Functionalized Congeners of 2H-Chromene P2Y₆ Receptor Antagonists.

ABSTRACT: The P2Y₆ receptor (P2Y₆R), a G_q-coupled receptor, is a potential drug discovery target for various inflammatory and degenerative conditions. Antagonists have been shown to attenuate colitis, acute lung injury, etc. In the search for competitive antagonists, we have investigated the SAR of 3-nitro-2-(trifluoromethyl)-2H-chromene derivatives, although high affinity is lacking. We now reveal that long-chain amino-functionalized congeners display greatly enhanced affinity in the antagonism of UDP-induced Ca²⁺ mobilization in human (h) P2Y₆R-transfected 1321N1 astrocytoma cells. A 6-(Boc-amino-n-heptylethynyl) analogue 30 (MRS4940) had an IC₅₀ of 162 nM, which was a 123-fold greater affinity than the c

SUBMITTER: Oliva P 

PROVIDER: S-EPMC11352859 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature