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US 6,723,715 B1Granted
14, 15-cyclopropanosteroids of the 19-norandrostane series, method for producing said compounds and pharmaceutical preparation containing said compounds
AssigneeSchering Corporation
InventorsSven Ring, Walter Elger, Guenter Kaufmann
Life of this patent
Estimating the term…
Abstract
The invention relates to the new 14,15-cyclopropanoandrosteroids of the 19-norandrostane series of the general formula (I) their synthesis and to pharmaceutical compositions containing these compounds. The compounds of formula (I) have an interesting, mixed androgen/gestagen profile, the androgenic or gestagenic activity predominating, depending on the substitution.
Claims21
14,15-cyclopranoandrostanes of the 19-norandrostane series of the formula (I)
- wherein R1 is a hydrogen atom, a hydroxy group, C1-10-alkyl, a C1-10-alkyloxy, a C1-15 acyloxy, a C4-15-aryloxy, a C7-15-aralkyloxy or a C7-15-alkylaryloxy group;
- R2 represents a hydrogen atom, a hydroxy group, a C1-10 alkyl group, a C1-10 acyl group, a C1-10 acyloxy group, a C6-15 aryl group, a C7-15 aralkyl group, a C7-15 alkylaryl group, a —(CH2)nCH2Y group with n=0, 1 or 2 and Y representing a halogen atom or a pseudohalogen;
- a (CH2)mCH═CH(CH2)pR6 group with m=0,1, 2 or 3 and p=0, 1 or 2 and R6 representing a hydrogen atom, a C1-10-alkyl group, a C6-15 aryl group, a C7-15 aralkyl group, a C7-15 alkylaryl group, a hydroxyl group, a C1-10 alkyloxy group, a C1-10 acyloxy group;
- a —(CH2)oC≡CR7 group with o=0, 1 or 2 and R7 representing a hydrogen atom, a halogen atom, a C1-10 alkyl group, a C6-15 aryl group, a C7-15 aralkyl group, a C7-15 alkylaryl group or a C1-10 acyl group;
- or
- R1 and R2 together represent a keto group, a methylene group, a difluoromethylene group or, with inclusion of C-17, a spirooxirane or a 2,2-dimethyl-1,3-dioxolane;
- R3 represents a hydrogen atom or an α-C1-10 alkyl group or β-C1-10 alkyl group;
- R4 represents a halogen atom, a pseudohalogen, a hydroxy group or a perfluoroalkyl group;
- R5 represents a C1-4 alkyl group,
- wherein an α-cyclopropane or a β-cyclopropane group is between C-14 and C-15;
- and wherein optionally a 9,10-double bond is present and optionally an 11,12-double bond is present,
- with the proviso that, if both the 9,10-double bond and the 11,12-double bond are present or if only the 11,12-double bond is present, then R4 can be a hydrogen atom in addition to said halogen atom, said pseudohalogen, said hydroxy group or said perfluoroalkyl group;
- and
- with the further proviso that, if R5 is a methyl group, then R4 can be a hydrogen atom in addition to said halogen atom, said pseudohalogen, said hydroxy group or said perfluoroalkyl group;
- or pharmaceutically tolerated salts thereof.
12 more elements
A 14,15-cyclopranoandrostane selected from the group consisting of
- 4-chloro-17β-hydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4-chloro-17α-hydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4-chloro-17β-hydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4-chloro-17α-hydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4-bromo-17β-hydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4-bromo-17α-hydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4-bromo-17β-hydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4-bromo-17α-hydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4-fluoro-17β-hydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4-fluoro-17α-hydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4-fluoro-17β-hydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4-fluoro-17α-hydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4,17β-dihydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4,17α-dihydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4,17β-dihydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4,17α-dihydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4-trifluoromethyl-17β-hydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4-trifluoromethyl-17α-hydroxy-14α,15α-methylene-estr-4-ene-3-one,
- 4-trifluoromethyl-17β-hydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 4-trifluoromethyl-17α-hydroxy-14β,15β-methylene-estr-4-ene-3-one,
- 17β-hydroxy-14α,15α-methylene-estra-4,9,11-triene-3-one,
- 17α-hydroxy-14α,15α-methylene-estra-4,9,11-triene-3-one,
- 17β-hydroxy-14β,15β-methylene-estra-4,9,11-triene-3-one and
- 17α-hydroxy-14β,15β-methylene-estra-4,9,11-triene-3-one.
21 more elements
Dependencies are inferred from the claim text.