Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, 210009 Nanjing, P. R. China.
Chem Biodivers. 2011 Jun;8(6):1052-64. doi: 10.1002/cbdv.201000135.
According to a three-point pharmacophore for some uro-selective α(1) -adrenoceptor (AR) antagonists, a novel class of coumarin (=2H-1-benzopyran-2-one) derivatives have been successfully designed and synthesized with high efficacies for α(1) -AR. These synthesized coumarin derivatives exhibited high efficacies towards α(1) -AR in in vitro pharmacological assays. Compared with prazosin (pK(i) value of 8.77), among those coumarins, tolylpiperazine-substituted derivatives, 7 and 8, have comparable pK(i) values of 8.81 and 8.77, respectively. The trend in efficacies of these coumarin derivatives towards α(1A) -adrenoceptor was further rationalized by intensive molecular docking. Our work demonstrated that the designed coumarin derivatives can inhibit α(1) -AR in vitro. These findings will provide a guide for further studies of the medical therapy of benign prostatic hyperplasia (BPH).
根据一些尿选择性α1-肾上腺素能受体（AR）拮抗剂的三点药效基团，我们成功设计并合成了一类新型香豆素（=2H-1-苯并吡喃-2-酮）衍生物，对α1-AR 具有高效性。这些合成的香豆素衍生物在体外药理学测定中对α1-AR 表现出高效性。与哌唑嗪（pK(i) 值为 8.77）相比，在这些香豆素中，甲苯哌嗪取代的衍生物 7 和 8 的 pK(i) 值分别为 8.81 和 8.77，相当。通过深入的分子对接进一步合理化了这些香豆素衍生物对α1A-肾上腺素能受体的功效趋势。我们的工作表明，设计的香豆素衍生物可以在体外抑制α1-AR。这些发现将为良性前列腺增生（BPH）的医学治疗的进一步研究提供指导。
