کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1375408 | 981938 | 2008 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and in vitro antimycobacterial activity of B-ring modified diaryl ether InhA inhibitors Synthesis and in vitro antimycobacterial activity of B-ring modified diaryl ether InhA inhibitors](/preview/png/1375408.png)
Previous structure-based design studies resulted in the discovery of alkyl substituted diphenyl ether inhibitors of InhA, the enoyl reductase from Mycobacterium tuberculosis. Compounds such as 5-hexyl-2-phenoxyphenol 19 are nM inhibitors of InhA and inhibit the growth of both sensitive and isoniazid-resistant strains of Mycobacterium tuberculosis with MIC90 values of 1–2 μg/mL. However, despite their promising in vitro activity, these compounds have Clog P values of over 5. In efforts to reduce the lipophilicity of the compounds, and potentially enhance compound bioavailability, a series of B ring analogues of 19 were synthesized that contained either heterocylic nitrogen rings or phenyl rings having amino, nitro, amide, or piperazine functionalities. Compounds 3c, 3e, and 14a show comparable MIC90 values to that of 19, but have improved Clog P values.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 10, 15 May 2008, Pages 3029–3033