caa a22 4500 477127347 CHVBK 20180405111653.0 cr unu---uuuuu 170330e19970401xx s 000 0 eng 10.1023/A:1012172121453 doi (NATIONALLICENCE)springer-10.1023/A:1012172121453 Synthesis and β-Adrenergic Activities of R-Fluoronaphthyloxypropanolamine [Elektronische Daten] [Adeboye Adejare, Sophie Sciberras] Purpose. Many biogenic amines where an aromatic proton is substituted with fluorine have exhibited pharmacological properties that are dependent on the position of fluorine on the aromatic ring. For example, 6-fluoroepinephrine is selective for α-adrenergic receptors whereas the 2-fluoroisomer is selective for β-receptors. Aryloxypropanolamines are β-receptor agonists or antagonists, depending on the aryl group and its substituents. We therefore hypothesized that fluorine substitution on the aromatic ring could lead to significant biological effects in this class. A target with fluorine on naphthyl group of a known β-antagonist was chosen for investigation. Methods. Synthesis of the target compound began with fluoronaphthalene and involved introduction of 4-hydroxy group by Friedel-Crafts acylation followed by Baeyer Villiger oxidation. The side chain was introduced stereoselectively using the chiral synthon (2R)-glycidyl 3-nitrobenzenesulfonate, a Sharpless epoxidation technique. The epoxide was opened with t-butyl amine. HPLC methods were used to characterize %ee of the enantiomer. Results. The target compound was synthesized in several hundred milligram quantity, and in good yield and high enantiomeric excess, showing practicality of the synthetic scheme. It exhibited potent binding activities on β-adrenergic receptors, and was found to be two times selective for β2-receptors over β1. Conclusions. The current report demonstrates that aromatic fluorine substitution on β-adrenergic ligands can be achieved, and that such can be used to obtain binding selectivity between β receptors. Plenum Publishing Corporation, 1997 fluoroaromatic nationallicence naphthyloxypropanolamine nationallicence aryloxypropanolamine nationallicence enantioselective synthesis nationallicence β-adrenoceptor ligands nationallicence Adejare Adeboye Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 64110, Kansas City, Missouri aut Sciberras Sophie Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 64110, Kansas City, Missouri aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 533-536 0724-8741 14:4<533 1997 14 11095 https://doi.org/10.1023/A:1012172121453 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012172121453 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Adejare Adeboye Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 64110, Kansas City, Missouri aut NATIONALLICENCE 700 1- Sciberras Sophie Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 64110, Kansas City, Missouri aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 533-536 0724-8741 14:4<533 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer