PMID: 11931617Apr 5, 2002Paper

Structure-activity relationships in 1,4-benzodioxan-related compounds. 7. Selectivity of 4-phenylchroman analogues for alpha(1)-adrenoreceptor subtypes

Journal of Medicinal Chemistry
W QuagliaCarlo Melchiorre

Abstract

WB4101 (1)-related compounds 5-10 were synthesized, and their biological profile at alpha(1)-adrenoreceptor (AR) subtypes and 5-HT(1A) serotoninergic receptors was assessed by binding assays in Chinese hamster ovary and HeLa cell membranes expressing the human cloned receptors. Moreover, their receptor selectivity was further determined in functional experiments in isolated rat prostate (alpha(1A)), vas deferens (alpha(1A)), aorta (alpha(1D)), and spleen (alpha(1B)). In functional assays, compound 5 was the most potent at alpha(1D)-ARs with a reversed selectivity profile (alpha(1D) > alpha(1A) > alpha(1B)) relative to both prototype 1 and phendioxan (2) (alpha(1A) > alpha(1D) > alpha(1B)), whereas compound 8, bearing a carbonyl moiety at position 1, was the most potent at alpha(1A)-ARs with a selectivity profile similar to that of prototypes. The least potent of the series was the trans isomer 6, suggesting that optimum alpha(1)-AR blocking activity in this series is associated with a cis relationship between the 2-side chain and the 4-phenyl ring rather than a trans relationship as previously observed for the 2-side chain and the 3-phenyl ring in 2 and related compounds. Binding affinity results were not in complete agreement ...Continue Reading

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Citations

Jan 1, 2008·Acta Crystallographica. Section E, Structure Reports Online·Qing-Rong QiHu Zheng
Jan 1, 2008·Acta Crystallographica. Section E, Structure Reports Online·Li-Rong WenHuai-Yuan Xie
Jan 27, 2017·The Journal of Organic Chemistry·Pandi MuthupandiGovindasamy Sekar
Jan 4, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cleo S Evans, Lindsey O Davis
Jun 20, 2019·Organic & Biomolecular Chemistry·Thi Thu Huong LeDinh Hung Mac
Aug 9, 2003·Journal of Medicinal Chemistry·Donatella BoschiAmedeo Leonardi
Apr 4, 2003·Journal of Medicinal Chemistry·Livio BrasiliElena Poggesi
Nov 1, 2005·Bioorganic & Medicinal Chemistry·Gemma K KinsellaIsabel Rozas
Nov 30, 2019·The Journal of Organic Chemistry·Ryoga HojoMukund Jha
Aug 29, 2021·Medicinal Research Reviews·Kritika LaxmikeshavNagula Shankaraiah
Aug 10, 2006·Journal of the American Chemical Society·Wei WangLiansuo Zu

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