PMID: 7932549Sep 30, 1994Paper

Synthesis, binding properties, and 18F labeling of fluorocarazolol, a high-affinity beta-adrenergic receptor antagonist

Journal of Medicinal Chemistry
L ZhengP Ernsberger

Abstract

New beta-adrenergic receptor antagonists, 2-(R)-(+)- and 2-(S)-(-)-1-(9H-carbazol-4-yl-oxy)-3-[[1-(fluoromethyl)ethyl]amino ]-2-propanol ((S)- and (R)-fluorocarazolols), were labeled with fluorine-18 at the no-carrier-added level by reductive alkylation of desisopropylcarazolol (4-(2-hydroxy-3-amino-1-propoxy)carbazole) with [18F]fluoroacetone. The latter was prepared by nucleophilic substitution of fluoride on acetol tosylate and may serve as a useful synthetic precursor for other radiotracers. The radiochemical yield of [18F]fluorocarazolol (500-1200 Ci/mmol) from [18F]fluoride was 40 +/- 10% at the end of the 45 min synthesis. Chiral HPLC showed > 99% enantiomeric purity of 2-(S)- and 2-(R)-[18F]fluorocarazolols. The log P of fluorocarazolol was 2.2 at pH 7.4. The in vitro KD values of (S)- and (R)-fluorocarazolol for the beta-adrenergic receptor were measured in a rat heart preparation to be KD = 68 and 1128 pM, respectively. Biodistribution experiments in mice demonstrated specific beta-adrenergic receptor binding of (S)-[18F]fluorocarazolol. (R)-[18F]fluorocarazolol showed no observable specific binding to beta-receptors in vivo. The uptake of (R)-[18F]fluorocarazolol may therefore be used as an estimation of nonspecific ...Continue Reading

Citations

Feb 24, 2001·Medical & Biological Engineering & Computing·Raymond F MuzicM S Berridge
May 25, 2005·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·P H ElsingaWillem Vaalburg
Apr 12, 1996·Journal of Chromatography. B, Biomedical Applications·A Van WaardeW Vaalburg
May 7, 1998·European Journal of Pharmacology·A Van WaardeW Vaalburg
May 17, 2000·Pharmaceutica acta Helvetiae·V W PikeP G Camici
Aug 14, 2001·Journal of Chromatography. B, Biomedical Sciences and Applications·Raymond F MuzicM S Berridge
Aug 24, 2001·Nuclear Medicine and Biology·A R Studenov, M S Berridge
Oct 1, 2003·Clinical Positron Imaging : Official Journal of the Institute for Clinical P.E.T·P H ElsingaWillem Vaalburg
Jul 27, 2005·Journal of Cardiovascular Pharmacology·Cristian SalinasP Ernsberger
Sep 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Santosh Reddy AlluriKun-Eek Kil
Oct 22, 2020·Journal of Chromatography. a·Mohammad Mahdi Moein, Thuy A Tran

Related Concepts

Fluorocarazolol, (R-(R*, R*))-stereoisomer
Adrenergic beta-Antagonists
Brain
Carbazoles
Heart
Pulse Rate
Hydrogen-Ion Concentration
Isotope Labeling, Stable
Lung
Myocardium

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