US3984552A
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6-Oxo-7-substituted and 7,7-disubstituted-6H-indeno-[5,4-b]furan (and thiophene) carboxylic acids
Assignee: Merck and Co Inc
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Filing: 1975-02-24
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Granted: 1976-10-05
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Expires: 1995-02-24
Abstract
Abstract 6-Oxo-7,7-disubstituted-1,2,7,8-tetrahydro (and 7,8-dihydro)-6H-indeno-[5,4-b]furan (and thiophene)carboxylic acids, the salt, ester and amide derivatives thereof and combinations of these compounds with antikaluretic agents are disclosed having diuretic-saluretic, uricosuric and antihypertensive activity.
Inventors
- 👤 Edward J. Cragoe, Jr.
- 👤 Otto W. WOLTERSDORF, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 16:58
CPC Classifications
C; C07; C07D; C07D333/00; C07D333/50; C07D333/78; A; A61; A61P; A61P19/00; A61P19/06; A61P7/00; A61P7/10; C07C; C07C45/00; C07C45/61; C07C45/67; C07C45/673; C07C45/68; C07C45/70; C07C45/71; C07C49/00; C07C49/587; C07C49/703; C07C49/747; C07C49/753; C07C49/755; C07C49/76; C07C49/84; C07D307/00; C07D307/77; C07D307/93
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
86 words
A compound having the formula: ##SPC14## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof.
Claim 2
Dependent Claim
86 words
A compound having the formula: ##SPC14## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof.
Claim 3
Dependent Claim
15 words
A compound according to claim 1 wherein the 1,2-position is unsaturated and A is oxygen.
Claim 4
Dependent Claim
57 words
The compound of claim 1 wherein the 1,2-position is saturated; A is oxygen; R is phenyl, chlorophenyl or thienyl; R 1 is methyl; X 1 is chloro or methyl; X 2 is hydrogen, chloro or methyl; and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof.
Claim 5
Dependent Claim
19 words
The compound of claim 3 which is 4,5-di-chloro-6-oxo-7-methyl-7-phenyl-1,2,7,8-tetrahydro-6H-indeno[5,4-b]furan-2-carboxylic acid and its nontoxic pharmaceutically acceptable salt, ester and amide derivatives.
Claim 6
Dependent Claim
12 words
The compound of claim 4 which is the α-diasteriomer of 4,5-dichloro-6-oxo-7-methyl-7-phenyl-1,2,7,8-tetrahydro-6H-indeno[5,4-b]furan-2-carboxylic acid.
Claim 7
Dependent Claim
12 words
The compound of claim 4 which is the β-diasteriomer of 4,5-dichloro-6-oxo-7-methyl-7-phenyl-1,2,7,8-tetrahydro-6H-indeno[5,4-b]furan-2-carboxylic acid.
Claim 8
Dependent Claim
19 words
The compound of claim 3 which is 4,5-dichloro-6-oxo-7-methyl-7-(p-chlorophenyl)-1,2,7,8-tetrahydro-6H-indeno[5,4-b]furan-2-carboxylic acid and its nontoxic pharmaceutically acceptable salt, ester and amide derivatives.
Claim 9
Dependent Claim
19 words
The compound of claim 3 which is 4,5-dichloro-6-oxo-7-methyl-7-thienyl-1,2,7,8-tetrahydro-6H-indeno[5,4-b]furan-2-carboxylic acid and its nontoxic pharmaceutically acceptable salt, ester and amide derivatives.
Claim 10
Dependent Claim
111 words
A pharmaceutical composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula: ##SPC15## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof; and a pharmaceutically acceptable carrier.
Claim 11
Dependent Claim
111 words
A pharmaceutical composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula: ##SPC15## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof; and a pharmaceutically acceptable carrier.
Claim 12
Dependent Claim
127 words
A composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula: ##SPC16## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituents is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 50:1 to 1:1.
Claim 13
Dependent Claim
127 words
A composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula: ##SPC16## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituents is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 50:1 to 1:1.
Claim 14
Dependent Claim
133 words
A composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula: ##SPC17## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl having 1 to 6 carbon atoms; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 25:1 to 1:1.
Claim 15
Dependent Claim
133 words
A composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula: ##SPC17## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl having 1 to 6 carbon atoms; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 25:1 to 1:1.
Claim 16
Independent Claim
117 words
A method of treatment of edema associated with hypertension in a patient in need of said treatment comprising the oral administration of a therapeutically effective amount in unitary dosage form of a compound having the formula: ##SPC18## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof.
Claim 17
Independent Claim
117 words
A method of treatment of edema associated with hypertension in a patient in need of said treatment comprising the oral administration of a therapeutically effective amount in unitary dosage form of a compound having the formula: ##SPC18## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof.
Claim 18
Independent Claim
151 words
A method of treatment of edema associated with hypertension in a patient in need of said treatment comprising the oral administration of a therapeutically effective amount in a combination dosage form of a composition comprising an indenofuran or indenothiophene of the formula: ##SPC19## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl having 1 to 6 carbon atoms; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 50:1 to 1:1.
Claim 19
Independent Claim
151 words
A method of treatment of edema associated with hypertension in a patient in need of said treatment comprising the oral administration of a therapeutically effective amount in a combination dosage form of a composition comprising an indenofuran or indenothiophene of the formula: ##SPC19## wherein the dotted line indicates 1,2-saturated or unsaturated embodiments; A is oxygen or sulfur; R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo; R 1 is lower alkyl having 1 to 6 carbon atoms; X 1 is lower alkyl or halo; X 2 is hydrogen, lower alkyl or halo; and the non-toxic, pharmacologically acceptable salt lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 50:1 to 1:1.
Claim 20
Dependent Claim
10 words
The compound of claim 4 which is racemic 4,5-dichloro-6-oxo-7-methyl-7-phenyl-1,2,7,8-tetrahydro-6H-indeno[5,4-b]furan-2-carboxylic acid.
Claim 21
Dependent Claim
32 words
A composition according to claim 11 wherein the indenofuran is 4,5-dichloro-6-oxo-7-methyl-7-phenyl-1,2,7,8-tetrahydro-6H-indeno(5,4-b) furan-2-carboxylic acid and the mole ratio of the indenofuran to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride is in the ratio of from 10:1 to 2:1.
References Cited (Backward Citations)
US3931239A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-10-05 | 1980-04-05 | 1980-10-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-10-05 | 1984-04-05 | 1984-10-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-10-05 | 1988-04-05 | 1988-10-05 | $7700.00 | Window Closed / Lapsed |