Adrenerigic agents. 7.1 Synthesis and beta-adrenergic agonist activity of several 2-pyridylethanolamines.
Jen T, Frazee JS, Schwartz MS, Kaiser C.
In a search for new selective bronchodilators, three 2-pyridylethanolamines, i.e., 2-tert-butylamino-1-(5-hydroxy-2-pyridyl)ethanol (2b), a related 6-methylsulfonylmethyl (2c), and, a 6-methyl (2d) derivative, were prepared. These compounds were examined for potential bronchodilator activity in an in vitro test for relaxation of guinea pig tracheal tissue. Potential cardiac stimulant activity was evaluated in vitro by measuring changes in the rate of spontaneously beating guinea pig right atrial muscle. Comparison of potency in the tracheal test relative to that in the atrial procedure provides a measure of selectivity. Results of this study indicate that replacement of the phenyl ring of a para-hydroxylated phenylethanolamine with a 2-pyridyl system generally results in compounds which retain a high order of potency in the tracheal test; however, selectivity for tracheobronchial vs. cardiac tissue is markedly greater for the pyridyl derivatives. The alpha-picoline, 2-tert-butylamino-1-(5-hydroxy-6-methyl-2-pyridyl) ethanol (2d), which bears labile protons at a position meta to the ethanolamine side chain, was about equipotent with the corresponding 6-unsubstituted relative 2b. The reason for the failure of these apparently appropriately located labile protons to enhance beta-adrenoreceptor agonist activity is uncertain.