Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Bl. 9, Acad. G. Bonchev Str., Sofia 1113, Bulgaria.
Eur J Med Chem. 2012 Feb;48:45-56. doi: 10.1016/j.ejmech.2011.11.035. Epub 2011 Nov 28.
The synthesis of 47 structurally diverse compounds incorporating the (R)-2-amino-1-butanol motif has been realized. Ten of these compounds were found to exhibit in vitro specific activity against Mycobacterium tuberculosis H37Rv in a MIC range of 0.65 μM-14.03 μM. Five of the most active compounds 11, 22, 23, 31 and 42 (5.7-11.1 fold more active than ethambutol) can be outlined with very low cytotoxicity towards human embryonal kidney non-tumour cells (SI ranging from 91.2 to 375.4). For the purpose of comparison the (S)-enantiomers of these most active compounds have been synthesized and evaluated towards M. tuberculosis H(37)Rv showing no activity even at 20-32 fold higher concentrations.
已经实现了 47 种结构多样的化合物的合成，这些化合物中包含（R）-2-氨基-1-丁醇结构基。其中 10 种化合物在 MIC 范围为 0.65 μM-14.03 μM 时，对结核分枝杆菌 H37Rv 表现出体外特异性活性。最具活性的五种化合物 11、22、23、31 和 42（比乙胺丁醇活性高 5.7-11.1 倍）对人胚肾非肿瘤细胞的细胞毒性非常低（SI 范围为 91.2 至 375.4）。为了进行比较，还合成了这些最具活性化合物的（S）对映体，并对结核分枝杆菌 H（37）Rv 进行了评估，即使在浓度高 20-32 倍的情况下，也没有表现出活性。
