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US 5,705,662 AGranted
17-(3-imino-2-alkylpropenyl)-5.beta., 14.beta.-androstane derivatives active on the cardiovascular system, processes for their preparation and pharmaceutical compositions containing same
AssigneeSigma-Tau Industrie Farmaceutiche Riunite S.p.A.
InventorsAlberto Cerri, Giuseppe Bianchi, Patrizia Ferrari, Piero Melloni, Maria Luisa Quadri
Life of this patent
Estimating the term…
Abstract
New 17-3-imino-2-alkyl propenyl!-14.beta.-hydroxy-5.beta.-androstane derivatives active on the cardiovascular system by inhibiting Na+,K+-ATPase, a process for their preparation, and to pharmaceutical compositions for the treatment of cardiovascular disorders, such as heart failure and hypertension.
Claims19
Stereoisomers, Z and E isomers and their mixtures, optical isomers and mixtures thereof and pharmaceutically acceptable salts of compounds of general formula (I):
- ##STR3## wherein:
- the symbol means .alpha. or .beta. configuration;
- the double bonds are in the E configuration;
- R.sup.1 represents hydrogen, C2-C4 alkyl unsubstituted or substituted by NR.sup.5 R.sup.6 wherein
- R.sup.5 and R.sup.6, which may be the same or different, represent hydrogen, C1-C4 alkyl,
- or R.sup.5 and R.sup.6, taken together with the nitrogen atom they are linked to, form a five- or six-membered saturated heterocyclic ring optionally containing one or more additional heteroatoms selected from oxygen and nitrogen;
- R.sup.2 represents hydrogen or hydroxy;
- R.sup.3 represents methyl, ethyl or n-propyl;
- and
- R.sup.4 represents NHC(.dbd.NR.sup.7)NR.sup.8 R.sup.9 or OR.sup.10 wherein
- R.sup.7 represents hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by NR.sup.5 R.sup.6, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- R.sup.8 and R.sup.9, which may be the same or different, represent hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by NR.sup.5 R.sup.6, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- R.sup.10 represents hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by one or more NR.sup.5 R.sup.6 or NHC(.dbd.NH)NH.sub.2, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- the symbol means Z or E configuration;
- or
- two of R.sup.7, R.sup.8, and R.sup.9, taken together with the heteroatoms they are linked to, form a five- or six- or seven-membered heterocyclic ring.
13 more elements
An 17-(3-I!imino-2-alkylpropenyl)-14.beta.-hydroxy-5.beta.-androstane derivative of general formula (I):
- ##STR4## wherein:
- the symbol means .alpha. or .beta. configuration;
- the double bonds are in the E configuration;
- R.sup.1 represents hydrogen, C2-C4 alkyl unsubstituted or substituted by NR.sup.5 R.sup.6 wherein
- R.sup.5 and R.sup.6, which may be the same or different, represent hydrogen, C1-C4 alkyl,
- or R.sup.5 and R.sup.6, taken together with the nitrogen atom they are linked to, form a five- or six-membered saturated heterocyclic ring optionally containing one or more additional heteroatoms selected from oxygen and nitrogen;
- R.sup.2 represents hydrogen or hydroxy;
- R.sup.3 represents methyl, ethyl or n-propyl;
- and
- R.sup.4 represents NHC(.dbd.NR.sup.7)NR.sup.8 R.sup.9 or OR.sup.10 wherein
- R.sup.7 represents hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by NR.sup.5 R.sup.6, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- R.sup.8 and R.sup.9, which may be the same or different, represent hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by NR.sup.5 R.sup.6, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- R.sup.10 represents hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by one or more NR.sup.5 R.sup.6 or NHC(.dbd.NH)NH.sub.2, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- the symbol means Z or E configuration;
- or
- two of R.sup.7, R.sup.8, and R.sup.9, taken together with the heteroatoms they are linked to, form a five- or six- or seven-membered heterocyclic ring.
13 more elements
A process, comprising condensing a compound of general formula (II);
- ##STR5## with a compound of general formula (III) or (IV):
- H.sub.2 NNHC(.dbd.NR.sup.7)NR.sup.8 R (III)
- H.sub.2 NOR.sup.10 (IV)
- to produce a compound of general formula (I):
- ##STR6## wherein:
- the symbol means .alpha. or .beta. configuration;
- the double bonds are in the E configuration;
- R.sup.1 represents hydrogen, C2-C4 alkyl unsubstituted or substituted by NR.sup.5 R.sup.6 wherein
- R.sup.5 and R.sup.6, which may be the same or different, represent hydrogen, C1-C4 alkyl,
- or R.sup.5 and R.sup.6, taken together with the nitrogen atom they are linked to, form a five- or six-membered saturated heterocyclic ring optionally containing one or more additional heteroatoms selected from oxygen and nitrogen;
- R.sup.2 represents hydrogen or hydroxy;
- R.sup.3 represents methyl, ethyl or n-propyl;
- and
- R.sup.4 represents NHC(.dbd.NR.sup.7)NR.sup.8 R.sup.9 or OR.sup.10 wherein
- R.sup.7 represents hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by NR.sup.5 R.sup.6, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- R.sup.8 and R.sup.9, which may be the same or different, represent hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by NR.sup.5 R.sup.6, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- R.sup.10 represents hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by one or more NR.sup.5 R.sup.6 or NHC(.dbd.NH)NH.sub.2, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- the symbol means Z or E configuration;
- or
- two of R.sup.7, R.sup.8, and R.sup.9, taken together with the heteroatoms they are linked to, form a five- or six- or seven-membered heterocyclic ring.
17 more elements
A pharmaceutical composition, comprising:
- (A) a compound of general formula (I):
- ##STR7## wherein:
- the symbol means .alpha. or .beta. configuration;
- the double bonds are in the E configuration;
- R.sup.1 represents hydrogen, C2-C4 alkyl unsubstituted or substituted by NR.sup.5 R.sup.6 wherein
- R.sup.5 and R.sup.6, which may be the same or different, represent hydrogen, C1-C4 alkyl,
- or R.sup.5 and R.sup.6, taken together with the nitrogen atom they are linked to, form a five- or six-membered saturated heterocyclic ring optionally containing one or more additional heteroatoms selected from oxygen and nitrogen;
- R.sup.2 represents hydrogen or hydroxy;
- R.sup.3 represents methyl, ethyl or n-propyl;
- and
- R.sup.4 represents NHC(.dbd.NR.sup.7)NR.sup.8 R.sup.9 or OR.sup.10 wherein
- R.sup.7 represents hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by NR.sup.5 R.sup.6, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- R.sup.8 and R.sup.9, which may be the same or different, represent hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by NR.sup.5 R.sup.6, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- R.sup.10 represents hydrogen, methyl or C2-C4 alkyl, where the C2-C4 alkyl is unsubstituted or substituted by one or more NR.sup.5 R.sup.6 or NHC(.dbd.NH)NH.sub.2, wherein R.sup.5 and R.sup.6 have the previously defined meanings;
- the symbol means Z or E configuration;
- or
- two of R.sup.7, R.sup.8, and R.sup.9, taken together with the heteroatoms they are linked to, form a five- or six- or seven-membered heterocyclic ring;
- and
- (B) a pharmaceutically acceptable carrier or diluent.
16 more elements
Dependencies are inferred from the claim text.