Synthesis and Pharmacological Evaluation of Procaterol Derivatives Having a tert-Amino Group

A series of procaterol derivatives having a tert-amino group was synthesized. Among them, a morpholino derivative (4a, R1=H, NR2R3=morpholino) showed β-selective and rather potent adrenoceptor stimulant activities in an in vivo assay using anesthetized dogs. On the other hand, a morpholinopropanol analogue (4j, R1=CH3, NR2R3=morpholino) showed 400 times less potent bronchodilator activity than that of 4a. Some of the compounds showed weak bronchodilator activities and weak effects on the heart. It seems that steric hindrance around the nitrogen atom of catecholamines has a significant influence on β-adrenoceptor stimulant activities. Compound 4a also showed anti-allergic action estimated in terms of the inhibition of homologous passive cutaneous anaphlaxis in rats.