US4000294A
Expired / Lapsed
US
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Pyrazol-5-ones
Assignee: Bayer AG
•
Filing: 1975-11-14
•
Granted: 1976-12-28
•
Expires: 1995-11-14
Abstract
Abstract 1-Substituted pyrazole-5-ones of the formula ##STR1## and pharmaceutically acceptable, nontoxic salts thereof, wherein R is hydrogen or amino; R 1 is hydrogen, alkyl, alkenyl, unsubstituted or substituted aryl or unsubstituted or substituted aralky; X is A. ethylene, ethylene wherein 1 hydrogen atom on one of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by alkyl of 1 to 4 carbon atoms or said ethylene which is linked to R 2 via an oxygen or sulphur atom; B. propenyl, propenyl wherein 1 hydrogen atom on one, two or three of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, said propenyl being linked to the N 1 atom of the pyrazol ring via its methylene moiety; or C. methylene; Provided that when X is methylene, R 1 is not hydrogen if R is amino; R 2 is aryl unsubstituted or substituted by: A. 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, and lower alkoxy; B. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms; C. alkylamino, dialkylamino, cyano, trifluoromethoxy, nitro, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, or said carbamoyl wherein the nitrogen atom is a member of a heterocyclic ring, sulphamyl, alkylsulphamyl, dialkylsulphamyl, or said sulphamyl wherein the nitrogen is a member of a heterocyclic ring, or --SO n alkyl wherein n is 0, 1 or 2; D. alkylamino, dialkylamino, cyano, trifluoromethoxy, nitro, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, or said carbamoyl wherein the nitrogen atom is a member of a heterocyclic ring, sulphamyl, alkylsulphamyl, dialkylsulphamyl or said sulphamyl wherein the nitrogen is a member of a heterocyclic ring, or --SO n -- alkyl wherein n is 0, 1 or 2, and 1 or 2 of the same or different substituents selected from the group consisting of alkyl, alkenyl, alkoxy, halogen, and trifluoromethyl; or E. a fused, saturated or unsaturated 5-, 6-, or 7-membered ring or said ring containing 1 or 2 oxygen or sulphur atoms; are useful for their diuretic, saluretic, antihypertensive and antithrombotic effects.
Inventors
- 👤 Eike Moller
- 👤 Karl Meng
- 👤 Egbert Wehinger
- 👤 Harald Horstmann
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 16:22
CPC Classifications
C; C07; C07D; C07D231/00; C07D231/02; C07D231/10; C07D231/14; C07D231/44; C07D231/52
Claims Analysis
Total Claims: 42
Claim 1
Independent Claim
225 words
A pharmaceutical composition useful for effecting diuresis or saluresis in humans and animals and for treating hypertension in humans and animals which comprises a diuretically effective amount, a saluretically effective amount or an antihypertensive amount of a compound of the formula ##STR48## or a pharmaceutically acceptable nontoxic salt thereof, wherein R is amino; R 1 is hydrogen, lower alkyl or lower alkenyl; X is ethylene, ethylene wherein 1 hydrogen atom on 1 of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, linked to R 2 via an oxygen or sulphur atom; R 2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by: a. 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms and lower alkoxy; b. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5,6 or 7 carbon atoms; c. nitro or d. nitro, and 1 or 2 of the same or different substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkoxy, halogen and trifluoromethyl in combination with a pharmaceutically-acceptable, nontoxic, inert diluent or carrier.
Claim 2
Dependent Claim
225 words
A pharmaceutical composition useful for effecting diuresis or saluresis in humans and animals and for treating hypertension in humans and animals which comprises a diuretically effective amount, a saluretically effective amount or an antihypertensive amount of a compound of the formula ##STR48## or a pharmaceutically acceptable nontoxic salt thereof, wherein R is amino; R 1 is hydrogen, lower alkyl or lower alkenyl; X is ethylene, ethylene wherein 1 hydrogen atom on 1 of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, linked to R 2 via an oxygen or sulphur atom; R 2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by: a. 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms and lower alkoxy; b. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5,6 or 7 carbon atoms; c. nitro or d. nitro, and 1 or 2 of the same or different substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkoxy, halogen and trifluoromethyl in combination with a pharmaceutically-acceptable, nontoxic, inert diluent or carrier.
Claim 3
Dependent Claim
106 words
A composition according to claim 1 wherein R 2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by: a. 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms; b. nitro or c. nitro, and 1 or 2 of the same or different substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkoxy of 2 to 4 carbon atoms, halogen and trifluoromethyl.
Claim 4
Dependent Claim
104 words
A composition according to claim 1 wherein R 1 is hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms; and R 2 is phenyl; naphthyl; or phenyl substituted by: a. 1 or 2 straight or branched-chain alkyl moieties of 1 to 8 carbon atoms, or alkenyl moieties of 2 to 8 carbon atoms; b. 1 or 2 alkoxy moieties of 1 to 6 carbon atoms; c. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms; d. 1 or 2 halogens; e. 1 or 2 trifluoromethyl moieties; or f. nitro.
Claim 5
Dependent Claim
108 words
A composition according to claim 1 wherein R 1 is hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms; and R 2 is phenyl; naphthyl; or phenyl substituted by: a. 1 or 2 straight or branched-chain alkyl moieties of 1 to 4 carbon atoms or alkenyl moieties of 2 to 4 carbon atoms; b. 1 or 2 alkoxy moieties of 1 to 4 carbon atoms; c. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms; d. 1 or 2 fluoro, chloro or bromo moieties; e. 1 or 2 trifluoromethyl moieties; or f. nitro.
Claim 6
Dependent Claim
102 words
A composition according to claim 1 wherein R 1 is hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms; and R 2 is phenyl; naphthyl; or phenyl substituted by: a. 1 or 2 members selected from the group consisting of straight or branched-chain alkyl and trifluoromethyl moieties of 1 to 4 carbon atoms; b. alkoxy of 1 to 4 carbon atoms; c. cycloalkyl of 5 or 6 carbon atoms; d. 1 or 2 fluoro, chloro, bromo or iodo moieties; e. chloro or bromo and alkyl of 1 or 2 carbon atoms, trifluoromethyl; or f. nitro.
Claim 7
Dependent Claim
119 words
A composition according to claim 1 wherein R 1 is hydrogen, methyl or ethyl; X is ethylene, ethylene wherein 1 hydrogen atom on one of the carbon atoms is substituted by alkyl of 1 or 2 carbons or ethylene wherein 1 hydrogen atom on each of the two carbon atoms are substituted by alkyl of 1 or 2 carbon atoms, linked to R 2 via an oxygen or sulphur atom; and R 2 is phenyl; naphthyl; or phenyl substituted by fluorine, chlorine, bromine, iodine, trifluoromethyl, nitro, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cyclohexyl, dichlorine, chlorine and methyl, chlorine and bromine, chlorine and fluorine, chlorine and trifluoromethyl, dibromine or methyl and trifluoromethyl.
Claim 8
Dependent Claim
53 words
A composition according to claim 6 wherein X is ethylene, ethylene where 1 hydrogen on one of the carbon atoms is substituted by methyl or ethyl or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by methyl, linked to R 2 via an oxygen or sulphur atom.
Claim 9
Dependent Claim
67 words
A composition according to claim 1 wherein R 1 is hydrogen or alkyl of 1 to 4 carbon atoms; X is ethylene or ethylene wherein 1 hydrogen atom on one of the carbon atoms is substituted by methyl, linked to R 2 via an oxygen or sulphur atom; and R 2 is phenyl; naphthyl; or phenyl substituted by 1 or 2 chlorine, methyl, ethyl or trifluoromethyl moieties.
Claim 10
Dependent Claim
70 words
A composition according to claim 1 wherein R 1 is hydrogen or alkyl of 1 to 4 carbon atoms; X is ethylene or ethylene wherein 1 hydrogen atom of one of the carbon atoms is substituted by methyl, linked to R 2 via an oxygen or sulphur atom; and R 2 is naphthyl; phenyl; or phenyl substituted by chlorine, methyl, trifluoromethyl, dichlorine, dimethyl, methyl and ethyl or methyl and trifluoromethyl.
Claim 11
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR49##
Claim 12
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR50##
Claim 13
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR51##
Claim 14
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR52##
Claim 15
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR53##
Claim 16
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR54##
Claim 17
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR55##
Claim 18
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR56##
Claim 19
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR57##
Claim 20
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR58##
Claim 21
Dependent Claim
11 words
A composition according to claim 1 wherein the compound is ##STR59##
Claim 22
Independent Claim
228 words
A method of effecting diuresis and saluresis in humans and animals and treating hypertension in humans and animals which comprises administering to such human or animal a diuretically effective amount, a saluretically effective amount or an antihypertensive amount of a compound of the formula or a pharmaceutically acceptable nontoxic salt thereof, wherein R is amino; R 1 is hydrogen, lower alkyl or lower alkenyl; X is ethylene, ethylene wherein 1 hydrogen atom on 1 of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, linked to R 2 via an oxygen or sulphur atom; R 2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by: a. 1 to 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms and lower alkoxy; b. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms; c. nitro; or d. nitro and 1 or 2 of the same or different substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkoxy, halogen and trifluoromethyl; in combination with a pharmaceutically-acceptable, nontoxic, inert diluent or carrier.
Claim 23
Independent Claim
228 words
A method of effecting diuresis and saluresis in humans and animals and treating hypertension in humans and animals which comprises administering to such human or animal a diuretically effective amount, a saluretically effective amount or an antihypertensive amount of a compound of the formula or a pharmaceutically acceptable nontoxic salt thereof, wherein R is amino; R 1 is hydrogen, lower alkyl or lower alkenyl; X is ethylene, ethylene wherein 1 hydrogen atom on 1 of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, linked to R 2 via an oxygen or sulphur atom; R 2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by: a. 1 to 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms and lower alkoxy; b. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms; c. nitro; or d. nitro and 1 or 2 of the same or different substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkoxy, halogen and trifluoromethyl; in combination with a pharmaceutically-acceptable, nontoxic, inert diluent or carrier.
Claim 24
Dependent Claim
106 words
A method according to claim 21 wherein R 2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by: a. 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms; b. nitro; or c. nitro and 1 or 2 of the same or different substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkoxy of 2 to 4 carbon atoms, halogen and trifluoromethyl.
Claim 25
Dependent Claim
104 words
A method according to claim 21 wherein R 1 is hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms; and R 2 is phenyl; naphthyl; or phenyl substituted by: a. 1 or 2 straight or branched-chain alkyl moieties of 1 to 8 carbon atoms, or alkenyl moieties of 2 to 8 carbon atoms; b. 1 or 2 alkoxy moieties or 1 to 6 carbon atoms; c. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms; d. 1 or 2 halogens; e. 1 or 2 trifluoromethyl moieties; or f. nitro.
Claim 26
Dependent Claim
107 words
A method according to claim 21 wherein R 1 is hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms; and R 2 phenyl; naphthyl; or phenyl substituted by: a. 1 or 2 straight or branched-chain alkyl moieties of 1 to 4 carbon atoms or alkenyl moieties of 2 to 4 carbon atoms; b. 1 or 2 alkoxy moieties of 1 to 4 carbon atoms; c. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms; d. 1 or 2 fluoro, chloro or bromo moieties; e. 1 or 2 trifluoromethyl moieties; or f. nitro.
Claim 27
Dependent Claim
102 words
A method according to claim 21 wherein R 1 is hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms; and R 2 is phenyl; naphthyl or phenyl substituted by: a. 1 or 2 members selected from the group consisting of straight or branched-chain alkyl and trifluoromethyl moieties of 1 to 4 carbon atoms; b. alkoxy of 1 to 4 carbon atoms; c. cycloalkyl of 5 or 6 carbon atoms; d. 1 or 2 fluoro, chloro, bromo or iodo moieties; e. chloro or bromo and alkyl of 1 or 2 carbon atoms, trifluoromethyl; or f. nitro.
Claim 28
Dependent Claim
119 words
A method according to claim 21 wherein R 1 is hydrogen, methyl or ethyl; X is ethylene, ethylele wherein 1 hydrogen atom on one of the carbon atoms is substituted by alkyl of 1 or 2 carbons or ethylene wherein 1 hydrogen atom on each of the two carbon atoms are substituted by alkyl of 1 or 2 carbon atoms, linked to R 2 via an oxygen or sulphur atom; and R 2 is phenyl; naphthyl; or phenyl substituted by fluorine, chlorine, bromine, iodine, trifluoromethyl, nitro, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cyclohexyl, dichlorine, chlorine and methyl, chlorine and bromine, chlorine and fluorine, chlorine and trifluoromethyl, dibromine or methyl and trifluoromethyl.
Claim 29
Dependent Claim
53 words
A method according to claim 21 wherein X is ethylene, ethylene wherein 1 hydrogen on one of the carbon atoms is substituted by methyl or ethyl or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by methyl, linked to R 2 via an oxygen or sulphur atom.
Claim 30
Dependent Claim
68 words
A method according to claim 21 wherein R 1 is hydrogen or alkyl or 1 to 4 carbon atoms; X is ethylene or ethylene wherein 1 hydrogen atom on one of the carbon atoms is substituted by methyl and linked to R 2 via an oxygen or sulphur atom; and R 2 is phenyl; naphthyl; or phenyl substituted by 1 or 2 chlorine, methyl, ethyl or trifluoromethyl moieties.
Claim 31
Dependent Claim
70 words
A method according to claim 21 wherein R 1 is hydrogen or alkyl of 1 to 4 carbon atoms; X is ethylene or ethylene wherein 1 hydrogen atom of one of the carbon atoms is substituted by methyl, linked to R 2 via an oxygen or sulphur atom; and R 2 is naphthyl; phenyl; or phenyl substituted by chlorine, methyl, trifluoromethyl, dichlorine, dimethyl, methyl and ethyl or methyl and trifluoromethyl.
Claim 32
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR60##
Claim 33
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR61##
Claim 34
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR62##
Claim 35
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR63##
Claim 36
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR64##
Claim 37
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR65##
Claim 38
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR66##
Claim 39
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR67##
Claim 40
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR68##
Claim 41
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR69##
Claim 42
Dependent Claim
11 words
A method according to claim 21 wherein the compound is ##STR70##
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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 |