Novel structural templates for estrogen-receptor ligands and prospects for combinatorial synthesis of estrogens

Abstract

Compounds such as these pyrazoles, which are novel ER ligands, are well suited for combinatorial synthesis using solid-phase methods.

Estrogen Receptor Alpha: Impact of Ligands on Intracellular Shuttling and Turnover Rate in Breast Cancer Cells

“…For instance, heavy metals (cadmium, nickel, copper, …) stimulate proliferation of uterine and mammary cells [34][35][36]. Since association of most estrogen derivatives with ER has been largely analyzed and commented [33,37,38], we will limit our review to compounds known to influence its turnover rate and shuttling properties, the topic of this paper.…”

“…Beside steroid hormones, potent estrogens include flavones, isoflavones and coumestanes (as prototypes of phytoestrogens [39]), as well as diphenylethylenic derivatives and analogues in the trans configuration (as prototypes of strong synthetic estrogens [38]). All these chemicals are linear, planar molecules (Fig.…”

“…This latter feature confers, upon binding, a "closed" conformation to the receptor [40]. This structural property distinguishes these strong ER agonists from a variety of angular ligands, gemdiphenylethylenes, triphenylethylenes, diarylimidazolines and diarylpiperazines [38,41,42], which maintain the ligandbinding pocket in an "open" conformation [43,44]. Linear, planar molecules are currently referred to as type I estrogens, while angular molecules are categorized as type II estrogens [ 45].…”

Molecular Design Based on Receptor-Independent Pharmacophore: Application to Estrogen Receptor Ligands

“…[29][30][31][32][33][34] Structurally diverse 60 environmental estrogens 27) are classified through QSAR studies. Groups of aro-matic, phenolic and aliphatic tetra substituted pyrazole, 35) raloxifene 36) and xenoestrogens are modeled for studying the SAR for binding affinity to the ER. Since the different classes of environmental estrogens examined contain no common structural elements, 3D roto translational descriptors 37) are employed to predict activity.…”

Pharmacological Profile of 6,12-Dihydro-3-methoxy-1-benzopyrano[3,4-b][1,4]benzothiazin-6-one, a Novel Human Estrogen Receptor Agonist.

“…Nonsteroidal estrogens are being increasingly developed and span a remarkable range of acyclic structures with a great variety of heterocycles. 18,19) This is the case of many natural derivatives with a coumarinic, flavone, or flavene core structure. 20) Among these natural phytoestrogens, coumestanes with a coumarinic structure are mainly represented by one derivative, coumestrol.…”