Synthesis and blocking activities of a new class of α₁-adrenoceptor antagonists

Finding effective chemotherapeutic agents for clinical use is a long-lasting goal in medicinal chemistry. In this study, we report a new class of α₁-adrenoceptor (α₁-AR) antagonists. Specifically, we describe the synthesis and the blocking activities toward α₁-AR of 7-(2-hydroxypropoxy)-3,4-dihydroisoquinolin-1(2H)-one 1 and its structurally perturbed analogs 2-11 that were designed according to the principle of bioisosterism. Their structures were identified with IR, (1) H NMR, MS, HRMS and elemental analysis. The blocking activities of compounds 1-11 were evaluated on isolated rat anococcygeus muscles. The results indicated that these compounds showed moderate to good activities. Among them, compound 1 exhibited the highest activity that was comparable to those of known α₁-AR antagonists tamsulosin and DDPH (1-(2,6-dimethylphenoxy)-2-(3,4-di- methoxyphenylethylamino)propane hydrochloride) and thus may be exploitable as a lead compound for the discovery of promising α₁-AR antagonists.