Department of Chemistry, Saurashtra University, Rajkot-360005, Gujarat, India.
Chem Biol Drug Des. 2011 Nov;78(5):881-6. doi: 10.1111/j.1747-0285.2011.01233.x. Epub 2011 Sep 21.
Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant antitubercular activity. In this study, we have synthesized new derivatives of 1,4-dihydropyridines bearing carbmethoxy and carbethoxy group at C-3 and C-5 of the 1,4-dihydropyridine ring. In addition, 1H-pyrazole ring is substituted at C-4 position. These analogues were synthesized by multi-component Hantzsch reaction. The in vitro antitubercular activity of compounds against Mycobacterium tuberculosis H(37) Rv was evaluated. The lowest minimum inhibitory concentration value, 0.02 μg/mL and SI > 500, was found for dimethyl 1,4-dihydro-4-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethylpyridine-3,5-dicarboxylate 3f, diethyl 1,4-dihydro-4-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethylpyridine-3,5-dicarboxylate 4c and diethyl 1,4-dihydro-4-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethyl pyridine-3,5-dicarboxylate 4e, making them more potent than first-line antitubercular drug isoniazid. In addition, these compounds exhibited relatively low cytotoxicity.
最近的研究表明，具有亲脂基团的 1,4-二氢吡啶-3,5-二羧酸衍生物具有显著的抗结核活性。在这项研究中，我们合成了新的 1,4-二氢吡啶衍生物，这些衍生物在 1,4-二氢吡啶环的 C-3 和 C-5 位带有羰甲氧基和羰乙氧基，此外，1H-吡唑环取代在 C-4 位置。这些类似物是通过多组分 Hantzsch 反应合成的。评估了化合物对结核分枝杆菌 H(37)Rv 的体外抗结核活性。化合物的最低最小抑菌浓度值为 0.02 μg/mL，SI>500，其中二甲基 1,4-二氢-4-(3-(4-硝基苯基)-1-苯基-1H-吡唑-4-基)-2,6-二甲基吡啶-3,5-二羧酸酯 3f、二乙基 1,4-二氢-4-(3-(4-氟苯基)-1-苯基-1H-吡唑-4-基)-2,6-二甲基吡啶-3,5-二羧酸酯 4c 和二乙基 1,4-二氢-4-(3-(4-溴苯基)-1-苯基-1H-吡唑-4-基)-2,6-二甲基吡啶-3,5-二羧酸酯 4e 的抑菌浓度最低，这使得它们比一线抗结核药物异烟肼更有效。此外，这些化合物表现出相对较低的细胞毒性。
