17α-E-20-（杂芳基）去甲孕甾-1,3,5(10),20-四烯-3,17β-二醇[17α-（杂芳基）乙烯雌二醇]的合成与评价作为雌激素受体-α配体结合域（ERα-LBD）的配体。
Synthesis and evaluation of 17α-E-20-(heteroaryl)norpregn-1,3,5(10),20 tetraene-3,17β-diols [17α-(heteroaryl)vinyl estradiols] as ligands for the estrogen receptor-α ligand binding domain (ERα-LBD).
机构信息
Department of Chemistry, Augsburg College, 2211 Riverside Avenue, Minneapolis, MN 55454, USA.
出版信息
Bioorg Med Chem Lett. 2012 Jan 15;22(2):977-9. doi: 10.1016/j.bmcl.2011.12.003. Epub 2011 Dec 8.
Abstract
A series of 17α-(heteroaryl)vinyl estradiols was prepared to evaluate the influence of heteroatom on the affinity and efficacy of estrogenic ligands for the estrogen receptor-alpha ligand binding domain (ERα-LBD). The products demonstrated reduced binding affinity compared to the parent 17α-E-phenyl vinyl estradiol, but the binding was relatively independent of the heteroatom. The greatest influence of the heteroatom was evident in the efficacy of the compounds as the thienyl derivatives 2f,g were more potent than either the pyridyl 2b-d or pyrimidinyl 2e analogs. The results suggest that a subtle interplay of interactions between the ligands and the receptor influences the biological response.
摘要
一系列 17α-（杂芳基）乙烯雌二醇被制备出来，以评估杂原子对雌激素受体-α配体结合域（ERα-LBD）的雌激素配体的亲和力和效力的影响。与母体 17α-E-苯基乙烯雌二醇相比，这些产物的结合亲和力降低，但结合相对独立于杂原子。杂原子的最大影响表现在化合物的效力上，噻吩基衍生物 2f,g 比吡啶基 2b-d 或嘧啶基 2e 类似物更有效。结果表明，配体与受体之间相互作用的微妙相互作用影响着生物反应。
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