Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, Lucknow 226 001, India.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5589-93. doi: 10.1016/j.bmcl.2011.06.076. Epub 2011 Jul 2.
In search of potential therapeutics for tuberculosis, we describe herein synthesis and biological evaluation of some substituted 4-arylthiazol-2-amino derivatives as modified analogues of the antiprotozoal drug Nitazoxanide (NTZ), which has recently been reported as potent inhibitor of Mtb H(37)Rv (Mtb MIC=52.12 μM) with an excellent ability to evade resistance. Among the synthesized derivatives, the two compounds 7a (MIC=15.28 μM) and 7c (MIC=17.03 μM) have exhibited about three times better Mtb growth inhibitory activity over NTZ and are free from any cytotoxicity (Vero CC(50) of 244 and 300 μM respectively). These two compounds represent promising leads for further optimization.
在寻找结核病潜在治疗药物的过程中，我们描述了一些取代的 4-芳基噻唑-2-氨基衍生物的合成和生物评价，这些衍生物是抗原生动物药物硝唑尼特（NTZ）的修饰类似物，最近有报道称其是结核分枝杆菌 H（37）Rv 的有效抑制剂（结核分枝杆菌 MIC=52.12 μM），并且具有很好的抗耐药能力。在所合成的衍生物中，化合物 7a（MIC=15.28 μM）和 7c（MIC=17.03 μM）对结核分枝杆菌的生长抑制活性比 NTZ 好约三倍，且没有任何细胞毒性（分别为 244 和 300 μM 的 Vero CC（50））。这两种化合物是进一步优化的有前途的先导化合物。
