Cytotoxic steroids with antiestrogenic activity of the 11α-acyloxyestra-1,3,5(10)-triene series

Synthesis and Antiproliferative Activity of Some Androstene Oximes and Their O‐Alkylated Derivatives

“…Inhibition of specific enzymes like aromatase and 5α‐reductase are the frontline treatment approaches for breast and prostate carcinoma . Extensive chemical modifications of the steroid skeleton have been carried out to synthesize many potent antineoplastic agents, which could target hormone‐dependent cancers like prostate (e.g., finasteride, dutasteride), breast (e.g., exemestane), and uterine carcinomas .…”

Antitumor steroids: 1. Synthesis and biological activity of 11α-hydroxyestra-1,3,5(10)-triene derivatives with bis-(2-chloroethyl)amino-containing substituent at position 3

“…The data of elemental analyses coincide with the results of analytical calculations. Compounds VIc, VIIb, VIIc, and VIIIc were described in [19]; the synthesis of oxime Vd was described in [20].…”

“…Only the spectrum of compound IX, in which this substituent occurs at position 11, reveals a high-field shift of the signal from the geminale proton (H-11). The signals from protons of the substituent are displayed as multiplets of methylene protons (with d = 3.66 -3.75 ppm) and aromatic protons ( Table 2) [19].…”

Antitumor steroids: 2. Synthesis and biological activity of 11α-hydroxyestra-1,3,5,(10)-triene derivatives with bis-(2-chloroethyl)amino-containing substituents

“…Recently, we have demonstrated [1,2] that some steroids, representing esters of 11a-hydroxyestra-1,3,5(10)trienes with bis-(2-chlorethyl)amino-containing substituents at position 3, possess a rare but important combination of cytotoxicity and antiestrogen activity, which imparts to them high antitumor properties. The new compounds were synthesized on the basis of 11a-hydroxyestra-1,3,5(10)-trienes possessing an additional hydroxy group that significantly expanded possibilities of the proposed approach to the synthesis.…”

“…A comparison of the spectroscopic data for these compounds to those for the corresponding 3-regioisomers [1,2] shows that a change in position of the substituent containing bis-(2-chlorethyl)amino group in the molecule of steroid does not significantly influence the UV and IR absorption spectra. This bulky substituent also does not significantly modify the chemical shifts of signals from protons of the angular methyl group and 11-H in the 1 H NMR spectra, which are close even to those of 11a-hydroxyestra-1,3,5(10)-triene esters with small acyl radicals such as formates or acetates [1].…”