17Beta-CYANO-18A-HOMO-19-NOR-ANDROST-4-ENE DERIVATIVE, ITS USE AND MEDICAMENTS COMPRISING THE DERIVATIVE
The 17β-cyano-18a-homo-19-nor-androst-4-ene derivatives of the present invention possess gestagenic activity. They have the general chemical formula 1, in which Z is selected from the group comprising O, two hydrogen atoms, NOR and NNHSO 2 R, in which R is hydrogen or C 1 -C 4 -alkyl, R 4 is hydrogen or halogen, furthermore either: R 6a , R 6b together form methylene or 1,2-ethanediyl or R 6a is hydrogen and R 6b is selected from the group comprising hydrogen, methyl and hydroxymethylene, and R 7 is selected from the group comprising hydrogen, C 1 -C 4 -alkyl, C 2 -C 3 -alkenyl and cyclopropyl, or: R 6a is hydrogen and R 6b and R 7 either together form methylene or are omitted with formation of a double bond between C 6 and C 7 , R 9 , R 10 are hydrogen or are omitted with formation of a double bond between C 9 and C 10 , R 15 , R 16 are hydrogen or together form methylene, R 17 is selected from the group comprising hydrogen, C 1 -C 4 -alkyl and allyl, at least one of the substituents R 4 , R 6a , R 6b , R 7 , R 15 , R 16 and R 17 not being hydrogen or R 6b and R 7 being omitted with formation of a double bond between C 6 and C 7 or being omitted with formation of a double bond between C 1 and C 2 , and moreover comprise their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.
1 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative having the general chemical formula 1
where
Z is selected from the group comprising 0, two hydrogen atoms, NOR and NNHSO 2 R, in which R is hydrogen or C 1 -C 4 -alkyl,
R 2 is hydrogen or halogen,
furthermore either:
R 6a , R 6b together form methylene or 1,2-ethanediyl or R 6a is hydrogen and R 6b is selected from the group comprising hydrogen, methyl and hydroxymethylene, and
R 7 is selected from the group comprising hydrogen, C 1 -C 4 -alkyl, C 2 -C 3 -alkenyl and cyclopropyl,
or:
R 6a is hydrogen and R 6b and R either together form methylene or are omitted with formation of a double bond between C 6 and C 7 ,
R 9 , R 10 are hydrogen or are omitted with formation of a double bond between C 9 and C 10 ,
R 15 , R 16 are hydrogen or together form methylene,
R 17 is selected from the group comprising hydrogen, C 1 -C 4 -alkyl and allyl,
at least one of the substituents R 4 , R 6a , R 6b , R 7 , R 15 , R 16 and R 17 not being hydrogen or R 6b and R 7 being omitted with formation of a double bond between C 6 and C 7 or being omitted with formation of a double bond between C 1 and C 2 ,
and its solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.
2 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , characterized in that R 15 and R 16 together form methylene.
3 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , characterized in that Z is selected from the group comprising O, NOH and NNHSO 2 H.
4 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , characterized in that Z represents O.
5 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , characterized in that R 4 is hydrogen or chlorine.
6 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , characterized in that R 6a , R 6b together form 1,2-ethanediyl or are in each case hydrogen.
7 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , characterized in that R 7 is selected from the group comprising hydrogen and methyl.
8 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , characterized in that R 6b and R 7 together form methylene.
9 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , characterized in that R 17 is selected from the group comprising hydrogen and methyl.
10 . 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 , selected from the group comprising
17β-cyano-17α-methyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-6β-hydroxymethylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-6,6-ethanediyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-6β,7β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-6α,7α-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-methyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-ethyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7α-methyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7β-ethyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7α-ethyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-6β,7β; 15β,16β-bismethylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-6α,7α; 15β,16β-bismethylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7α-cyclopropyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7β-cyclopropyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-18a-homo-19-nor-androst-4,6-dien-3-one,
17β-cyano-15β,16β-methylene-18a-homo-19-nor-androsta-4,6-dien-3-one,
17β-cyano-7α-vinyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7β-vinyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-methyl-15β,16β-methylene-18a-homo-19-nor-androsta-4,6-dien-3-one,
17β-cyano-7α,17α-bismethyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7α-ethyl-17α-methyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7β-ethyl-17α-methyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-methyl-15β,16β-methylene-7α-vinyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-methyl-15β,16β-methylene-7β-vinyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7α-cyclopropyl-17α-methyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7β-cyclopropyl-17α-methyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-methyl-6β,7β-15β,16β-bismethylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-methyl-6α,7α-15β,16β-bismethylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-ethyl-15β,16β-methylene-18a-homo-19-nor-androsta-4,6-dien-3-one,
17β-cyano-17α-ethyl-7β-methyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-ethyl-7β-methyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7α-,17α-bisethyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7β,17α-bisethyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-ethyl-15β,16β-methylene-7α-vinyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-ethyl-15β,16β-methylene-7β-vinyl-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7α-cyclopropyl-17α-ethyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-7β-cyclopropyl-17α-ethyl-15β,16β-methylene-18a-homo-19-nor-androst-4-en-3-one,
17β-cyano-17α-ethyl-6β,7β-15β,16β-bismethylene-18a-homo-19-nor-androst-4-en-3-one and
17β-cyano-17α-ethyl-6α,7α-15β,16β-bismethylene-18a-homo-19-nor-androst-4-en-3-one.
11 . A method for oral contraception or for treatment of pre-, peri- and postmenopausal symptoms, comprising administering to a host in need thereof an effective amount of a 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 .
12 . A process according to claim 11 , characterized in that the medicament has gestagenic and antimineralcorticoid action.
13 . Medicament comprising at least one 17β-Cyano-18a-homo-19-nor-androst-4-ene derivative according to claim 1 and at least one suitable pharmaceutically harmless additive.
14 . Medicament according to claim 13 , moreover comprising at least one oestrogen.
15 . Medicament according to claim 14 , characterized in that the oestrogen is ethinylestradiol.
16 . Medicament according to claim 14 , characterized in that the oestrogen is a natural oestrogen.
17 . Medicament according to claim 16 , characterized in that the natural oestrogen is oestradiol.
18 . Medicament according to claim 16 , characterized in that the natural oestrogen is oestradiol valerate.
19 . Medicament according to claim 16 , characterized in that the natural oestrogen is a conjugated oestrogen.