US4089969A
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5-Aroyl-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: 1978-05-16
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Expires: 1997-02-23
Abstract
Abstract Novel 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid compounds represented by the formula <IMAGE> and the pharmaceutically acceptable, non-toxic esters and salts thereof, wherein R is hydrogen or a lower alkyl group containing from 1 to 4 carbon atoms and R1 is hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group of 1 to 4 carbon atoms, chloro, fluoro or bromo, the R1 substitution being at the ortho, meta or para positions of the aroyl group and process for the production of such compounds; 5-p-toluoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid is 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
2026-10-31 00:45
CPC Classifications
C; C07; C07D; C07D487/00; C07D487/02; C07D487/04; A; A61; A61P; A61P25/00; A61P25/04; A61P29/00; C07D207/00; C07D207/02; C07D207/30; C07D207/34
Claims Analysis
Total Claims: 49
Claim 1
Independent Claim
93 words
A compound selected from the group of those represented by the formula: ##STR8## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R represents hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta or para positions of the aroyl group.
Claim 2
Dependent Claim
93 words
A compound selected from the group of those represented by the formula: ##STR8## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R represents hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta or para positions of the aroyl group.
Claim 3
Dependent Claim
9 words
A compound of claim 1 wherein R is hydrogen.
Claim 4
Dependent Claim
9 words
A compound of claim 1 wherein R is methyl.
Claim 5
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is hydrogen, 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 6
Dependent Claim
11 words
An isopropyl ester of the compound of claim 4, isopropyl 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 7
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is o-methyl, 5-o-toluoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 8
Dependent Claim
11 words
An isopropyl ester of the compound of claim 6, isopropyl 5-o-toluoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 9
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is m-methyl, 5-m-toluoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 10
Dependent Claim
11 words
An isopropyl ester of the compound of claim 8, isopropyl 5-m-toluoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 11
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is p-methyl, 5-p-toluoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 12
Dependent Claim
11 words
An isopropyl ester of the compound of claim 10, isopropyl 5-p-toluoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 13
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is p-methoxy, 5-p-methoxybenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 14
Dependent Claim
11 words
An isopropyl ester of the compound of claim 12, isopropyl 5-p-methoxybenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 15
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is o-chloro, 5-o-chlorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 16
Dependent Claim
11 words
An isopropyl ester of the compound of claim 14, isopropyl 5-o-chlorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 17
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is m-chloro, 5-m-chlorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 18
Dependent Claim
11 words
An isopropyl ester of the compound of claim 16, isopropyl 5-m-chlorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 19
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is p-chloro, 5-p-chlorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 20
Dependent Claim
11 words
An isopropyl ester of the compound of claim 18, isopropyl 5-p-chlorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 21
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is p-fluoro, 5-p-fluorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 22
Dependent Claim
11 words
An isopropyl ester of the compound of claim 20, isopropyl 5-p-fluorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 23
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is o-fluoro, 5-o-fluorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 24
Dependent Claim
11 words
An isopropyl ester of the compound of claim 22, isopropyl 5-o-fluorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 25
Dependent Claim
14 words
A carboxylic acid compound of claim 3 wherein R 1 is p-fluoro, 5-p-fluorobenzoyl-1,2-dihydro-6-methyl-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 26
Dependent Claim
16 words
A sodium, potassium or calcium salt of the compounds according to Formula (A) of claim 1.
Claim 27
Dependent Claim
17 words
A sodium salt compound of claim 25 wherein R and R 1 are both hydrogen, sodium 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 28
Dependent Claim
15 words
A compound of claim 25 wherein R is methyl and R 1 is p-fluoro, sodium-5-p-fluorobenzoyl-1,2-dihydro-6-methyl-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 29
Dependent Claim
9 words
An (l)-acid isomer of Formula (A) of claim 1.
Claim 30
Dependent Claim
15 words
The compound of claim 28 wherein R and R 1 are both hydrogen, (l)-5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 31
Dependent Claim
16 words
The compound of claim 28 wherein R is methyl and R 1 is p-fluoro, (l)-5-p-fluorobenzoyl-1,2-dihydro-6-methyl-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 32
Dependent Claim
16 words
A sodium, potassium or calcium salt of an (l)-acid isomer of Formula (A) of claim 1.
Claim 33
Dependent Claim
17 words
The sodium salt compound of claim 31 wherein R and R 1 are both hydrogen, sodium (l)-5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 34
Dependent Claim
16 words
The compound of claim 31 wherein R is methyl and R 1 is p-fluoro, sodium (l)-5-benzoyl-1,2-dihydro-6-methyl-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 35
Dependent Claim
14 words
A dicyclohexylamine salt of the compound of claim 6, dicyclohexylamine salt of 5-o-toluoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 36
Dependent Claim
14 words
A dicyclohexylamine salt of the compound of claim 14, dicyclohexylamine salt of 5-o-chlorobenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 37
Dependent Claim
14 words
A carboxylic acid compound of claim 2 wherein R 1 is p-ethoxy, 5-p-ethoxybenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Claim 38
Dependent Claim
11 words
An isopropyl ester of the compound of claim 36, isopropyl 5-p-ethoxybenzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate.
Claim 39
Dependent Claim
118 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 formula: ##STR9## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta, or para positions of the aroyl group.
Claim 40
Dependent Claim
118 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 formula: ##STR9## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta, or para positions of the aroyl group.
Claim 41
Independent Claim
117 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 formula: ##STR10## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms, and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta, or para positions of the aroyl group.
Claim 42
Independent Claim
117 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 formula: ##STR10## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms, and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta, or para positions of the aroyl group.
Claim 43
Dependent Claim
121 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 formula: ##STR11## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta, or para positions of the aroyl group.
Claim 44
Dependent Claim
121 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 formula: ##STR11## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta, or para positions of the aroyl group.
Claim 45
Independent Claim
119 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 formula: ##STR12## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta, or para positions of the aroyl group.
Claim 46
Independent Claim
119 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 formula: ##STR12## and the pharmaceutically acceptable, non-toxic alkyl esters having from one to 12 carbon atoms and salts thereof, wherein R is hydrogen or a lower alkyl group having from 1 to 4 carbon atoms and R 1 represents hydrogen, a lower alkyl group having from 1 to 4 carbon atoms, a lower alkoxy group having from 1 to 4 carbon atoms, chloro, fluoro or bromo, the R 1 substitution being at the ortho, meta, or para positions of the aroyl group.
Claim 47
Dependent Claim
21 words
The method of claim 41 wherein said pregnant mammal is a woman who is not suffering from inflammation, pyrexia, or pain.
Claim 48
Dependent Claim
33 words
The method of claim 42 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 49
Dependent Claim
71 words
The method of claim 41 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)
US3206470A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-05-15 | 1981-11-14 | 1982-05-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-05-15 | 1985-11-14 | 1986-05-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-05-15 | 1989-11-14 | 1990-05-16 | $7700.00 | Window Closed / Lapsed |