Design and synthesis of potent 1,2,4-trisubstituted imidazolinone derivatives with dual p38αMAPK and ERK1/2 inhibitory activity

European Journal of Medicinal Chemistry
Fadi M AwadallahHanan H Georgey

Abstract

The synthesis of new 1,2,4-trisubstituted imidazolinone derivatives was described. The new compounds were designed as dual p38αMAPK and ERK1/2 inhibitors through hybridization of pharmacophoric elements associated with inhibition of these kinases. The kinase inhibition assay revealed excellent activity in the nanomolar range; especially compounds 6d and 7h which seemed promising candidates for such dual activity with IC50 values of 4.5 and 4.7 nM against p38αMAP, 25.0 and 24.0 nM against ERK1, and 3.2 and 3.5 nM against ERK2, respectively. These compounds were further tested for their antiproliferative activity against nine cancer cell lines, where they elicited high activity in the sub-micromolar range against breast, prostate and melanoma cells.

References

Nov 7, 2006·IUBMB Life·Zhimin Lu, Shuichan Xu
Mar 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lucy Gossage, Tim Eisen

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Citations

Mar 20, 2020·Future Medicinal Chemistry·Shelly Pathania, Ravindra K Rawal
Apr 24, 2020·Anti-cancer Agents in Medicinal Chemistry·Qing-Shan LiBan-Feng Ruan

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