Organic Chemistry Division-II, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
Bioorg Med Chem. 2011 Aug 15;19(16):4772-81. doi: 10.1016/j.bmc.2011.06.085. Epub 2011 Jul 2.
A series of novel 2-butyl-4-chloro-1-methylimidazole embedded aryl and heteroaryl derived chalcones and pyrazoles were synthesized and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. The condensation of 2-butyl-4-chloro-1-methylimidazole-5-carboxaldehyde with various aryl and heteroaryl methyl ketones in the presence of 10% aqueous NaOH in methanol proceeded efficiently to give the respective chalcones in very good yields. Further, the reaction of chalcones with hydrazine hydrate in acetic acid gave substituted pyrazole analogues. Screening all 36 new compounds using ACE inhibition assay, resulted chalcones with better ACE inhibitory activity compared to the respective pyrazole analogues. Among the chalcones 4a-r, three compounds, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(5-chlorothiophen-2-yl)prop-2-enone 4i, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(1H-pyrrol-2-yl)prop-2-enone 4l, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(dibenzo[b,d] thiophen-2-yl)prop-2-enone 4q were resulted as most active ACE inhibitors with IC(50) of 3.60 μM, 2.24 μM, and 2.68 μM, respectively.
一系列新型 2-丁基-4-氯-1-甲基咪唑嵌入芳基和杂芳基衍生的查尔酮和吡唑被合成，并评估其血管紧张素转换酶（ACE）抑制活性。在甲醇中的 10％水性 NaOH 存在下，将 2-丁基-4-氯-1-甲基咪唑-5-甲醛与各种芳基和杂芳基甲基酮缩合，以非常好的产率得到相应的查尔酮。此外，查尔酮与水合肼在乙酸中的反应得到取代的吡唑类似物。使用 ACE 抑制测定法筛选所有 36 种新化合物，结果查尔酮比相应的吡唑类似物具有更好的 ACE 抑制活性。在查尔酮 4a-r 中，三种化合物，（E）-3-（2-丁基-4-氯-1-甲基-1H-咪唑-5-基）-1-（5-氯噻吩-2-基）丙烯-2-酮 4i、（E）-3-（2-丁基-4-氯-1-甲基-1H-咪唑-5-基）-1-（1H-吡咯-2-基）丙烯-2-酮 4l、（E）-3-（2-丁基-4-氯-1-甲基-1H-咪唑-5-基）-1-（二苯并[b，d]噻吩-2-基）丙烯-2-酮 4q 被证明是最有效的 ACE 抑制剂，其 IC50 分别为 3.60 μM、2.24 μM 和 2.68 μM。
