Synthesis and evaluation of highly selective quinazoline-2,4-dione ligands for sphingosine-1-phosphate receptor 2.

ABSTRACT: A series of twenty-nine new quinazoline-2,4-dione compounds were synthesized and their IC₅₀ values for binding toward sphingosine-1-phosphate receptor 2 (S1PR2) were determined using a [³²P]S1P binding assay. Seven compounds 2a, 2g, 2h, 2i, 2j, 2k, and 5h exhibit high S1PR2 binding potencies (IC₅₀ values < 50 nM) and four of these new compounds 2g, 2i, 2j, and 2k have IC₅₀ values (<10 nM) of 6.3, 5.7, 4.8, and 2.6 nM, and are highly selective for S1PR2 over other S1PR subtypes, S1PR1, 3, 4, and 5. Compounds 2a and 2i were chosen for C-11 radiosynthesis through O-[¹¹C]methylation of precursors 13 and 2k with good radiochemical yields (35-40%), high chemical and radiochemical purity (>98%), and high molar activity (153-222 GBq μmo

SUBMITTER: Luo Z 

PROVIDER: S-EPMC8864552 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature