Document Report Card

ID: ALA2311529

Journal: J Med Chem

Title: Structure-activity relationships in 1,4-benzodioxan-related compounds. 11. (1) reversed enantioselectivity of 1,4-dioxane derivatives in α1-adrenergic and 5-HT1A receptor binding sites recognition.

Authors: Bonifazi A, Piergentili A, Del Bello F, Farande Y, Giannella M, Pigini M, Amantini C, Nabissi M, Farfariello V, Santoni G, Poggesi E, Leonardi A, Menegon S, Quaglia W.

Abstract: 5-HT(1A) receptor and α(1)-adrenoreceptor (α(1)-AR) binding sites recognized by the 1,4-dioxanes 2-4 display reversed stereochemical requirements. (S)-2 proved to be a potent 5-HT(1A) receptor agonist highly selective over α(1)-AR subtypes. Chirality influenced the anticancer activity of 3 and 4 in human prostate cancer cells (PC-3): (R)-4, eutomer at the α(1d)-AR subtype, was the most potent. The decreased effect of 4 and (R)-4 in α(1d)-AR silenced PC-3 cells confirmed that their anticancer activity was α(1d)-AR-dependent.

CiteXplore: 23252794

DOI: 10.1021/jm301525w