4-(2-butyl-4-chloro-1H-imidazol-5-yl)-6-methyl-2-oxo-N-(m-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide

• 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: 4-(2-butyl-4-chloro-1H-imidazol-5-yl)-6-methyl-2-oxo-N-(m-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide
• 英文别名: 4-(2-butyl-4-chloro-1H-imidazol-5-yl)-6-methyl-N-(3-methylphenyl)-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide
• 化学式: C₂₀H₂₄ClN₅O₂
• 分子量: 401.896
• InChiKey: QBQLBPWJWMEFDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  98.9
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氧代-N-邻甲苯丁胺 、 咪唑醛 、 尿素 在 盐酸 作用下， 以 乙醇 为溶剂， 以75%的产率得到4-(2-butyl-4-chloro-1H-imidazol-5-yl)-6-methyl-2-oxo-N-(m-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide
  参考文献：
  名称：

  Preparation, biological evaluation and molecular docking study of imidazolyl dihydropyrimidines as potential Mycobacterium tuberculosis dihydrofolate reductase inhibitors

  摘要：

  A series of novel dihydropyrimidine derivatives bearing an imidazole nucleus at C-4 position were synthesized in excellent yields via Biginelli multi-component reaction. The newly synthesized compounds were characterized by IR, H-1 NMR, C-13 NMR and Mass spectroscopy. In vitro antitubercular evaluation of all the newly synthesized compounds 4a-p against Mycobacterium tuberculosis (Mtb) H(37)Rv showed, 4j (MIC: 0.39 mu g/mL; SI: >25.64), 4m (MIC: 0.78 mu g/mL; SI: >12.82) and 4p (MIC: 0.39 mu g/mL; SI: 24.10) as the most promising lead analogues. Compounds 4j, 4m and 4p displayed effective reduction in residual Mtb growth within the tuberculosis-infected macrophage model. Further, molecular docking study of active molecules 4j, 4m and 4p against Mycobacterium tuberculosis dihydrofolate reductase (Mtb DHFR) proved their potency as Mtb DHFR inhibitors acting as potential leads for further development. Pharmacokinetic properties leading to drug-likeness were also predicted for most active molecules 4j, 4m and 4p. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.06.082

文献信息

• Preparation, biological evaluation and molecular docking study of imidazolyl dihydropyrimidines as potential Mycobacterium tuberculosis dihydrofolate reductase inhibitors
  作者：N.C. Desai、A.R. Trivedi、Vijay M. Khedkar

  DOI：10.1016/j.bmcl.2016.06.082

  日期：2016.8

  A series of novel dihydropyrimidine derivatives bearing an imidazole nucleus at C-4 position were synthesized in excellent yields via Biginelli multi-component reaction. The newly synthesized compounds were characterized by IR, H-1 NMR, C-13 NMR and Mass spectroscopy. In vitro antitubercular evaluation of all the newly synthesized compounds 4a-p against Mycobacterium tuberculosis (Mtb) H(37)Rv showed, 4j (MIC: 0.39 mu g/mL; SI: >25.64), 4m (MIC: 0.78 mu g/mL; SI: >12.82) and 4p (MIC: 0.39 mu g/mL; SI: 24.10) as the most promising lead analogues. Compounds 4j, 4m and 4p displayed effective reduction in residual Mtb growth within the tuberculosis-infected macrophage model. Further, molecular docking study of active molecules 4j, 4m and 4p against Mycobacterium tuberculosis dihydrofolate reductase (Mtb DHFR) proved their potency as Mtb DHFR inhibitors acting as potential leads for further development. Pharmacokinetic properties leading to drug-likeness were also predicted for most active molecules 4j, 4m and 4p. (C) 2016 Elsevier Ltd. All rights reserved.