کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372018 | 981863 | 2009 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: New Ras CAAX mimetics: Design, synthesis, antiproliferative activity, and RAS prenylation inhibition New Ras CAAX mimetics: Design, synthesis, antiproliferative activity, and RAS prenylation inhibition](/preview/png/1372018.png)
Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing cysteine (C) by 2-hydroxymethylbenzodioxane or 2-aminomethylbenzodioxane, respectively etherified and amidified with 2′-methyl or 2′-methoxy substituted 2-carboxy-4-hydroxybiphenyl and 2,4-dicarboxybiphenyl. These pluri-substituted biphenyl systems, used as internal spacer and AA dipeptide bioisoster, were linked to the methyl ester of l-methionine, glycine or l-leucine by an amide bond. The resultant twelve pairs of stereoisomers at the dioxane C-2 were tested for antiproliferative effect finding the maximum activity for derivatives with methyleneoxy linker between benzodioxane and 2′-methylbiphenyl. Of these compounds, the one with terminal methionine and S configuration proved a good Ras prenylation inhibitor in a cell-based assay.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 18, 15 September 2009, Pages 5500–5504