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US4087526A
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(3-Amino-5-substituted-6-fluoropyrazinoyl or pyrazamido)-guanidines and their derivatives bearing substituents on the guanidino nitrogens
Assignee: Merck and Co Inc
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Filing: 1976-07-23
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Granted: 1978-05-02
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Expires: 1996-07-23
Abstract
Abstract This invention is concerned with (3-amino-5-substituted-6-fluoropyrazinoyl or pyrazinamido)guanidine compounds and derivatives thereof bearing substituents on the guanidine nitrogens. These compounds possess useful natriuretic properties. Also included are processes for preparing these compounds and a novel intermediate used in the preparation of these compounds.
Inventors
- 👤 Edward J. Cragoe, Jr.
- 👤 Otto W. WOLTERSDORF, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 18:59
CPC Classifications
C; C07; C07D; C07D241/00; C07D241/02; C07D241/10; C07D241/14; C07D241/24; C07D241/26; A; A61; A61P; A61P13/00; A61P13/02; A61P15/00
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
142 words
A compound of the formula: ##STR3## wherein R is amino, lower alkylamino having up to 5 carbon atoms, or diloweralkylamino having up to 5 carbon atoms; R 1 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 is hydrogen, lower alkyl having up to 5 carbon atoms, hydroxy ethyl, lower alkenyl having up to 3 carbon atoms, phenyl, benzyl or phenethyl, halo or lower alkyl substituted phenyl or halo or lower alkyl substituted benzyl or phenethyl; R 1 and R 2 are joined to form an alkylene bridge of 2 carbon atoms; R 3 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 and R 3 are joined to form a pyrrolidine or morpholine ring with the nitrogen atom to which they are attached; n is 0; and the non-toxic pharmaceutically acceptable salts thereof.
Claim 2
Dependent Claim
142 words
A compound of the formula: ##STR3## wherein R is amino, lower alkylamino having up to 5 carbon atoms, or diloweralkylamino having up to 5 carbon atoms; R 1 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 is hydrogen, lower alkyl having up to 5 carbon atoms, hydroxy ethyl, lower alkenyl having up to 3 carbon atoms, phenyl, benzyl or phenethyl, halo or lower alkyl substituted phenyl or halo or lower alkyl substituted benzyl or phenethyl; R 1 and R 2 are joined to form an alkylene bridge of 2 carbon atoms; R 3 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 and R 3 are joined to form a pyrrolidine or morpholine ring with the nitrogen atom to which they are attached; n is 0; and the non-toxic pharmaceutically acceptable salts thereof.
Claim 3
Dependent Claim
47 words
A compound of the formula: ##STR4## wherein R is amino, lower alkylamino wherein the alkyl can have from 1 to 5 carbon atoms, or diloweralkylamino wherein the alkyl group can have from 1 to 5 carbon atoms; n is 0 and the pharmaceutically acceptable non-toxic salts thereof.
Claim 4
Dependent Claim
47 words
A compound of the formula: ##STR4## wherein R is amino, lower alkylamino wherein the alkyl can have from 1 to 5 carbon atoms, or diloweralkylamino wherein the alkyl group can have from 1 to 5 carbon atoms; n is 0 and the pharmaceutically acceptable non-toxic salts thereof.
Claim 5
Dependent Claim
22 words
A compound of claim 2 wherein R is amino, and n is 0 thus forming (3,5-diamino-6-fluoropyrazinoyl)guanidine and the pharmaceutically acceptable non-toxic salts.
Claim 6
Dependent Claim
15 words
A compound of claim 3 wherein the salt is the hydrochloride, thus forming (3,5-diamino-6-fluoropyrazinoyl)guanidine hydrochloride.
Claim 7
Dependent Claim
22 words
A compound of claim 2 wherein R is dimethylamino, and n is 0, thus forming (3-amino-5-dimethylamino-6-fluoropyrazinoyl)guanidine and the pharmaceutically acceptable non-toxic salts.
Claim 8
Dependent Claim
22 words
A compound of claim 2 wherein R is isopropylamino, and n is 0, thus forming (3-amino-5-isopropylamino-6-fluoropyrazinoyl)guanidine and the pharmaceutically acceptable non-toxic salts.
Claim 9
Dependent Claim
148 words
A pharmaceutical composition consisting essentially of a compound of the formula: ##STR5## wherein R is amino, lower alkylamino having up to 5 carbon atoms, or diloweralkylamino having up to 5 carbon atoms; R 1 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 is hydrogen, lower alkyl having up to 5 carbon atoms, hydroxy ethyl, lower alkenyl having up to 3 carbon atoms, phenyl, benzyl or phenethyl, halo or lower alkyl substituted phenyl or halo or lower alkyl substituted benzyl or phenethyl; R 1 and R 2 are joined to form an alkylene bridge of 2 carbon atoms; R 3 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 and R 3 are joined to form a pyrrolidine or morpholine ring with the nitrogen atom to which they are attached; n is 0; and the non-toxic pharmaceutically acceptable salts thereof.
Claim 10
Dependent Claim
148 words
A pharmaceutical composition consisting essentially of a compound of the formula: ##STR5## wherein R is amino, lower alkylamino having up to 5 carbon atoms, or diloweralkylamino having up to 5 carbon atoms; R 1 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 is hydrogen, lower alkyl having up to 5 carbon atoms, hydroxy ethyl, lower alkenyl having up to 3 carbon atoms, phenyl, benzyl or phenethyl, halo or lower alkyl substituted phenyl or halo or lower alkyl substituted benzyl or phenethyl; R 1 and R 2 are joined to form an alkylene bridge of 2 carbon atoms; R 3 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 and R 3 are joined to form a pyrrolidine or morpholine ring with the nitrogen atom to which they are attached; n is 0; and the non-toxic pharmaceutically acceptable salts thereof.
Claim 11
Dependent Claim
46 words
A pharmaceutical composition consisting essentially of a compound of the formula: ##STR6## wherein R is amino, loweralkylamino or diloweralkylamino wherein the alkyl group can have from 1 to 5 carbon atoms; n is 0 and the pharmaceutically acceptable non-toxic salts thereof and an inert pharmaceutical carrier.
Claim 12
Dependent Claim
46 words
A pharmaceutical composition consisting essentially of a compound of the formula: ##STR6## wherein R is amino, loweralkylamino or diloweralkylamino wherein the alkyl group can have from 1 to 5 carbon atoms; n is 0 and the pharmaceutically acceptable non-toxic salts thereof and an inert pharmaceutical carrier.
Claim 13
Dependent Claim
19 words
A pharmaceutical composition according to claim 8 wherein the compound is (3,5-diamino-6-fluoropyrazinoyl)guanidine or a non-toxic pharmaceutically acceptable salt thereof.
Claim 14
Independent Claim
162 words
A method of treating edema and/or hypertension which consists essentially of administering to a patient in need of such treatment a compound of the formula: ##STR7## wherein R is amino, lower alkylamino having up to 5 carbon atoms, or diloweralkylamino having up to 5 carbon atoms; R 1 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 is hydrogen, lower alkyl having up to 5 carbon atoms, hydroxy ethyl, lower alkenyl having up to 3 carbon atoms, phenyl, benzyl or phenethyl, halo or lower alkyl substituted phenyl or halo or lower alkyl substituted benzyl or phenethyl; R 1 and R 2 are joined to form an alkylene bridge of 2 carbon atoms; R 3 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 and R 3 are joined to form a pyrrolidine or morpholine ring with the nitrogen atom to which they are attached; n is 0; and the non-toxic pharmaceutically acceptable salts thereof.
Claim 15
Independent Claim
162 words
A method of treating edema and/or hypertension which consists essentially of administering to a patient in need of such treatment a compound of the formula: ##STR7## wherein R is amino, lower alkylamino having up to 5 carbon atoms, or diloweralkylamino having up to 5 carbon atoms; R 1 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 is hydrogen, lower alkyl having up to 5 carbon atoms, hydroxy ethyl, lower alkenyl having up to 3 carbon atoms, phenyl, benzyl or phenethyl, halo or lower alkyl substituted phenyl or halo or lower alkyl substituted benzyl or phenethyl; R 1 and R 2 are joined to form an alkylene bridge of 2 carbon atoms; R 3 is hydrogen or lower alkyl having up to 5 carbon atoms; R 2 and R 3 are joined to form a pyrrolidine or morpholine ring with the nitrogen atom to which they are attached; n is 0; and the non-toxic pharmaceutically acceptable salts thereof.
Claim 16
Independent Claim
63 words
A method of treating edema and/or hypertension which consists essentially of administering to a patient in need of such treatment 5 mg./day to about 750 mg./day of a compound of the formula: ##STR8## wherein R is amino, lower alkylamino or diloweralkylamino wherein the alkyl group can have from 1 to 5 carbon atoms; n is 0 and the pharmaceutically acceptable non-toxic salts thereof.
Claim 17
Independent Claim
63 words
A method of treating edema and/or hypertension which consists essentially of administering to a patient in need of such treatment 5 mg./day to about 750 mg./day of a compound of the formula: ##STR8## wherein R is amino, lower alkylamino or diloweralkylamino wherein the alkyl group can have from 1 to 5 carbon atoms; n is 0 and the pharmaceutically acceptable non-toxic salts thereof.
Claim 18
Dependent Claim
23 words
A method of treatment according to claim 11 wherein the compound to be administered is (3,5-diamino-6-fluoropyrazinoyl)guanidine or a non-toxic pharmaceutically acceptable salt thereof.
References Cited (Backward Citations)
US3300494A
Cited
US3313813A
Cited
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 |