STUDIES ON TETRAHYDROISOQUINOLINES (THI) (I) BRONCHODILATOR ACTIVITY AND STRUCTURE-ACTIVITY RELATIONSHIP

Abstract

For many years the synthesis of isoquinoline derivatives has been carried out in our Organic Chemistry Research Laboratory. In the process of pharmacological screening tests, 1-(3, 4-dihydroxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline was found to have significant bronchodilating as well as hypotensive actions, as briefly communicated in the previous report (1). This compound ha d been synthesized by Pyman in 1909 (2) and its hypotensive action was reported by Laidlaw in the following year (3). While our work was in progress, Holtz and his co-workers (4) demonstrated the formaton of this compound as a condensation product of dopamine and its enzymatically deaminated product, 3, 4-dihydroxyphenyl-acetaldehyde. They also reported its hypotensive and bronchodilating activities, which were interpreted as a β-sympathomimetic action of this compound. In reference to these studies 1-aralkyl derivatives of tetrahydroisoquinoline (THI) were synthesized and tested their bronchodilating activities. Among the compounds tested, 1-(3, 4, 5-trimthoxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline (IX) was observed to be the most active bronchodilator hitherto described in the literature. The relationship between the chemical structure and the bronchodilating activity was investigated in this paper.