The synthesis of N-phenoxyethyl-1-substituted-1,2,3,4-tetrahydroisoquinolines and their α1-adrenoceptor blocking activity

A series of phenoxyisoquinolines, N-phenoxyethyl-1-(2-nitrophenyl)-1,2,3,4-THIQs 3a–3d, N-phenoxyethyl-1-benzyl-1,2,3,4-THIQ 3e, N-phenoxyethyl-1-(2-aminophenyl)-1,2,3,4-THIQs 5f–5i, N-phenoxyethyl-1-(2-phenoxyethylaminophenyl)-1,2,3,4-THIQs 5f′–5i′, have been synthesized and tested in isolated rat vas deferens α-adrenoreceptors. Comparison of pA2 values for these compounds in the presence of phenylephrine confirms that α1-adrenoceptor blocking activity of 3a–3d (–NO2 series) is more active than 6a–6c (–NH2 series) in the aortic rings isolated from SD rats. On the other hand, the electron-donating group at the 6-position of isoquinoline ring either increases or decreases the α1-adrenoceptor blocking activity.

Graphical abstractA series of phenoxyisoquinolines, N-phenoxyethyl-1-(2-nitrophenyl)-1,2,3,4-THIQs 3a–3d, N-phenoxyethyl-1-benzyl-1,2,3,4-THIQ 3e, N-phenoxyethyl-1-(2-aminophenyl)-1,2,3,4-THIQs 5f–5i, N-phenoxyethyl-1-(2-phenoxyethylaminophenyl)-1,2,3,4-THIQs 5f′–5i′, have been synthesized and tested in isolated rat vas deferens α-adrenoreceptors. Comparison of pA2 values for these compounds in the presence of phenylephrine confirms that α1-adrenoceptor blocking activity of 3a–3d (–NO2 series) is more active than 6a–6c (–NH2 series) in the aortic rings isolated from SD rats. On the other hand, the electron-donating group at the 6-position of isoquinoline ring either increases or decreases the α1-adrenoceptor blocking activity.Figure optionsDownload full-size imageDownload as PowerPoint slide