Tritiation of two potent catecholamine beta-adrenergic receptor agonists
- PDF / 252,478 Bytes
- 4 Pages / 595.276 x 790.866 pts Page_size
- 64 Downloads / 182 Views
Tritiation of two potent catecholamine beta-adrenergic receptor agonists David G. Ahern • Demetri Orphanos Crist N. Filer
•
Received: 7 June 2013 / Published online: 3 August 2013 Ó Akade´miai Kiado´, Budapest, Hungary 2013
Abstract The tritiation of the beta-adrenergic catecholamines isoproterenol and hydroxybenzylisoproterenol is described. Keywords
Beta-adrenergic Tritium Tritium NMR
Introduction Even after decades of active investigation, the betaadrenergic receptor system still continues to reveal its intriguing biological complexity and fascinate medicinal chemists [1]. Extensively distributed throughout central and peripheral locations, beta-adrenergic receptors are active in such diverse functions as stimulation of pancreatic glucagon and insulin secretion as well as promoting glycogenolysis in the liver. Besides the obvious implications of this receptor family to cardiology [2], the beta-adrenergic receptor has now also been found to impact such important health areas as Alzheimer’s disease [3, 4] and oncology [5, 6]. Clearly, a detailed understanding of this influential receptor system is critically important. We have had a longstanding interest in the synthesis and characterization of tritiated agonists to advance the study of numerous important biological binding sites such as the dopamine [7–10], GABA [11], histamine [12], melatonin [13], opiate [14], serotonin [15], sigma-1 [16] and trace amine [17] receptors. In this paper we address the strategy of tritiating two structurally related and potent catecholamine agonists for the beta-adrenergic receptor. D. G. Ahern D. Orphanos C. N. Filer (&) PerkinElmer Life Sciences & Technology, Inc., 940 Winter St., Waltham, MA 02451, USA e-mail: [email protected]
Experimental Evaporations were carried out on a Buchi rotary evaporator at bath temperatures less than 40 °C. Analytical TLC autoradiography was performed on Analtech 5 9 15 cm glass plates coated with silica gel at 0 °C after spraying with PPO and exposing the plate to X-ray film. TLC plates were also scanned (*3 min) for applied radioactivity (*10 lCi). Analytical HPLC was performed on a PerkinElmer instrument with peak detection done simultaneously by UV and liquid scintillation flow monitor. Solution assays were performed with a PerkinElmer Tri-Carb 3100TR instrument. NMR spectra were obtained on a Bruker 300 MHz instrument and chemical shift values are expressed in parts per million (ppm) downfield from internal TMS. All chemicals used were reagent grade. [7-3H] (RS)-isoproterenol (3) by means of sodium borotritide To a solution of 23 mg (0.11 mmol) of isoproterenone free base (2, ICN Life Sciences 7409) in 1.5 mL of dimethylformamide was added 10 mg (0.22 mmol, 17.4 Ci) of high specific activity sodium borotritide in 1 mL of isopropanol in one portion at ambient temperature and rapid stirring was continued for 5 h. After this time the reaction was quenched by the addition of 0.2 mL of acetic acid. Labile tritium was then removed by several vacuum evaporations of methanol yieldi
Data Loading...
