1,3-Dioxolane-based compounds (2-14) were synthesized, and the pharmacological profiles at R1-adrenoceptor subtypes were assessed by functional experiments in isolated rat vas deferens (R1A), spleen (R1B), and aorta (R1D). Compound 9, with a pA2 of 7.53, 7.36, and 8.65 at R1A, R1B, and R1D, respectively, is the most potent antagonist of the series, while compound 10 with a pA2 of 8.37 at R1D subtype and selectivity ratios of 162 (R1D/R1A) and 324 (R1D/R1B) is the most selective. Binding assays in CHO cell membranes expressing human cloned R1-adrenoceptor subtypes confirm the pharmacological profiles derived from functional experiments, although the selectivity values are somewhat lower. Therefore, it is concluded that 1,3-dioxolane-based ligands are a new class of R1-adrenoceptor antagonists
