Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, India.
Bioorg Med Chem Lett. 2011 Jul 1;21(13):3881-4. doi: 10.1016/j.bmcl.2011.05.032. Epub 2011 May 15.
A series of 35 2e,3e,6e-triaryltetrahydro-4(1H)-pyridinones, 2e,3e,5e,6e-tetraaryltetrahydro-4(1H)-pyridinones and their N-nitroso and N-cyano analogs have been prepared. All these 35 compounds obtained were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Among them, the N-nitrosopyridinones are found to be more active against MTB than the corresponding N-CN analogs, which, in turn, were slightly more active than NH analogs. In particular, the N-nitroso compounds, 3d, 4b and 4e with halogen-bearing phenyl rings at 2,6-positions showed maximum activity with MIC values of 3.97, 3.11 and 3.11 μM, being more efficacious than the first line anti-TB drugs, ciprofloxacin, ethambutol and pyrazinamide. A general trend has also been discerned in all the three classes of NH, N-CN and N-NO compounds, in each of which those bearing four aryl rings display higher activity than that having three analogously substituted aryl rings disclosing that lipophilicity could be an important factor underlying antimycobacterial activity.
已经制备了一系列 35 种 2e,3e,6e-三芳基四氢-4(1H)-吡啶酮、2e,3e,5e,6e-四芳基四氢-4(1H)-吡啶酮及其 N-亚硝基和 N-氰基类似物。对所有获得的 35 种化合物进行了体外抗结核分枝杆菌 H37Rv (MTB)活性筛选。其中，N-亚硝基吡啶酮对 MTB 的活性高于相应的 N-CN 类似物，而 N-CN 类似物又略高于 NH 类似物。特别是 2,6-位带有卤代芳基环的 N-亚硝基化合物 3d、4b 和 4e 表现出最大的活性，MIC 值分别为 3.97、3.11 和 3.11 μM，比一线抗结核药物环丙沙星、乙胺丁醇和吡嗪酰胺更有效。在 NH、N-CN 和 N-NO 这三类化合物中都发现了一种普遍的趋势，其中那些带有四个芳基环的化合物比带有三个类似取代芳基环的化合物具有更高的活性，这表明亲脂性可能是抗分枝杆菌活性的一个重要因素。
