US4100294A
Expired / Lapsed
US
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5-(Hydroxy (substituted) methyl)-2,3-dihydrobenzo furan-2-carboxylic acid and its derivatives
Assignee: Merck and Co Inc
•
Filing: 1976-12-06
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Granted: 1978-07-11
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Expires: 1996-12-06
Abstract
Abstract 5-[Hydroxy(substituted)methyl]-2,3-dihydrobenzo-furan-2-carboxylic acids, the pharmaceutically acceptable 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.
- 👤 William Hoffman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 08:13
CPC Classifications
C; C07; C07D; C07D307/00; C07D307/77; C07D307/78; C07D307/79; C07D307/80; A; A61; A61P; A61P19/00; A61P19/06; A61P7/00; A61P7/10; A61P9/00; A61P9/12; C07D307/82; C07D307/84; C07D307/85
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
100 words
A compound having the formula: ##STR6## wherein X is halo, methyl or hydrogen; Y is halo or methyl and X and Y can be combined to form a hydrocarbylene radical of from 3 to 4 carbon atoms; R is phenyl or mono or disubstituted phenyl wherein the substituent is halo, methyl, trifluoromethyl or methoxy; benzyl or mono- or di-nuclear substituted benzyl wherein the substituent is halo, methyl, methoxy or trifluoromethyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, and 5-methyl-2-furyl, and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof.
Claim 2
Dependent Claim
100 words
A compound having the formula: ##STR6## wherein X is halo, methyl or hydrogen; Y is halo or methyl and X and Y can be combined to form a hydrocarbylene radical of from 3 to 4 carbon atoms; R is phenyl or mono or disubstituted phenyl wherein the substituent is halo, methyl, trifluoromethyl or methoxy; benzyl or mono- or di-nuclear substituted benzyl wherein the substituent is halo, methyl, methoxy or trifluoromethyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, and 5-methyl-2-furyl, and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof.
Claim 3
Dependent Claim
17 words
A compound of claim 1 wherein X is halo or methyl and Y is halo or methyl.
Claim 4
Dependent Claim
11 words
A compound of claim 2 wherein X nd Y are halo.
Claim 5
Dependent Claim
79 words
A compound of the formula ##STR7## wherein X is halo, methyl or hydrogen; Y is halo or methyl; X and Y can be combined to form a hydrocarbylene radical of from 3 to 4 carbon atoms; R is selected from the group consisting of 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, 5-methyl-2-furyl, phenyl, p-methoxyphenyl, p-chlorophenyl, benzyl and p-chlorobenzyl and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof.
Claim 6
Dependent Claim
79 words
A compound of the formula ##STR7## wherein X is halo, methyl or hydrogen; Y is halo or methyl; X and Y can be combined to form a hydrocarbylene radical of from 3 to 4 carbon atoms; R is selected from the group consisting of 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, 5-methyl-2-furyl, phenyl, p-methoxyphenyl, p-chlorophenyl, benzyl and p-chlorobenzyl and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof.
Claim 7
Dependent Claim
12 words
The compound of claim 4 wherein X and Y are both chloro.
Claim 8
Dependent Claim
21 words
A compound of claim 4 wherein X and Y are chloro and R is 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 2-furyl, 3-furyl or 5-methyl-2-furyl.
Claim 9
Dependent Claim
114 words
A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula of ##STR8## wherein X is halo, methyl or hydrogen; Y is halo or methyl, X and Y can be combined to form a hydrocarbylene radical of from 3 or 4 carbon atoms, R is phenyl or mono or disubstituted phenyl wherein the substituent is halo, methyl, trifluoromethyl or methoxy; benzyl or mono- or di-nuclear substituted benzyl wherein the substituent is halo, methyl, methoxy or trifluoromethyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, and 5-methyl-2-furyl, and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof and a pharmaceutically acceptable carrier.
Claim 10
Dependent Claim
114 words
A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula of ##STR8## wherein X is halo, methyl or hydrogen; Y is halo or methyl, X and Y can be combined to form a hydrocarbylene radical of from 3 or 4 carbon atoms, R is phenyl or mono or disubstituted phenyl wherein the substituent is halo, methyl, trifluoromethyl or methoxy; benzyl or mono- or di-nuclear substituted benzyl wherein the substituent is halo, methyl, methoxy or trifluoromethyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, and 5-methyl-2-furyl, and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof and a pharmaceutically acceptable carrier.
Claim 11
Dependent Claim
14 words
A pharmaceutical composition according to claim 7 wherein X and Y are both chloro.
Claim 12
Dependent Claim
71 words
A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula: ##STR9## wherein X is chloro; Y is chloro; and R is selected from the group consisting of 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, 5-methyl-2-furyl, phenyl, p-methoxyphenyl, p-chlorophenyl, benzyl and p-chlorobenzyl and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof and a pharmaceutically acceptable carrier.
Claim 13
Dependent Claim
71 words
A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula: ##STR9## wherein X is chloro; Y is chloro; and R is selected from the group consisting of 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, 5-methyl-2-furyl, phenyl, p-methoxyphenyl, p-chlorophenyl, benzyl and p-chlorobenzyl and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof and a pharmaceutically acceptable carrier.
Claim 14
Dependent Claim
13 words
A pharmaceutical composition of claim 9 wherein the said compound is 6,7-dichloro-2,3-dihydro-5-[hydroxy-(2-thienyl)methyl]-2-carboxylic acid.
Claim 15
Independent Claim
122 words
A method of treatment of edema associated with hypertension comprising the administration of a therapeutically effective amount in unitary dosage form of a compound having the formula of: ##STR10## wherein X is halo, methyl or hydrogen; Y is halo or methyl; X and Y can be combined to form a hydrocarbylene radical of from 3 to 4 carbon atoms; R is phenyl or mono or disubstituted phenyl wherein the substituent is halo, methyl, trifluoromethyl or methoxy; benzyl or mono- or di-nuclear substituted benzyl wherein the substituent is halo, methyl, methoxy or trifluoromethyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, and 5-methyl-2-furyl, and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof.
Claim 16
Independent Claim
122 words
A method of treatment of edema associated with hypertension comprising the administration of a therapeutically effective amount in unitary dosage form of a compound having the formula of: ##STR10## wherein X is halo, methyl or hydrogen; Y is halo or methyl; X and Y can be combined to form a hydrocarbylene radical of from 3 to 4 carbon atoms; R is phenyl or mono or disubstituted phenyl wherein the substituent is halo, methyl, trifluoromethyl or methoxy; benzyl or mono- or di-nuclear substituted benzyl wherein the substituent is halo, methyl, methoxy or trifluoromethyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, and 5-methyl-2-furyl, and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof.
Claim 17
Dependent Claim
45 words
A method of treatment of edema associated with hypertension according to claim 11 comprising the administration to a patient of from 0.01 mg. to 10 mg./kg. of body weight of the patient of a compound of claim 11 wherein X and Y are both chloro.
Claim 18
Independent Claim
86 words
A method of treatment of edema associated with hypertension comprising the administration to a patient of from 0.01 mg. to 10 mg./kg. of body weight of the patient of a compound having the formula: ##STR11## wherein X is chloro; Y is chloro; and R is selected from the group consisting of 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, 5-methyl-2-furyl, phenyl, p-methoxyphenyl p-chlorophenyl, benzyl and p-chlorobenzyl and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof.
Claim 19
Independent Claim
86 words
A method of treatment of edema associated with hypertension comprising the administration to a patient of from 0.01 mg. to 10 mg./kg. of body weight of the patient of a compound having the formula: ##STR11## wherein X is chloro; Y is chloro; and R is selected from the group consisting of 2-thienyl, 3-thienyl, 5-methyl-2-thienyl, 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl, 2-furyl, 3-furyl, 5-methyl-2-furyl, phenyl, p-methoxyphenyl p-chlorophenyl, benzyl and p-chlorobenzyl and the non-toxic pharmaceutically acceptable salt, lower alkyl ester and the mono or di lower alkyl, piperidine and morpholine amides thereof.
Claim 20
Dependent Claim
16 words
A method of treatment of claim 13 wherein the compound to be administered is 6,7-dichloro-2,3-dihydro-5-[hydroxy-(2-thienyl)methyl]benzofuran-2-carboxylic acid.
References Cited (Backward Citations)
DE2630800A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-07-10 | 1982-01-09 | 1982-07-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-07-10 | 1986-01-09 | 1986-07-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-07-10 | 1990-01-09 | 1990-07-11 | $7700.00 | Window Closed / Lapsed |