N-benzyl-4-methyl-2-(1H-pyrazol-4-yl)-1,3-thiazole-5-carboxamide | 1537889-53-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-benzyl-4-methyl-2-(1H-pyrazol-4-yl)-1,3-thiazole-5-carboxamide
• CAS: 1537889-53-4
• 化学式: C₁₅H₁₄N₄OS
• 分子量: 298.368
• InChiKey: QXIKCFKRTJCRAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  98.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-benzyl-4-methyl-2-(1H-pyrazol-4-yl)-1,3-thiazole-5-carboxamide 、 溴甲苯 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 生成 N-benzyl-2-(1-benzylpyrazol-4-yl)-4-methyl-1,3-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-溴-4-甲基噻唑-5-羧酸 在 四(三苯基膦)钯 、 potassium carbonate 、 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 、 甲苯 为溶剂， 生成 N-benzyl-4-methyl-2-(1H-pyrazol-4-yl)-1,3-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

文献信息

• 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.