Activation of the Gi protein-coupled A3 adenosine receptor (AR) is associated with anticancer, antiischemic and anti-inflammatory effects. hA3 AR antagonists are being examined as promising agents for the treatment of glaucoma.1
Fluorescent probes are useful tools to investigate specific subcellular components in cells, tissues and organisms. In high throughput screening, fluorescent ligands represents a safer, more powerful and more versatile alternative to radioligands.2
We have recently reported a series of pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) based fluorophore-conjugated hA3 AR antagonists.3 Unfortunately, none of them reached affinities in the nM range. Here we report a novel series of PTP based fluorophore-conjugated hA3 AR antagonist with an additional pharmacophoric group at the 5-position, in order to obtain more potent hA3 AR antagonists.
References
1. Müller, C.E.; Jacobson, K.A. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim. Biophys. Acta 2011, 1808, 1290-1308.
2. Kuder,K.; Kiec-Kononowicz, K. Fluorescent GPCR ligands as new tools in pharmacology. Curr. Med. Chem. 2008, 15, 2132–2143.
3. Kozma, E.; Kumar, T.S.; Federico, S.; Phan, K.; Balasubramanian, R.; Gao, Z.G.; Paoletta, S.; Moro, S.; Spalluto, G.; Jacobson, K.A. Novel fluorescent antagonist as a molecular probe in A3 adenosine receptor binding assays using flow cytometry. Biochem. Pharmacol. 2012, 83, 1552-1561.
