The aim of this work was to study the ability of some estrogen 8α-analogues, that have CH3-group in the C-3 position, exhibit osteoprotective and cholesterolemic effects. The properties of these analogues was comparisoned with effects of native estradiol and 17α-ethynylestradiol (EE). We showed that compounds 3 ((d,l)-17β-acethoxy-3-methoxy-8α-estra-1,3,5(10)-triene) and 4 ((d,l)-3-methoxy-8α-estra-1,3,5(10)-triene-17-one) had the same osteoprotective and cholesterolemic effects as EE. The utherotropic effects of compound 3 and EE were the same, while the utherotropic activity of 17-keto derivative (compound 4) was higher than effect of EE. The osteoprotective and cholesterolemic effects of compounds 5 and 6 (d- or l-17β-acethoxy-3-methoxy-13-ethyl-8α-gone-1,3,5(10)-triene) were approximately the same, however the utherotropic action of these compounds was different: the compound 5 had significantly lower activity, but the compound 6 had the same effect in comparison with EE. Thus, all studied estrogen 8α-analogues may be used as basic constructions for structural modifications which is necessary as medications with while spectrum of biological properties.
Tsel'iu raboty byla proverka vozmozhnosti nekotorykh sintezirovannykh nami 8a-analogov steroidnykh éstrogenov, soderzhashchikh metoksil'nuiu gruppu pri S-3, proiavliat' osteoprotektornye i gipokholesterinemicheskie svoĭstva pri ponizhennoĭ gormonal'noĭ aktivnosti. Sopostavliali éffekty chetyrekh sintezirovannykh analogov so svoĭstvami prirodnogo shiroko ispol'zuemogo v klinike éstradiola – 17a-étiniléstradiola. Ustanovleno, chto analogi 3 (d,l-17b-atsetoksi-3-metoksi-8a-éstra-1,3,5(10)-trien) i 4 (d,l-3-metoksi-8a-éstra-1,3,5(10)-trien-17-on) proiavliaiut osteoprotektornuiu i gipokholesterinemicheskuiu aktivnost', sravnimuiu s aktivnost'iu étiniléstradiola. Uterotropnoe deĭstvie steroida 3 sopostavimo, a deĭstvie 17-ketoproizvodnogo (soedinenie 4) prevyshalo éffekt étiniléstradiola. Osteoprotektornaia i gipokholesterinemicheskaia aktivnosti soedineniĭ 5 i 6 (d- i l-formy 17b-atsetoksi-3-metoksi-13-étil-8a-gona-1,3,5(10)-trien) primerno odinakovy, odnako uterotropnoe deĭstvie steroida 5 po sravneniiu s étiniléstradiolom dostoverno nizhe, a u steroida 6 – skhodno s éffektom étiniléstradiola. Takim obrazom, vse izuchennye 8a-analogi éstrogenov mogut sluzhit' osnovoĭ dlia strukturnoĭ modifikatsii s tsel'iu sozdaniia veshchestv s rasshirennym spektrom biologicheskikh svoĭstv.
Keywords: osteoprotective and cholesterolemic effects; synthetic estrogen analogues.