Comprehensively characterized fluorescent probes for the histamine H receptor (HR) and especially for the HR orthologs [e.g., human (h) and mouse (m)] are highly needed as versatile complementary tools to radioligands.
View Article and Find Full Text PDFDifferences in sequence homology between human (h), mouse (m), and rat (r) histamine H receptors (HR) cause discrepancies regarding affinities, potencies, and/or efficacies of ligands and therefore compromise translational animal models and the applicability of radioligands. Aiming at a radioligand enabling robust and comparative binding studies at the h/m/rHRs, 2,4-diaminopyrimidines were synthesized and pharmacologically investigated. The most notable compounds identified were two (partial) agonists with comparable potencies at the h/m/rHRs: UR-DEBa148 (-neopentyl-4-(1,4,6,7-tetrahydro-5-imidazo[4,5-]pyridin-5-yl)pyrimidin-2-amine bis(2,2,2-trifluoroacetate), ), the most potent [pEC (reporter gene assay) = 9.
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