Adrenergic agents. 8. Synthesis and .beta.-adrenergic agonist activity of some 3-tert-butylamino-2-(substituted phenyl)-1-propanols

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Abstract
Replacement of the benzylic hydroxyl group of N-tert-butylnorepinephrine with a hydroxymethyl substituent afforded a propanolamine homolog which retained a high degree of .beta.-adrenergic agonist activity. As modification of the meta substituent of catecholic ethanolamines, such as N-tert-butylnorepinephrine, often provides compounds that exert a more pronounced effect in relaxing tracheobronchial smooth muscle (.beta.2-adrenergic agonist) than in stimulating cardiac muscle (.beta.1-adrenergic response), a series of 3-tert-butylamino-2-(3-substituted 4-hydroxyphenyl)-1-propanols was prepared. The 3-meta substituents included HOCH2, H2NCONH, MeSO2NH, H and NH2. These phenylpropanolamine derivatives were compared with their phenylethanolamine counterparts in in vitro tests that measure the ability of these compounds to relax spontaneously contracted guinea pig tracheal smooth muscle (a measure of potential bronchodilating activity) and to increase the rate of contraction of a spontaneously beating guinea pig right atrial preparation (an indicator of potential cardiac stimulating activity). All of the propanolamine derivatives were less potent than their ethanolamine relatives. In both series replacement of the catecholic m-hydroxyl group with the indicated substituents usually resulted in compounds with increased selectivity for tracheobronchial vs. cardiac muscle.

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