US4000125A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Novel cardiotonic steroids, process for their preparation and therapeutical use
Assignee: Siphar SA
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Filing: 1975-07-30
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Granted: 1976-12-28
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Expires: 1995-07-30
Abstract
Abstract The invention relates to novel steroid compounds having the formula ##STR1## and their glycoside derivatives containing a pyridazine ring, in which particularly the substituent R 4 is a hydroxy group or a hexopyranoside unit or a chain of two or three hexopyranoside units, as it is normally found in the molecule of the natural glycosides; one or even all the hydroxy groups contained in the R 4 can be either free or etherified or esterified with either a simple carboxylic acid or a carboxylic acid bearing basic groups, or even acetalized with an aldehyde or a ketone, depending on the position and the orientation of a pair of hydroxy groups. The subject compounds are endowed with cardiotonic activity. The invention moreover relates to the process for the preparation of the above compounds and to their therapeutic use.
Inventors
- 👤 Cesare Casagrande
- 👤 Giorgio Ferrari
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 16:13
CPC Classifications
C; C07; C07J; C07J43/00; C07J43/003
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
155 words
Novel cardiotonic steroid compounds and their glycoside derivatives containing a pyridazine ring, having the formula (1) ##STR12## in which R 1 and R 2 are hydrogen or a hydroxy group, either free or esterified with a carboxylic aliphatic acid selected from the group consisting of formic acid, acetic acid, propionic acid and butyric acid, R 3 is hydrogen or a hydroxy group and R 4 is a hydroxy group or a hexopyranoside unit or a chain of two or three hexopyranoside units, some or all of the hydroxy groups contained in the R 4 substituent being either free or etherified as the methyl ether, or esterified with formic acid, acetic acid, propionic acid or butyric acid or bearing basic groups, or when R 4 is a hexopyranoside unit or a chain of two or three hexopyranoside units having a pair of hydroxy groups in the positions 1, 2 or 1, 3 the acetal with acetone.
Claim 2
Dependent Claim
155 words
Novel cardiotonic steroid compounds and their glycoside derivatives containing a pyridazine ring, having the formula (1) ##STR12## in which R 1 and R 2 are hydrogen or a hydroxy group, either free or esterified with a carboxylic aliphatic acid selected from the group consisting of formic acid, acetic acid, propionic acid and butyric acid, R 3 is hydrogen or a hydroxy group and R 4 is a hydroxy group or a hexopyranoside unit or a chain of two or three hexopyranoside units, some or all of the hydroxy groups contained in the R 4 substituent being either free or etherified as the methyl ether, or esterified with formic acid, acetic acid, propionic acid or butyric acid or bearing basic groups, or when R 4 is a hexopyranoside unit or a chain of two or three hexopyranoside units having a pair of hydroxy groups in the positions 1, 2 or 1, 3 the acetal with acetone.
Claim 3
Dependent Claim
11 words
A compound according to claim 1, which is 3β, 14-dihydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 4
Dependent Claim
10 words
A compound according to claim 1, which is 3β-(tris-β-D-digitoxopyranosyloxy)-14-hydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 5
Dependent Claim
11 words
A compound according to claim 1, which is 3β-(tris-β-D-digitoxopyranosyloxy)-12β, 14-dihydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 6
Dependent Claim
11 words
A compound according to claim 1, which is 3β-(4'"-0-methyl-tris-β-0-digitoxopyranosyloxy)-12β, 14-dihydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 7
Dependent Claim
13 words
A compound according to claim 1, which is 3β, 5, 14, 19-tetrahydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 8
Dependent Claim
12 words
A compound according to claim 1, which is 3β-(α-L-rhamnopyranosyloxy)-5, 14, 19-trihydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 9
Dependent Claim
12 words
A compound according to claim 1, which is 3β-(α-L-3,4-0-isopropylidenrhamnopyranosyloxy)-5, 14, 19-trihydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 10
Dependent Claim
10 words
A compound according to claim 1, which is 3β-(α-L-thevetopyranosyloxy)-14-hydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 11
Dependent Claim
10 words
A compound according to claim 1, which is 3β-(α-L-2,4-0-diacetylthevetopyranosyloxy)-14-hydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 12
Dependent Claim
10 words
A compound according to claim 1, which is 3β-(α-L-2,4-0-diformylthevetopyranosyloxy)-14-hydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 13
Dependent Claim
10 words
A compound according to claim 1, which is 3β-(α-L-2,4-0-bis-(diethylaminoacetyl)-thevetopyranosyloxy)-14-hydroxy-17β-(4-pyridazinyl)-5β, 14β-androstane.
Claim 14
Dependent Claim
129 words
A process for the synthesis of the steroid compounds according to claim 1 comprising converting the furyl containing compound of formula (2) ##STR13## into the 2-substituted maleic dialdehyde, of formula (3), either in free form or acetalyzed, ##STR14## wherein R 7 represents one of the following groups: ##STR15## into the reaction of the compound (3) with hydrazine at a temperature of between 20° and 150° C, thus obtaining the corresponding compound of formula (1), said conversion being carried out by (a) electrolytical oxidation, (b) oxidation with bromine in alcoholic solution, (c) addition according to Diels-Alder of diethyl azodicarboxylate with subsequent acid hydrolysis under mild conditions, or (d) reaction with a N-halo-amide or -imide in the presence of an acceptor for hydrogen halide which is a weak base or buffer.
Claim 15
Dependent Claim
42 words
A process according to claim 13, characterized in that the conversion of the compound of formula (3) into that of formula (4) takes place through oxidation, either electrolytically or with bromine in alcoholic solution, followed by an acid hydrolysis under mild conditions.
Claim 16
Dependent Claim
38 words
A process according to claim 13, characterized in that the conversion of the compound of formula (3) into that of formula (4) takes place by addition according to Diels-Alder of diethyl-azodicarboxylate, and subsequent acid hydrolysis under mild conditions.
Claim 17
Dependent Claim
47 words
A process according to claim 13, characterized in that the conversion of the compound of formula (3) into that of formula (4) takes place by reaction with a N-halo-amide or -imide in the presence of an acceptor hydrogen halide, selected amongst weak bases and the buffer compounds.
Claim 18
Dependent Claim
25 words
A process according to claim 16, characterized in that as the N-halo-imide, N-bromo-succinimide is used, and as the hydrogen halide acceptor, sodium acetate is used.
Claim 19
Dependent Claim
22 words
A pharmaceutical composition having cardiotonic effect, characterized in that it contains, as the active ingredients, a compound according to the claim 1.
References Cited (Backward Citations)
US3838163A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-12-28 | 1980-06-28 | 1980-12-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-12-28 | 1984-06-28 | 1984-12-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-12-28 | 1988-06-28 | 1988-12-28 | $7700.00 | Window Closed / Lapsed |