Structure鈥揂ctivity Relationships in 1,4-Benzodioxan-Related Compounds. 11. Reversed Enantioselectivity of 1,4-Dioxane Derivatives in 伪1-Adrenergic and 5-HT1A Receptor Binding Sit
文摘
5-HT1A receptor and 伪1-adrenoreceptor (伪1-AR) binding sites recognized by the 1,4-dioxanes 2鈥?b>4 display reversed stereochemical requirements. (S)-2 proved to be a potent 5-HT1A receptor agonist highly selective over 伪1-AR subtypes. Chirality influenced the anticancer activity of 3 and 4 in human prostate cancer cells (PC-3): (R)-4, eutomer at the 伪1d-AR subtype, was the most potent. The decreased effect of 4 and (R)-4 in 伪1d-AR silenced PC-3 cells confirmed that their anticancer activity was 伪1d-AR-dependent.