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

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• 作者：Alessandro Bonifazi ; Alessandro Piergentili ; Fabio Del Bello ; Yogita Farande ; Mario Giannella ; Maria Pigini ; Consuelo Amantini ; Massimo Nabissi ; Valerio Farfariello ; Giorgio Santoni ; Elena Poggesi ; Amedeo Leonardi ; Sergio Menegon ; Wilma Quaglia
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：January 24, 2013
• 年：2013
• 卷：56
• 期：2
• 页码：584-588
• 全文大小：216K
• 年卷期：v.56,no.2(January 24, 2013)
• ISSN：1520-4804

文摘

5-HT_1A 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-HT_1A 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.