Reversed- and normal-phase liquid chromatography in quantitative structure retention-property relationships of newly synthesized seco-androstene derivatives.

The rational preselection of drug candidates includes also correlation between physico-chemical properties (lipophilicity, as the key one) and pharmacokinetic properties, as well as pharmacodynamic activity. Lipophilicity can be determined alternatively by chromatographic methods. Chromatographic behavior of nineteen newly synthesized derivatives of 16-cyano-16,17-seco-5-androstene has been studied by reversed-phase and normal-phase thin-layer chromatography (RP- and NP-TLC).

HPTLC chromatography of androstene derivates. Application of normal phase thin-layer chromatographic retention data in QSAR studies.

The chromatographic behavior of seven 16-oximino derivatives of 3beta-hydropxy-5-androstene have been investigated using the normal-phase (NP) HPTLC chromatographic mode of the type silica-non-polar diluent (benzene)-polar modifier (acetonitrile, ethyl acetate, or dioxane). The linear relationship between the retention constants (R(M)) and the logarithm of the organic modifier content in the mobile phase allowed for the calculation of R(M)0 values. The influence of substituent in the molecule on extrapolated retention data is discussed.

Synthesis and anti-aromatase activity of some new steroidal D-lactones.

Starting from D-seco derivatives of 5-androstene 1-3, the D-homo lactones, 4 and 5, were synthesized. By the Oppenauer oxidation and/or by dehydration of 4 and 5 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil), the corresponding D-lactones 6-12 were obtained. The structures of 6 and 10 were unambiguously proved by the appropriate X-ray structural analysis.

Synthesis, X-ray crystal structures and biological activity of 16-amino-17-substituted-D-homo steroid derivatives.

D-Homo derivatives in the androstane and estrane series, 12-19, were synthesized by a fragmentation-cyclization reaction of 16-oximino-17-hydroxy-17-substituted derivatives 3-9, or by cyclization of the corresponding D-seco derivatives 20-26. The structures were confirmed by X-ray analysis of compounds 12 and 16. Preliminary assessment of inhibitory effects of D-homo derivatives from androstane series towards aromatase, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17 alpha-hydroxylase/C17-20 lyase (P450c17) and 17 beta-HSD indicated much lower inhibitory potential compared to previously tested activity of another type of D-modified steroids, namely D-seco derivatives.