methyl 2-oxo-1-propyl-2,3-dihydro-1H-benzimidazole-5-carboxylate | 762295-45-4

• 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: methyl 2-oxo-1-propyl-2,3-dihydro-1H-benzimidazole-5-carboxylate
• 英文别名: methyl 2-oxo-1-propyl-3H-benzimidazole-5-carboxylate
• CAS: 762295-45-4
• 化学式: C₁₂H₁₄N₂O₃
• 分子量: 234.255
• InChiKey: CUWTZYCWDFVHMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-oxo-1-propyl-2,3-dihydro-1H-benzimidazole-5-carboxylate 在 五氯化磷 、 sodium hydride 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 52.0h， 生成 1,3-dimethyl-1H-pyrazol-5-yl 2-oxo-1,3-dipropyl-2,3-dihydro-1H-benzo[d]imidazole-5-carboxylate
  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：

  methyl 3-nitro-N⁴-propylaminobenzoate 在 氢气 、 palladium(II) hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 29.0h， 生成 methyl 2-oxo-1-propyl-2,3-dihydro-1H-benzimidazole-5-carboxylate
  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

• WO2007/69053
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] BENZIMIDAZOLE ANTAGONISTS OF THE H-3 RECEPTOR<br/>[FR] ANTAGONISTES BENZIMIDAZOLIQUES DU RÉCEPTEUR H-3
  申请人：PFIZER PROD INC

  公开号：WO2007069053A1

  公开（公告）日：2007-06-21

  [EN] This invention is directed to a compound of formula (I), as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula (I), a process of preparation of a compound of formula (I), a method of treatment of a disorder or condition that may be treated by antagonizing histamine H3 receptors, the method comprising administering to a mammal in need of such treatment a compound of formula (I) as described above, and a method of treatment of a disorder or condition selected from the group consisting of depression, mood disorders, schizophrenia, anxiety disorders, Alzheimer's disease, attention-deficit hyperactivity disorder (ADHD), attention-deficit disorder (ADD), psychotic disorders, cognitive disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy-induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the G1 tract, hyper and hypo motility and acidic secretion of the gastro-intestinal tract, the method comprising administering to a mammal in need of such treatment a compound of formula (I) as described above.
  [FR] La présente invention concerne un composé de formule (I) telle que définie ici, ou un de ses sels pharmaceutiquement acceptables ; une composition pharmaceutique contenant un composé de formule (I), un procédé de préparation d'un composé de formule (I), un procédé de traitement d'un trouble ou d'une maladie qui peut être traité en antagonisant les récepteurs histaminiques H3, le procédé comprenant l'administration à un mammifère nécessitant un tel traitement d'un composé de formule (I) tel que décrit ci-dessus, et un procédé de traitement d'un trouble ou d'une maladie choisi dans le groupe comprenant la dépression, les troubles de l'humeur, la schizophrénie, les troubles de l'anxiété, la maladie d'Alzheimer, le trouble d'hyperactivité avec déficit de l'attention (THADA), le trouble de déficit de l'attention (TDA), les troubles psychotiques, les troubles cognitifs, les troubles du sommeil, l'obésité, le vertige, l'épilepsie, le mal des transports, les maladies respiratoires, l'allergie, les réactions d'origine allergique des voies respiratoires, la rhinite allergique, la congestion nasale, la congestion allergique, la congestion, l'hypotension, les maladies cardiovasculaires, les maladies du système gastro-intestinal, l'hypermotilité et l'hypomotilité et la sécrétion acide dans le système gastro-intestinal, le procédé comprenant l'administration à un mammifère nécessitant un tel traitement d'un composé de formule (I) tel que décrit ci-dessus.
• Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4-Hydroxyphenylpyruvate dioxygenase inhibitors
  作者：Yu-Ling Xu、Hong-Yan Lin、Xu Ruan、Sheng-Gang Yang、Ge-Fei Hao、Wen-Chao Yang、Guang-Fu Yang

  DOI：10.1016/j.ejmech.2015.01.018

  日期：2015.3

  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.