Ali, Eslam M. H.; El-Telbany, Rania Farag A.; Abdel-Maksoud, Mohammed S.; Ammar, Usama M.; Mersal, Karim I.; Zaraei, Seyed-Omar; El-Gamal, Mohammed I.; Choi, Se-In; Lee, Kyung-Tae; Kim, Hee-Kwon; Lee, Kwan Hyi; Oh, Chang-Hyun published the artcile< Design, synthesis, biological evaluation, and docking studies of novel (imidazol-5-yl)pyrimidine-based derivatives as dual BRAFV600E/p38α inhibitors>, Quality Control of 85740-98-3, the main research area is imidazolyl pyrimidine preparation BRAFV600E p38alpha inhibitor antitumor mol docking; BRAF(V600E); Imidazol-5-ylpyrimidine; MAPK14; Melanoma; Molecular docking; TNF-α.
In the present work, a new series of (imidazol-5-yl)pyrimidine I ( Ar = C6H5, 4-ClC6H4, 4-BrC6H4 etc.; X = F, Cl; R = OCH3, OH) was designed and synthesized as dual inhibitors of BRAFV600E and p38α kinases which are considered as key regulators in mitogen-activated protein kinase signalling pathway. The target compounds were evaluated for dual kinase inhibitory activity. The tested compounds exhibited nanomolar scale IC50 values against BRAFV600E and low to sub-micromolar IC50 range against p38α. Compound I (Ar = 4-OHC6H4; X = F; R = OH) was identified as the most potent dual BRAFV600E/p38α inhibitor with IC50 values of 2.49 and 85 nM, resp. Further deep investigation revealed that Compound I (Ar = 4-OHC6H5; X = F; R = OH) possesses inhibitory activity of TNF-α production in lipopolysaccharide-induced RAW 264.7 macrophages with IC50 value of 96.3 nM. Addnl., the target compounds efficiently frustrated the proliferation of LOX-IMVI melanoma cell line. Compound I (Ar = 4-OHC6H5; X = F; R = OH) showed a satisfactory antiproliferative activity with IC50 value of 13μM, while, compound I (Ar = 3-FC6H4; X = F; R = OCH3) exhibited the highest cytotoxicity potency with IC50 value of 0.9μM. Compound I (Ar = 3-FC6H4; X = F; R = OCH3) is 11.11-fold more selective toward LOX-IMVI melanoma cells than IOSE-80PC normal cells.
European Journal of Medicinal Chemistry published new progress about Antitumor agents. 85740-98-3 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Quality Control of 85740-98-3.
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