1-benzyl-2-oxo-3-methyl-2,3-dihydro-1H-benzimidazole-5-carboxylic acid methyl ester | 1646359-33-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-benzyl-2-oxo-3-methyl-2,3-dihydro-1H-benzimidazole-5-carboxylic acid methyl ester
• CAS: 1646359-33-2
• 化学式: C₁₇H₁₆N₂O₃
• 分子量: 296.326
• InChiKey: WKZWFZVATDHQEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.17
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  53.23
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-benzyl-2-oxo-3-methyl-2,3-dihydro-1H-benzimidazole-5-carboxylic acid methyl ester 在 五氯化磷 、 三乙胺 、 丙酮氰醇 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 3.0h， 生成 1-benzyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one
  参考文献：
  名称：

  Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4-Hydroxyphenylpyruvate dioxygenase inhibitors

  摘要：

  4-Hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia. Inhibition of HPPD can effectively alleviate the symptoms of type I tyrosinemia. However, only one commercial HPPD inhibitor, 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione (NTBC), has been available for clinical use so far. In the present study, a series of novel pyrazole-benzimidazolone hybrids were designed, synthesized and evaluated as potent human HPPD inhibitors. Most of the new compounds displayed significant inhibitory activity against the recombinant human HPPD. Moreover, compound 91 was identified as the most potent candidate with IC50 value of 0.021 mu M against recombinant human HPPD, about 3-fold more potent than NTBC. Thus the pyrazole-benzimidazolone hybrid has great potential to be further developed for the treatment of type I tyrosinemia. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.018
• 作为产物：
  描述：

  4-氯-3-硝基苯甲酸甲酯 在 氢气 、 palladium(II) hydroxide 、 sodium hydride 作用下， 以 1,4-二氧六环 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 86.0h， 生成 1-benzyl-2-oxo-3-methyl-2,3-dihydro-1H-benzimidazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4-Hydroxyphenylpyruvate dioxygenase inhibitors

  摘要：

  4-Hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia. Inhibition of HPPD can effectively alleviate the symptoms of type I tyrosinemia. However, only one commercial HPPD inhibitor, 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione (NTBC), has been available for clinical use so far. In the present study, a series of novel pyrazole-benzimidazolone hybrids were designed, synthesized and evaluated as potent human HPPD inhibitors. Most of the new compounds displayed significant inhibitory activity against the recombinant human HPPD. Moreover, compound 91 was identified as the most potent candidate with IC50 value of 0.021 mu M against recombinant human HPPD, about 3-fold more potent than NTBC. Thus the pyrazole-benzimidazolone hybrid has great potential to be further developed for the treatment of type I tyrosinemia. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.018

文献信息

• [EN] GPR40 RECEPTOR AGONIST, METHODS OF PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE INGREDIENT<br/>[FR] AGONISTE DU RÉCEPTEUR GPR40, PROCÉDÉS DE PRÉPARATION DE CELUI-CI, ET COMPOSITIONS PHARMACEUTIQUES CONTENANT CELUI-CI EN TANT QUE SUBSTANCE ACTIVE
  申请人：LG LIFE SCIENCES LTD

  公开号：WO2014073904A1

  公开（公告）日：2014-05-15

  The present invention relates to a novel compound having GPR40 receptor agonist activity that promotes insulin secretion and inhibits blood sugar rise after glucose loading, and is thereby useful for the treatment of diabetes and complications thereof, the preparation method thereof and pharmaceutical composition containing them as an active ingredient.

  本发明涉及一种具有GPR40受体激动剂活性的新化合物，可促进胰岛素分泌并抑制葡萄糖负荷后血糖升高，因此适用于糖尿病及其并发症的治疗，以及包含它们作为活性成分的制备方法和药物组合物。