@article { , title = {Synthesis and characterization of high-affinity 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human ?-adrenoceptors}, abstract = {The growing practice of exploiting noninvasive fluorescence-based techniques to study G protein-coupled receptor pharmacology at the single cell and single molecule level demands the availability of high-quality fluorescent ligands. To this end, this study evaluated a new series of red-emitting ligands for the human ?-adrenoceptor family. Upon the basis of the orthosteric ligands propranolol, alprenolol, and pindolol, the synthesized linker-modified congeners were coupled to the commercially available fluorophore BODIPY 630/650-X. This yielded high-affinity ?-adrenoceptor fluorescent ligands for both the propranolol and alprenolol derivatives; however, the pindolol-based products displayed lower affinity. A fluorescent diethylene glycol linked propranolol derivative (18a) had the highest affinity (log KD of ?9.53 and ?8.46 as an antagonist of functional ?2- and ?1-mediated responses, respectively). Imaging studies with this compound further confirmed that it can be employed to selectively label the human ?2-adrenoceptor in single living cells, with receptor-associated binding prevented by preincubation with the nonfluorescent ?2-selective antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118551)}, doi = {10.1021/jm2008562}, eissn = {1520-4804}, issn = {0022-2623}, issue = {19}, journal = {Journal of Medicinal Chemistry}, note = {Missed from ePrints no. 2734.}, pages = {6874-6887}, publicationstatus = {Published}, publisher = {American Chemical Society}, url = {https://nottingham-repository.worktribe.com/output/1304279}, volume = {54}, year = {2011}, author = {Baker, Jillian G. and Adams, Luke A. and Salchow, Karolina and Mistry, Shailesh N. and Middleton, Richard J. and Hill, Stephen J. and Kellam, Barrie} }