Patent US2552169A successfully refreshed from Google Patents.
US4293549A
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Quinolinyl guanidines having antiinflammatory, analgesic or antipyretic activity
Assignee: Leo Pharma AS
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Filing: 1978-10-27
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Granted: 1981-10-06
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Expires: 1998-10-27
Abstract
Abstract This invention relates to new compounds, salts, complexes and acylated derivatives thereof, methods of producing said compounds, intermediates used in the method, pharmaceutical compositions containing the present compounds and methods of producing same, and a method of treating patients using the present compounds, having the general formula (I) ##STR1## in which R 1 represents hydrogen, alkyl, alkoxy, hydroxy, halogen, trifluoromethyl, or phenyl; R 2 represents hydrogen, alkyl, alkoxy, halogen, trifluoromethyl, or hydroxy; R 3 represents alkyl, cycloalkyl which can be further mono- or disubstituted with methyl or ethyl, phenyl or phenyl-alkyl, optionally being further substituted; and R 4 represents a 5- or 6-membered heterocyclic ring system containing at least one nitrogen atom and optionally further nitrogen, oxygen and/or sulphur atoms, said ring system optionally being further substituted; or said ring system optionally forming part of a larger fused ring system; and pharmaceutically acceptable, non-toxic salts, complexes and acylated derivatives thereof. The present compounds can be used in the therapy of rheumatoid arthritis, osteo-arthritis, and allied conditions in humans and domestic animals by enteral, parenteral or topical administration.
Inventors
- 👤 Schneur Rachlin
- 👤 Edoardo Arrigoni-Martelli
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 13:19
CPC Classifications
C; C07; C07D; C07D215/00; C07D215/02; C07D215/16; C07D215/38; C07D215/42; A; A61; A61P; A61P25/00; A61P25/04; A61P29/00
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
209 words
A compound of the formula I having anti-inflammatory, analgesic or antipyretic activity and characterized by its low acute toxicity and low gastro ulcerogenic activity ##STR77## in which R 1 represents hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy, halogen, trifluoromethyl, or phenyl; R 2 represents hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halogen, trifluoromethyl, or hydroxy; R 3 represents C 1 -C 18 -alkyl, C 3 -C 8 -cycloalkyl which is unsubstituted or mono- or di-substituted with methyl or ethyl, or phenyl or phenyl-C 1 -C 3 -alkyl in which the phenyl is unsubstituted or substituted with a methyl, methoxy, halo or trifluoromethyl group; and R 4 represents a heterocyclic ring system selected from thiazolinyl, thienyl, pyrryl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxaxolyl, isoxazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, triazinyl, oxazinyl, benzoxazolyl, benzothiazolyl and benzoimidazolyl, said ring system being unsubstituted or substituted with from 1 to 2 members of the group consisting of C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, carboxy, carbalkoxy, halogen, trifluoromethyl, hydroxy and mercapto; and pharmaceutically acceptable, non-toxic salts thereof, pharmaceutically-acceptable non-toxic metal complexes thereof or the products wherein the H of --NHR 4 is replaced by the acyl group of a carboxylic acid.
Claim 2
Dependent Claim
209 words
A compound of the formula I having anti-inflammatory, analgesic or antipyretic activity and characterized by its low acute toxicity and low gastro ulcerogenic activity ##STR77## in which R 1 represents hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy, halogen, trifluoromethyl, or phenyl; R 2 represents hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halogen, trifluoromethyl, or hydroxy; R 3 represents C 1 -C 18 -alkyl, C 3 -C 8 -cycloalkyl which is unsubstituted or mono- or di-substituted with methyl or ethyl, or phenyl or phenyl-C 1 -C 3 -alkyl in which the phenyl is unsubstituted or substituted with a methyl, methoxy, halo or trifluoromethyl group; and R 4 represents a heterocyclic ring system selected from thiazolinyl, thienyl, pyrryl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxaxolyl, isoxazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, triazinyl, oxazinyl, benzoxazolyl, benzothiazolyl and benzoimidazolyl, said ring system being unsubstituted or substituted with from 1 to 2 members of the group consisting of C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, carboxy, carbalkoxy, halogen, trifluoromethyl, hydroxy and mercapto; and pharmaceutically acceptable, non-toxic salts thereof, pharmaceutically-acceptable non-toxic metal complexes thereof or the products wherein the H of --NHR 4 is replaced by the acyl group of a carboxylic acid.
Claim 3
Dependent Claim
117 words
A compound of the formula I having anti-inflammatory, analgesic or antipyretic activity and characterized by its low acute toxicity and low gastro ulcerogenic activity ##STR78## in which R 1 represents hydrogen or C 1 -C 4 -alkyl; R 2 represents hydrogen or C 1 -C 4 -alkyl; R 3 represents tertiary C 4 -C 12 -alkyl, C 5 -C 7 -cycloalkyl or phenyl, and R 4 represents thiazolinyl, thienyl, pyrryl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxaxolyl, isoxazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, triazinyl, oxazinyl, benzoxazolyl, benzothiazolyl or benzoimidazolyl; and pharmaceutically acceptable, non-toxic salts thereof, pharmaceutically acceptable, non-toxic metal complexes thereof or the above products wherein the H of NHR 4 is replaced by acetyl or propionyl.
Claim 4
Dependent Claim
117 words
A compound of the formula I having anti-inflammatory, analgesic or antipyretic activity and characterized by its low acute toxicity and low gastro ulcerogenic activity ##STR78## in which R 1 represents hydrogen or C 1 -C 4 -alkyl; R 2 represents hydrogen or C 1 -C 4 -alkyl; R 3 represents tertiary C 4 -C 12 -alkyl, C 5 -C 7 -cycloalkyl or phenyl, and R 4 represents thiazolinyl, thienyl, pyrryl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxaxolyl, isoxazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, triazinyl, oxazinyl, benzoxazolyl, benzothiazolyl or benzoimidazolyl; and pharmaceutically acceptable, non-toxic salts thereof, pharmaceutically acceptable, non-toxic metal complexes thereof or the above products wherein the H of NHR 4 is replaced by acetyl or propionyl.
Claim 5
Dependent Claim
90 words
A compound of the formula I having anti-inflammatory, analgesic or antipyretic activity and characterized by its low acute toxicity and low gastro ulcerogenic activity ##STR79## in which R 1 represents hydrogen, methyl or ethyl; R 2 represents hydrogen; R 3 represents tert-butyl, tert-pentyl, cyclohexyl or phenyl; and R 4 represents 2-thiazolyl, 2-(4-methyl-thiazolyl), or 2-(5-methyl-1,3,4-thiadiazolyl); and pharmaceutically acceptable, non-toxic salts thereof, pharmaceutically acceptable, non-toxic copper, zinc, manganese, magnesium, iron and gold complexes thereof or the above products wherein the H of the group NHR 4 is replaced by acetyl or propionyl.
Claim 6
Dependent Claim
90 words
A compound of the formula I having anti-inflammatory, analgesic or antipyretic activity and characterized by its low acute toxicity and low gastro ulcerogenic activity ##STR79## in which R 1 represents hydrogen, methyl or ethyl; R 2 represents hydrogen; R 3 represents tert-butyl, tert-pentyl, cyclohexyl or phenyl; and R 4 represents 2-thiazolyl, 2-(4-methyl-thiazolyl), or 2-(5-methyl-1,3,4-thiadiazolyl); and pharmaceutically acceptable, non-toxic salts thereof, pharmaceutically acceptable, non-toxic copper, zinc, manganese, magnesium, iron and gold complexes thereof or the above products wherein the H of the group NHR 4 is replaced by acetyl or propionyl.
Claim 7
Dependent Claim
11 words
A compound of claim 3 in which R 1 is methyl.
Claim 8
Dependent Claim
46 words
A compound of formula I of claim 1, in the form of a mono- or di-salt with hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, nitric acid, carbonic acid, p-toluenesulfonic acid, methanesulfonic acid, formic acid, acetic acid, propionic acid, citric acid, tartaric acid or maleic acid.
Claim 9
Dependent Claim
34 words
A compound of formula I of claim 1, or its salt, in the form of a complex formed with a member selected from the group consisting of Cu-, Zn-, Mn-, Mg-, Fe- and Au-salts.
Claim 10
Dependent Claim
7 words
N-Cyclohexyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 11
Dependent Claim
7 words
N-Cyclohexyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 12
Dependent Claim
7 words
N-tert-butyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 13
Dependent Claim
7 words
N-tert-butyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 14
Dependent Claim
7 words
N-tert-butyl-N"-4-(2-methylquinolyl)-N'-2-thiazolinylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 15
Dependent Claim
7 words
N-tert-butyl-N"-4-(2-methylquinolyl)-N'-2-thiazolinylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 16
Dependent Claim
7 words
N"-4-(2-Methylquinolyl)-N-tert-pentyl-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 17
Dependent Claim
7 words
N"-4-(2-Methylquinolyl)-N-tert-pentyl-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 18
Dependent Claim
7 words
N-tert-Butyl-N"-4-(2-methylquinolyl)-N'-2-(4-methylthiazolyl)guanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 19
Dependent Claim
7 words
N-tert-Butyl-N"-4-(2-methylquinolyl)-N'-2-(4-methylthiazolyl)guanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 20
Dependent Claim
7 words
N"-4-(2-Methylquinolyl)-N-phenyl-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 21
Dependent Claim
7 words
N"-4-(2-Methylquinolyl)-N-phenyl-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 22
Dependent Claim
7 words
N-Acetyl-N'-cyclohexyl-N"-4-(2-methylquinolyl)-N-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 23
Dependent Claim
7 words
N-Acetyl-N'-cyclohexyl-N"-4-(2-methylquinolyl)-N-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 24
Dependent Claim
7 words
N-Isobutyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 25
Dependent Claim
7 words
N-Isobutyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 26
Dependent Claim
7 words
N-Cycloheptyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 27
Dependent Claim
7 words
N-Cycloheptyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine and pharmaceutically acceptable, non-toxic salts thereof.
Claim 28
Dependent Claim
53 words
A pharmaceutical composition in dosage unit form for enteral, parenteral or topical treatment of humans or domestic animals suffering from arthritic diseases, which comprises as an active ingredient 0.01 g to 1 g of a compound as claimed in claim 1 calculated as the free base together with a pharmaceutically acceptable, non-toxic carrier.
Claim 29
Dependent Claim
46 words
A pharmaceutical composition in dosage unit form as claimed in claim 16 for oral treatment of humans or domestic animals in which the active ingredient is present in an amount of from 0.025 g to 0.5 g of the active ingredient, calculated as the free base.
Claim 30
Dependent Claim
43 words
A pharmaceutical composition in dosage unit form as claimed in claim 17 wherein the active component is the compound N-cyclohexyl-N"-4-(2-methylquinolyl)-N'-2-thiazolylguanidine or a pharmaceutically acceptable, non-toxic salt thereof, non-toxic metal complex thereof, or the products obtained by acylating said thiazolylguanidine with a carboxylic acid.
Claim 31
Dependent Claim
20 words
A pharmaceutical preparation in dosage unit form as claimed in claim 18 in the form of tablets, pills or capsules.
Claim 32
Dependent Claim
76 words
A pharmaceutical composition in dosage unit form for parenteral treatment of humans or domestic animals suffering from arthritic diseases comprising, as an active ingredient, from 0.1 g to 1 g of a compound as claimed in claim 1, calculated as the free base, as such or in the form of one of its non-toxic salts, non-toxic metal complexes or the products obtained by acylating said compound with a carboxylic acid, together with a pharmaceutically acceptable carrier.
Claim 33
Dependent Claim
39 words
A pharmaceutical composition comprising, as an active ingredient, a compound as claimed in claim 1 together with a carrier, the active ingredient being present in an amount from 0.1% to 95%, calculated as the free base, of said composition.
Claim 34
Dependent Claim
29 words
A pharmaceutical composition as claimed in claim 19 wherein the active ingredient is present together with a further antiinflammatory, analgetic or anti-pyretic agent, and a pharmaceutically acceptable, non-toxic carrier.
Claim 35
Dependent Claim
39 words
A pharmaceutical composition in dosage unit form as claimed in claim 20 for enteral and parenteral treatment of humans or domestic animals comprising from 0.01 g to 1 g in total of said active ingredient present in the composition.
Claim 36
Dependent Claim
49 words
A composition for topical treatment in the form of a powder or an ointment or cream comprising at least one compound as defined in claim 1 in an amount of from 0.5 g to 10 g per 100 g of the preparation, together with an inert pharmaceutically acceptable carrier.
Claim 37
Dependent Claim
47 words
In the treatment of humans or domestic animals suffering from arthritic diseases, the administration of a compound as claimed in claim 1, alone or in combination with another active ingredient, in daily doses from 1 mg/kg body weight/day to 30 mg/kg body weight/day of the active ingredient(s).
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-10-05 | 1985-04-06 | 1985-10-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-10-05 | 1989-04-06 | 1989-10-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-10-05 | 1993-04-06 | 1993-10-06 | $7700.00 | Window Closed / Lapsed |