methyl 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)thiophene-2-carboxylic acid | 1314092-20-0

• 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 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)thiophene-2-carboxylic acid
• CAS: 1314092-20-0
• 化学式: C₁₄H₉N₃O₂S
• 分子量: 283.31
• InChiKey: HLFSUMAYFMNKKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  78.91
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)thiophene-2-carboxylic acid 、 环丙胺 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以90%的产率得到N-cyclopropyl-5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)thiophene-2-carboxamide
  参考文献：
  名称：

  Optimization of Potent Inhibitors of P. falciparum Dihydroorotate Dehydrogenase for the Treatment of Malaria

  摘要：

  Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. We report herein the synthesis and structure-activity relationship of a series of 5-(2-methylbenzimidazol-1-yl)-N-alkylthiophene-2-carboxamides that are potent inhibitors against PfDHODH but do not inhibit the human enzyme. On the basis of efficacy observed in three mouse models of malaria, acceptable safety pharmacology risk assessment and safety toxicology profile in rodents, lack of potential drug-drug interactions, acceptable ADME/pharmacokinetic profile, and projected human dose, 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)-N-cyclopropylthiophene-2-carboxamide 2q was identified as a potential drug development candidate.

  DOI：

  10.1021/ml200143c
• 作为产物：
  描述：

  5-硝基噻吩-2-羰酰氯 在 盐酸 、 20 % Pd(OH)2/C 、 水 、 氢气 、 N,N,N-三乙基-1-丁烷铵氯化物 、 tin(ll) chloride 、 potassium hydroxide 、 lithium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 methyl 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)thiophene-2-carboxylic acid
  参考文献：
  名称：

  Optimization of Potent Inhibitors of P. falciparum Dihydroorotate Dehydrogenase for the Treatment of Malaria

  摘要：

  Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. We report herein the synthesis and structure-activity relationship of a series of 5-(2-methylbenzimidazol-1-yl)-N-alkylthiophene-2-carboxamides that are potent inhibitors against PfDHODH but do not inhibit the human enzyme. On the basis of efficacy observed in three mouse models of malaria, acceptable safety pharmacology risk assessment and safety toxicology profile in rodents, lack of potential drug-drug interactions, acceptable ADME/pharmacokinetic profile, and projected human dose, 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)-N-cyclopropylthiophene-2-carboxamide 2q was identified as a potential drug development candidate.

  DOI：

  10.1021/ml200143c