Structure activity relationship of 3-nitro-2-(trifluoromethyl)-2H-chromene derivatives as P2Y₆ receptor antagonists.

ABSTRACT: Various 6-alkynyl analogues of a known 3-nitro-2-(trifluoromethyl)-2H-chromene antagonist 3 of the G_q-coupled P2Y₆ receptor (P2Y₆R) were synthesized using a Sonogashira reaction to replace a 6-iodo group. The analogues were tested in a functional assay consisting of inhibition of calcium mobilization in P2Y₆R-expressing astrocytoma cells elicited by native P2Y₆R agonist UDP. 6-Ethynyl and 6-cyano groups were installed, and the alkynes were extended through both alkyl and aryl spacers. The most potent antagonists, with IC₅₀ of ~1 µM, were found to be trialkylsilyl-ethynyl 7 and 8 (3-5 fold greater affinity than reference 3), t-butyl prop-2-yn-1-ylcarbamate 14 and p-carboxyphenyl-ethynyl 16 derivatives, and 3 and 8 displayed s

SUBMITTER: Jung YH 

PROVIDER: S-EPMC8240625 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature