Synthesis and biological evaluation of carboxamide and quinoline derivatives as P2X7R antagonists.

ABSTRACT: P2X7 receptor (P2X7R) has a key role in different pathological conditions, importantly overexpressed and activated in cancers. We explored the structure activity relationship (SAR) of three novel pyrazines, quinoline-carboxamide and oxadiazole series. Their selective inhibitory potency in Ca²⁺ mobilization assay using h-P2X7R-MCF-7 cells improved with phenyl ring substitutions (-OCF₃, -CF₃, and -CH₃) in carboxamide and oxadiazole derivatives, respectively. However, highly electronegative fluoro, chloro, and iodo substitutions enhanced affinity. 1e, 2f, 2e, 1d, 2 g and 3e were most potent and selective toward h-P2X7R (IC₅₀ values 0.457, 0.566, 0.624, 0.682, 0.813 and 0.890 µM, respectively) and were inactive at h-P2X4R, h-P2X₂

SUBMITTER: Shah Q 

PROVIDER: S-EPMC10544280 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature