基-4-甲基噻唑-5-甲酸乙酯 、 D-苯丙氨醇 、 N,N'-羰基二咪唑 在 乙酸乙酯 、 水 、 Brine 、 Sodium sulfate-III 作用下， 以 四氢呋喃 为溶剂， 反应 67.0h， 以to afford the title compound in 88% (3.20 g)的产率得到(R)-ethyl 2-(3-(1-hydroxy-3-phenylpropan-2-yl)ureido)-4-methylthiazole-5-carboxylate
  参考文献：
  名称：

  ORGANIC COMPOUNDS

  摘要：

  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。

  公开号：

  US20100233116A1

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。
• WO2008/127349
  申请人：——

  公开号：——

  公开（公告）日：——
• Systematic evaluation of amide bioisosteres leading to the discovery of novel and potent thiazolylimidazolidinone inhibitors of SCD1 for the treatment of metabolic diseases
  作者：Shaoyi Sun、Zaihui Zhang、Vishnumurthy Kodumuru、Natalia Pokrovskaia、Julia Fonarev、Qi Jia、Po-Yee Leung、Jennifer Tran、Leslie G. Ratkay、David G. McLaren、Chris Radomski、Sultan Chowdhury、Jianmin Fu、Brian Hubbard、Michael D. Winther、Natalie A. Dales

  DOI：10.1016/j.bmcl.2013.12.036

  日期：2014.1

  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.