US4478837A
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3-Hydrazino cycloalkyl[c]pyridazines as antihypertensive agents
Assignee: Sandoz AG
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Filing: 1979-04-13
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Granted: 1984-10-23
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Expires: 1999-04-13
Abstract
Abstract Pharmaceutical compositions comprising as the active ingredient thereof an aminopyridazine derivative of the formula: ##STR1## wherein R 1 is amino, or ##STR2## wherein each of R 3 and R 4 is alkyl of 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are bound, form a cycloalkylidene radical of 5 to 12 carbon atoms, R 2 is hydrogen or methyl, A is --(CH 2 ) n --, wherein n is 0 or an integer from 1 to 7, or >N--CO--R 5 , wherein R 5 is alkyl of 1 to 16 carbon atoms, alkenyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, 1-adamantyl, or --(CH 2 ) m --R 6 , wherein m is 0 or an integer from 1 to 4, and R 6 is phenyl; phenyl monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms, alkylmercapto of 1 to 4 carbon atoms, or phenyl; phenyl substituted by two or three substitutents of the group chlorine, alkyl or alkoxy of 1 to 4 carbon atoms; diphenylmethyl, the phenyl rings of which may be monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms; or naphthyl, or --OR 7 , wherein R 7 is alkyl of 1 to 4 carbon atoms, or alkenyl of 2 to 4 carbon atoms or phenyl or phenalkyl, which may be monosubstituted on the phenyl ring by chlorine, alkyl or alkoxy of 1 to 4 carbon atoms, and in which the alkylene chain of phenylalkyl is of 1 to 4 carbon atoms, R 8 and R 9 are each hydrogen or alkyl of 1 to 4 carbon atoms, or a pharmaceutically acceptable acid addition salt thereof are useful in the treatment of hypertension.
Inventors
- 👤 Erhard Schenker
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 13:56
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/02; C07D471/04; C07D207/00; C07D207/02; C07D207/04; C07D207/06; C07D211/00; C07D211/04; C07D211/68; C07D211/72; C07D211/74; C07D211/76; C07D295/00; C07D295/02; C07D295/027; C07D295/033
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
332 words
A pharmaceutical composition useful in the treatment of hypertension comprising an antihypertensive effective amount of a compound of the formula: ##STR28## wherein R 1 is amino or ##STR29## wherein each of R 3 and R 4 is alkyl of 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are bound form cycloalkylidene of 5 to 12 carbon atoms, R 2 is hydrogen or methyl, A is --(CH 2 ) n -- wherein n is 0 or an integer from 1 to 7 or >N--CO--R 5 wherein R 5 is alkyl of 1 to 16 carbon atoms, alkenyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, 1-adamantyl, or --(CH 2 ) m --R 6 , wherein m is 0 or an integer from 1 to 4, and R 6 is phenyl; phenyl monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms, alkylmercapto of 1 to 4 carbon atoms, or phenyl; phenyl substituted by two or three substituents selected from the group consisting of chlorine, alkyl or alkoxy of 1 to 4 carbon atoms; diphenylmethyl, the phenyl rings of which may be monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms; or naphthyl or --OR 7 , wherein R 7 is alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms or phenyl or phenyl alkyl which may be monosubstituted on the phenyl ring by chlorine; alkyl or alkoxy or 1 to 4 carbon atoms, and in which the alkylene chain of phenylalkyl is of 1 to 4 carbon atoms, and R 8 and R 9 are each hydrogen or alkyl of 1 to 4 carbon atoms, provided that when R 6 is phenyl substituted with more than one tertiary butyl or tertiary butoxy, they are on other than adjacent carbon atoms, or pharmaceutically acceptable acid addition salts thereof in association with a pharmaceutical carrier.
Claim 2
Dependent Claim
332 words
A pharmaceutical composition useful in the treatment of hypertension comprising an antihypertensive effective amount of a compound of the formula: ##STR28## wherein R 1 is amino or ##STR29## wherein each of R 3 and R 4 is alkyl of 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are bound form cycloalkylidene of 5 to 12 carbon atoms, R 2 is hydrogen or methyl, A is --(CH 2 ) n -- wherein n is 0 or an integer from 1 to 7 or >N--CO--R 5 wherein R 5 is alkyl of 1 to 16 carbon atoms, alkenyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, 1-adamantyl, or --(CH 2 ) m --R 6 , wherein m is 0 or an integer from 1 to 4, and R 6 is phenyl; phenyl monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms, alkylmercapto of 1 to 4 carbon atoms, or phenyl; phenyl substituted by two or three substituents selected from the group consisting of chlorine, alkyl or alkoxy of 1 to 4 carbon atoms; diphenylmethyl, the phenyl rings of which may be monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms; or naphthyl or --OR 7 , wherein R 7 is alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms or phenyl or phenyl alkyl which may be monosubstituted on the phenyl ring by chlorine; alkyl or alkoxy or 1 to 4 carbon atoms, and in which the alkylene chain of phenylalkyl is of 1 to 4 carbon atoms, and R 8 and R 9 are each hydrogen or alkyl of 1 to 4 carbon atoms, provided that when R 6 is phenyl substituted with more than one tertiary butyl or tertiary butoxy, they are on other than adjacent carbon atoms, or pharmaceutically acceptable acid addition salts thereof in association with a pharmaceutical carrier.
Claim 3
Dependent Claim
24 words
A pharmaceutical composition according to claim 1, useful in the treatment of hypertension comprising 1.3 to 350 milligrams of the compound per unit dosage.
Claim 4
Dependent Claim
13 words
A pharmaceutical composition according to claim 1, in which R 1 is amino.
Claim 5
Dependent Claim
13 words
A pharmaceutical composition according to claim 1, in which R 1 is ##STR30##
Claim 6
Dependent Claim
16 words
A pharmaceutical composition according to claim 1, in which A is --(CH 2 ) n --.
Claim 7
Dependent Claim
14 words
A pharmaceutical composition according to claim 1, in which A is >N--COR 5 .
Claim 8
Dependent Claim
13 words
A pharmaceutical composition according to claim 1, in which the compound is 6-benzoyl-3-hydrazino-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine.
Claim 9
Dependent Claim
16 words
A pharmaceutical composition according to claim 1, in the form of a tablet, dragee or capsule.
Claim 10
Independent Claim
337 words
A method of treating hypertension in warm blooded animals which comprises orally administering to an animal in need of such treatment a therapeutically effective amount of a compound of the formula ##STR31## wherein R 1 is amino or ##STR32## wherein each of R 3 and R 4 is alkyl of 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are bound, form cycloalkylidene of 5 to 12 carbon atoms, R 2 is hydrogen or methyl, A is --(CH 2 ) n -- wherein n is 0 or an integer from 1 to 7 or >N--CO--R 5 wherein R 5 is alkyl of 1 to 16 carbon atoms, alkenyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, 1-adamantyl, or --(CH 2 ) m --R 6 , wherein m is 0 or an integer from 1 to 4, and R 6 is phenyl; phenyl monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms, alkyl-mercapto of 1 to 4 carbon atoms, or phenyl; phenyl substituted by two or three substituents selected from the group consisting of chlorine, alkyl or alkoxy of 1 to 4 carbon atoms; diphenylmethyl, the phenyl rings of which may be monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms; or naphthyl or --OR 7 , wherein R 7 is alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms or phenyl or phenylalkyl which may be monosubstituted on the phenyl ring by chlorine; alkyl or alkoxy of 1 to 4 carbon atoms, and in which the alkylene chain of phenylalkyl is of 1 to 4 carbon atoms, and R 8 and R 9 are each hydrogen or alkyl of 1 to 4 carbon atoms, provided that when R 6 is phenyl substituted with more than one tertiary butyl or tertiary butoxy, they are on other than adjacent carbon atoms, or a pharmaceutically acceptable acid addition salt thereof.
Claim 11
Independent Claim
337 words
A method of treating hypertension in warm blooded animals which comprises orally administering to an animal in need of such treatment a therapeutically effective amount of a compound of the formula ##STR31## wherein R 1 is amino or ##STR32## wherein each of R 3 and R 4 is alkyl of 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are bound, form cycloalkylidene of 5 to 12 carbon atoms, R 2 is hydrogen or methyl, A is --(CH 2 ) n -- wherein n is 0 or an integer from 1 to 7 or >N--CO--R 5 wherein R 5 is alkyl of 1 to 16 carbon atoms, alkenyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, 1-adamantyl, or --(CH 2 ) m --R 6 , wherein m is 0 or an integer from 1 to 4, and R 6 is phenyl; phenyl monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms, alkyl-mercapto of 1 to 4 carbon atoms, or phenyl; phenyl substituted by two or three substituents selected from the group consisting of chlorine, alkyl or alkoxy of 1 to 4 carbon atoms; diphenylmethyl, the phenyl rings of which may be monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms; or naphthyl or --OR 7 , wherein R 7 is alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms or phenyl or phenylalkyl which may be monosubstituted on the phenyl ring by chlorine; alkyl or alkoxy of 1 to 4 carbon atoms, and in which the alkylene chain of phenylalkyl is of 1 to 4 carbon atoms, and R 8 and R 9 are each hydrogen or alkyl of 1 to 4 carbon atoms, provided that when R 6 is phenyl substituted with more than one tertiary butyl or tertiary butoxy, they are on other than adjacent carbon atoms, or a pharmaceutically acceptable acid addition salt thereof.
Claim 12
Dependent Claim
19 words
A method according to claim 9, in which 5 to 700 milligrams of the compound are orally administered daily.
Claim 13
Dependent Claim
21 words
A method according to claim 9, in which 1.3 to 350 milligrams of the compound are administered orally per unit dose.
Claim 14
Dependent Claim
12 words
A method according to claim 9, in which R 1 is amino.
Claim 15
Dependent Claim
12 words
A method according to claim 9, in which R 1 is ##STR33##
Claim 16
Dependent Claim
15 words
A method according to claim 9, in which A is --(CH 2 ) n --.
Claim 17
Dependent Claim
13 words
A method according to claim 9 in which A is >N--COR 5 .
Claim 18
Dependent Claim
12 words
A method according to claim 9, in which the compound is 6-benzoyl-3-hydrazino-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine.
Claim 19
Dependent Claim
12 words
A method according to claim 9, in which the compound is 3-hydrazino-5,6,7,8-tetrahydro-6-(3-phenylpropionyl)pyrido[4,3-c]pyridazine.
References Cited (Backward Citations)
US3838125A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-10-23 | 1988-04-23 | 1988-10-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-10-23 | 1992-04-23 | 1992-10-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-10-23 | 1996-04-23 | 1996-10-23 | $7700.00 | Window Closed / Lapsed |