195053-82-8Relevant academic research and scientific papers
UR-DEBa242: A Py-5-Labeled Fluorescent Multipurpose Probe for Investigations on the Histamine H3 and H4 Receptors
Bartole, Edith,Gr?tz, Lukas,Littmann, Timo,Wifling, David,Seibel, Ulla,Buschauer, Armin,Bernhardt, Günther
supporting information, p. 5297 - 5311 (2020/06/08)
Comprehensively characterized fluorescent probes for the histamine H3 receptor (H3R) and especially for the H4R orthologs [e.g., human (h) and mouse (m)] are highly needed as versatile complementary tools to radioligands. In view of fluorescent probes for BRET-based binding studies and for localizing the H4R in live cells, we synthesized and biologically characterized Py-5-labeled histamine derivatives. The most notable compound was UR-DEBa242 (26, 1-[4-(1H-Imidazol-4-yl)butyl]-4-{(1E,3E)-4-[4-(dimethylamino)phenyl]buta-1,3-dienyl}-2,6-dimethylpyridinium hydrotrifluoroacetate trifluoroacetate), acting as a partial agonist at the hH3R [pEC50 (reporter gene) 8.77] and as an inverse agonist/antagonist at the h/mH4Rs [pIC50 (reporter gene) 8.76/7.08; pIC50/pKb (β-arrestin2) 7.81/7.30]. In confocal microscopy, 26 proved suitable for hH4R localization and trafficking studies in live cells. BRET-based binding at the NLuc-hH3,4Rs/mH4R [pKd 8.78/7.75/7.18, comparable to binding constants from radioligand binding/flow cytometry; fast association/dissociation (a?2 min)] revealed 26 as a useful molecular tool to determine hH3,4Rs/mH4R binding affinities of ligands binding to these receptors.
Novel H3 receptor antagonists. Sulfonamide homologs of histamine.
Wolin,Connolly,Afonso,Hey,She,Rivelli,Willams,West Jr.
, p. 2157 - 2162 (2007/10/03)
Sulfonamides derived from 4(5)-(omega-aminoalkyl)-1H-imidazoles containing chain lengths of three- to five-carbons were synthesized. Good to moderate H3 receptor binding affinities were observed for several butyl and pentyl homologs, whereas binding affinities were considerably weaker in the propyl series. Separation of the imidazole ring and the sulfonamide unit by a four- or five-carbon tether afforded potent H3 receptor antagonists.
