11β-long-chain-substituted 19-nor-17α-pregna-1,3,5(10)-trien-17β-ols with a 21,16α-lactone ring

#This invention relates to new 11β-long-chain-substituted 19-nor-17α-pregna-1,3,5(10)-trien-17β-ols with a 21,16α-lactone ring, process for their production and pharmaceutical preparations that contain these compounds as well as the use of these compounds for the production of pharmaceutical agents.

#Estrogens exert their physiological action on receptor proteins, the estrogen receptors (ERs). In this case, these are nuclear-position transcription factors that can be activated by ligands. Until a few years ago, it was assumed that estrogens exert their action via a single receptor.

#Only since 1996 has it become known that two subtypes of the estrogen receptor exist (ERα and ERβ) (Kuiper et al., Proc. Natl. Acad. Sci. USA 93, 1996, 5925–5930). Both are distinguished in their expression pattern in different tissues. Thus, for example, ERβ predominates over ERα in the rat prostates, while ERα predominates in the rat uterus. Areas were identified in the brain in which in each case only one of the two ER subtypes is expressed (Shugrue et al., Steroids 61, 1996, 678–681; Li et al., Neuroendocrinology 66, 1997, 63–67). Both ERα and ERβ are expressed in bones (Kuiper et al., Frontiers in Neuroendocrinology 1998, 19: 253–286), blood vessels (Iafrati et al., Nature Med. 1997, 3: 545–48) and normal breast tissue (Gustafsson and Warner, J. Steroid Biochem. Mol. Biol. 74, 2000, 245–248).

#FIG. 1 illustrates results for compound 1) inhibiting the growth of MCF-7 breast cancer cells. [Key to FIG. 1:] Zellproliferation (% der Kontrolle mit E2)=Cell proliferation (% of the control with E2) Kontrolle [ohne E2]=Control [without E2 ] Kontrolle [mit 10—10 M E2]=Control [ with 10—10 M E2] Verbindung 1=Compound 1 Konzentration =Concentration Pharmaceutical Preparations and Indications

#The compounds of general formula II represent compounds with antiestrogenic action after peroral or parenteral administration.

#Moreover, the compounds according to the invention are pure antiestrogens.

#546 mg (53% of theory) of 3,17β-dihydroxy-11β-hexyl-19-nor-17α-pregna-1,3,5(10)-triene-21,16α-lactone is obtained from 2.5 mmol (1.14 g) of 11β-hexyl-17-oxo-estra-1,3,5(10)-triene-3,16α-diyl-diacetate.

#In addition, the following compounds are obtained analogously: 3,17β-Dihydroxy-11β-octyl-19-nor-17α-pregna-1,3,5(10)-triene-21,16α-lactone 3,17β-Dihydroxy-11β-decyl-19-nor-17α-pregna-1,3,5(10)-triene-21,16α-lactone 3,17β-Dihydroxy-11β-dodecyl-19-nor-17α-pregna-1,3,5(10)-triene-21,16α-lactone

#Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The preceding preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.