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Molecular structures of some D-homo-6-oxa-8α analogs of steroidal estrogens

“…The distance between the hydroxyl group at the C(3) atom and the oxygen of the carboxyl group of Glu353 according to the calculated data ~3.8 Å is much greater than in the complex with the natural hormone estradiol (2.4 Å) [28]. Eventually analysis the calculated value of the enthalpy of formation of the ligand in the complex with the receptor is approximately 10 kcal/mole higher than in the free state.…”

“…We will illustrate the results of modeling for the case of compound 4b, since estrogens with a hydroxyl group at the C(3) atom must have greater affinity for the respective receptors than the analogs with a methoxyl group [28]. In the complex of an estradiol with an estrogen α-receptor constructed from the data from X-ray 149 crystallographic analysis [29] the analog 4b was docked manually instead of the natural hormone.…”

New analogs of steroid estrogens

“…The study of the mechanism of the action of steroid estrogens mediated by their nuclear receptors made it possible to reveal numerous relations between the structure and the biologic properties of this hormone group [1][2][3][4][5], in particular, in the series of estrogens 8α-analogs [6][7][8][9][10]. The formation of an "active" complex between the estrogen α-receptor and the ligands of steroid character requires a precise orientation of the oxygen-containing substituents in the A and D rings with respect to the clusters Glu-353-Arg-394-water and His-524 respectively [11].…”