US4087539A
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5-(2-Furoyl)-, 5-(2-thenoyl)-, 5-(3-furoyl)- and 5-(3-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid derivatives and process for the production thereof
Assignee: Syntex USA LLC
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Filing: 1977-02-23
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Granted: 1978-05-02
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Expires: 1997-02-23
Abstract
Abstract Novel 5-substituted-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid compounds represented by the formulas <IMAGE> (A) <IMAGE> (B) and the pharmaceutically acceptable, non-toxic esters and salts thereof, wherein X is oxygen or sulphur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R1 is hydrogen, methyl, chloro or bromo, the R1 substitution being at the 3, 4 or 5 positions of the furan or thiophene ring in the compounds of Formula (A), and process for the production thereof; 5-(2-thenoyl)-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acid and 5-(3-furoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid are representative of the class. These compounds, as the racemic mixture or the (1)-isomer, are useful as anti-inflammatory, analgesic and antipyretic agents and as smooth muscle relaxants.
Inventors
- 👤 Joseph M. Muchowski
- 👤 Arthur F. Kluge
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 11:27
CPC Classifications
C; C07; C07D; C07D487/00; C07D487/02; C07D487/04; C07D207/00; C07D207/02; C07D207/30; C07D207/34; C07D333/00; C07D333/02; C07D333/04; C07D333/26; C07D333/38
Claims Analysis
Total Claims: 44
Claim 1
Independent Claim
84 words
A compound selected from the group of those represented by the formulas: ##STR9## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulphur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4 or 5 positions of the furan or thiophene ring.
Claim 2
Dependent Claim
84 words
A compound selected from the group of those represented by the formulas: ##STR9## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulphur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4 or 5 positions of the furan or thiophene ring.
Claim 3
Dependent Claim
9 words
A compound of claim 1 wherein X is oxygen.
Claim 4
Dependent Claim
9 words
A compound of claim 1 wherein X is sulphur.
Claim 5
Dependent Claim
9 words
A compound of claim 1 wherein R is hydrogen.
Claim 6
Dependent Claim
9 words
A compound of claim 1 wherein R is methyl.
Claim 7
Dependent Claim
7 words
A compound of claim 2, Formula (A).
Claim 8
Dependent Claim
17 words
A carboxylic acid compound of claim 6 wherein R and R 1 are both hydrogen, 5-(2-furoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 9
Dependent Claim
11 words
An isopropyl ester of the compound of claim 7, isopropyl 5-(2-furoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]-pyrrole-1-carboxylate.
Claim 10
Dependent Claim
14 words
A compound of claim 6 wherein R is hydrogen and R 1 is methyl.
Claim 11
Dependent Claim
14 words
A compound of claim 6 wherein R is hydrogen and R 1 is chloro.
Claim 12
Dependent Claim
14 words
A compound of claim 6 wherein R is hydrogen and R 1 is bromo.
Claim 13
Dependent Claim
7 words
A compound of claim 3, Formula (A).
Claim 14
Dependent Claim
17 words
A carboxylic acid compound of claim 12 wherein R and R 1 are both hydrogen, 5-(2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 15
Dependent Claim
11 words
An ethyl ester of the compound of claim 13, ethyl 5-(2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]-pyrrole-1-carboxylate.
Claim 16
Dependent Claim
14 words
A compound of claim 12 wherein R is hydrogen and R 1 is methyl.
Claim 17
Dependent Claim
14 words
A compound of claim 12 wherein R is hydrogen and R 1 is chloro.
Claim 18
Dependent Claim
23 words
A carboxylic acid compound of claim 12 wherein the R 1 substitution is at the C-4 position of the thiophene ring, 5-(4-chloro-2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 19
Dependent Claim
11 words
An isopropyl ester of the compound of claim 17, isopropyl 5-(4-chloro-2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 20
Dependent Claim
23 words
A carboxylic acid compound of claim 16 wherein the R 1 substitution is at the C-5 position of the thiophene ring, 5-(5-chloro-2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 21
Dependent Claim
11 words
An isopropyl ester of the compound of claim 19, isopropyl 5-(5-chloro-2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 22
Dependent Claim
14 words
A compound of claim 12 wherein R is hydrogen and R 1 is bromo.
Claim 23
Dependent Claim
7 words
A compound of claim 2, Formula (B).
Claim 24
Dependent Claim
13 words
The carboxylic acid compound of claim 22 wherein R is hydrogen, 5-(3-furoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 25
Dependent Claim
7 words
A compound of claim 3, Formula (B).
Claim 26
Dependent Claim
13 words
The carboxylic acid compound of claim 24 wherein R is hydrogen, 5-(3-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 27
Dependent Claim
18 words
A sodium, potassium or calcium salt of the compounds according to Formulas (A) or (B) of claim 1.
Claim 28
Dependent Claim
23 words
A potassium salt compound of Formula (A) of claim 26 wherein R and R 1 are both hydrogen and X is sulfur, potassium-5-(2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate
Claim 29
Dependent Claim
11 words
An (l)-acid isomer of Formulas (A) or (B) of claim 1.
Claim 30
Dependent Claim
13 words
A compound of claim 28 wherein R and R 1 are both hydrogen.
Claim 31
Dependent Claim
14 words
The compound of Formula (A) of claim 29 wherein X is sulfur, (l)-5-(2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 32
Dependent Claim
18 words
A sodium, potassium or calcium salt of an (l)-acid isomer of Formulas (A) or (B) of claim 1.
Claim 33
Dependent Claim
24 words
The potassium salt compound of Formula (A) of claim 31 wherein R and R 1 are both hydrogen, and X is sulfur, potassium (l)-5-(2-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 34
Dependent Claim
109 words
A composition for treating inflammation, pain or pyrexia in mammals consisting essentially of a pharmaceutically acceptable non-toxic excipient and a therapeutically effective amount of the racemic mixture or the (l)-isomer of a compound represented by the formulas: ##STR10## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulfur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4, or 5 positions of the furan or thiophene ring.
Claim 35
Dependent Claim
109 words
A composition for treating inflammation, pain or pyrexia in mammals consisting essentially of a pharmaceutically acceptable non-toxic excipient and a therapeutically effective amount of the racemic mixture or the (l)-isomer of a compound represented by the formulas: ##STR10## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulfur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4, or 5 positions of the furan or thiophene ring.
Claim 36
Independent Claim
108 words
A method of treating inflammation, pain or pyrexia in mammals which comprises administering to a mammal suffering therefrom a therapeutically effective amount of the racemic mixture or the (l)-isomer of a compound represented by the formulas: ##STR11## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulfur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4, or 5 positions of the furan or thiophene ring.
Claim 37
Independent Claim
108 words
A method of treating inflammation, pain or pyrexia in mammals which comprises administering to a mammal suffering therefrom a therapeutically effective amount of the racemic mixture or the (l)-isomer of a compound represented by the formulas: ##STR11## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulfur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4, or 5 positions of the furan or thiophene ring.
Claim 38
Dependent Claim
112 words
A composition for administration to a pregnant mammal to delay onset of parturition consisting essentially of a pharmaceutically acceptable non-toxic excipient and a therapeutically effective amount of the racemic mixture or the (l)-isomer of a compound represented by the formulas: ##STR12## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulfur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4, or 5 positions of the furan or thiophene ring.
Claim 39
Dependent Claim
112 words
A composition for administration to a pregnant mammal to delay onset of parturition consisting essentially of a pharmaceutically acceptable non-toxic excipient and a therapeutically effective amount of the racemic mixture or the (l)-isomer of a compound represented by the formulas: ##STR12## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulfur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4, or 5 positions of the furan or thiophene ring.
Claim 40
Independent Claim
110 words
A method comprising administering to a pregnant mammal to delay the onset of parturition a therapeutically effective amount of the racemic mixture or the (l)-isomer of a compound selected from the group of compounds represented by the formulas: ##STR13## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulfur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4, or 5 positions of the furan or thiophene ring.
Claim 41
Independent Claim
110 words
A method comprising administering to a pregnant mammal to delay the onset of parturition a therapeutically effective amount of the racemic mixture or the (l)-isomer of a compound selected from the group of compounds represented by the formulas: ##STR13## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein X is oxygen or sulfur, R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 is hydrogen, methyl, chloro or bromo, the R 1 substitution in the compounds of Formula (A) being at the 3, 4, or 5 positions of the furan or thiophene ring.
Claim 42
Dependent Claim
21 words
The method of claim 36 wherein said pregnant mammal is a woman who is not suffering from inflammation, pyrexia, or pain.
Claim 43
Dependent Claim
33 words
The method of claim 37 wherein said pregnant woman has had a previous spontaneous abortion, miscarriage or premature delivery, which occurred prior to the time for normal parturition at or about full term.
Claim 44
Dependent Claim
71 words
The method of claim 36 wherein said pregnant mammal is a woman who is not suffering from inflammation, pyrexia or nonparturition-causing pain but who is experiencing uterine muscle contractions, said compound being administered in a therapeutically effective amount adapted to reduce the intensity or duration of the uterine muscle contractions, stop the uterine muscle contractions altogether, whereby termination of the pregnancy is postponed from the time it otherwise would have happened.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-05-01 | 1981-10-31 | 1982-05-02 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-05-01 | 1985-10-31 | 1986-05-02 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-05-01 | 1989-10-31 | 1990-05-02 | $7700.00 | Window Closed / Lapsed |