1,3-Dioxolane-Based Ligands as a Novel Class of Alpha1-Adrenoceptor Antagonists

1,3-Dioxolane-based compounds (2−14) were synthesized, and the pharmacological profiles at α1-adrenoceptor subtypes were assessed by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Compound 9, with a pA2 of 7.53, 7.36, and 8.65 at α1A, α1B, and α1D, respectively, is the most potent antagonist of the series, while compound 10 with a pA2 of 8.37 at α1D subtype and selectivity ratios of 162 (α1D/α1A) and 324 (α1D/α1B) is the most selective. Binding assays in CHO cell membranes expressing human cloned α1-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 α1-adrenoceptor antagonists.