کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1377355 | 981976 | 2008 | 4 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and anti-HIV activity of GS-9148 (2′-Fd4AP), a novel nucleoside phosphonate HIV reverse transcriptase inhibitor Synthesis and anti-HIV activity of GS-9148 (2′-Fd4AP), a novel nucleoside phosphonate HIV reverse transcriptase inhibitor](/preview/png/1377355.png)
GS-9148 (2′-Fd4AP, 4) has been identified as a nucleoside phosphonate reverse transcriptase (RT) inhibitor with activity against wild-type HIV (EC50 = 12 μM). Unlike many clinical RT inhibitors, relevant reverse transcriptase mutants (M184V, K65R, 6-TAMs) maintain a susceptibility to 2′-Fd4AP that is similar to wild-type virus. The 2′-fluorine group was rationally designed into the molecule to improve the selectivity profile and in preliminary studies using HepG2 cells, compound 4 showed no measurable effect on mitochondrial DNA content indicating a low potential for mitochondrial toxicity.
Compound 4 (2′-Fd4AP) was synthesized and maintained the favorable anti-HIV properties of 2 while demonstrating a marked reduction in mitochondrial toxicity to HepG2 cells.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 3, 1 February 2008, Pages 1120–1123