Patent US4085211A successfully refreshed from Google Patents.
US4085211A
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Pyrazinecarboxamides and processes for preparing same
Assignee: Merck and Co Inc
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Filing: 1976-09-13
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Granted: 1978-04-18
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Expires: 1996-09-13
Abstract
Abstract The case involves novel pyrazinecarboxamides and processes for preparing same. The pyrazinecarboxamides are excellent eukalemic agents possessing diuretic and natriuretic properties.
Inventors
- 👤 Edward J. Cragoe, Jr.
- 👤 Otto W. WOLTERSDORF, Jr.
- 👤 Charles N. Habecker
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 18:26
CPC Classifications
C; C07; C07D; C07D241/00; C07D241/02; C07D241/10; C07D241/14; C07D241/24; C07D241/26; A; A61; A61P; A61P7/00; A61P7/10
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
255 words
A compound of the formula: ##STR7## wherein R 1 is hydrogen, lower alkyl having from 1 to 5 carbon atoms cycloalkyl having from 3 to 6 carbon atoms, lower alkenyl having from 2 to 3 carbon atoms; R 2 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 1 and R 2 are joined to form with the nitrogen atom to which they are attached a pyrrolidine or piperazine ring; R 3 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 4 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 5 is hydrogen, lower alkyl having 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; phenyl or substituted phenyl wherein the substituent is lower alkyl or halo; benzyl or phenethyl; trifluoroethyl, lower alkylamino, diloweralkylamino, allyl, propargyl, pyridyl, furfuryl, methoxy or hydroxy ethyl; ethoxy carbonyl methyl or carboxy methyl; R 6 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 10 nuclear carbon atoms; R 5 and R 6 are joined to form a piperazine or morpholine ring with the nitrogen atom to which they are attached; R 7 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 3 and R 7 are joined to form an alkylene bridge of 2 carbon atoms; X is halogen; and the pharmaceutically acceptable non-toxic acid addition salts thereof.
Claim 2
Dependent Claim
255 words
A compound of the formula: ##STR7## wherein R 1 is hydrogen, lower alkyl having from 1 to 5 carbon atoms cycloalkyl having from 3 to 6 carbon atoms, lower alkenyl having from 2 to 3 carbon atoms; R 2 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 1 and R 2 are joined to form with the nitrogen atom to which they are attached a pyrrolidine or piperazine ring; R 3 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 4 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 5 is hydrogen, lower alkyl having 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; phenyl or substituted phenyl wherein the substituent is lower alkyl or halo; benzyl or phenethyl; trifluoroethyl, lower alkylamino, diloweralkylamino, allyl, propargyl, pyridyl, furfuryl, methoxy or hydroxy ethyl; ethoxy carbonyl methyl or carboxy methyl; R 6 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 10 nuclear carbon atoms; R 5 and R 6 are joined to form a piperazine or morpholine ring with the nitrogen atom to which they are attached; R 7 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 3 and R 7 are joined to form an alkylene bridge of 2 carbon atoms; X is halogen; and the pharmaceutically acceptable non-toxic acid addition salts thereof.
Claim 3
Dependent Claim
60 words
A compound of the formula: ##STR8## wherein R 1 , R 3 , R 5 and R 7 are hydrogen; R 2 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 4 and R 6 are hydrogen or lower alkyl having from 1 to 3 carbon atoms; and the pharmaceutically acceptable non-toxic acid addition salts thereof.
Claim 4
Dependent Claim
60 words
A compound of the formula: ##STR8## wherein R 1 , R 3 , R 5 and R 7 are hydrogen; R 2 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 4 and R 6 are hydrogen or lower alkyl having from 1 to 3 carbon atoms; and the pharmaceutically acceptable non-toxic acid addition salts thereof.
Claim 5
Dependent Claim
34 words
A compound of claim 2 wherein R 1 , r 3 , r 5 and R 7 are hydrogen; R 2 is isopropyl; R 4 is methyl; R 6 is ethyl; which is 3-amino-5-isopropylamino-6-chloro-N-{[(ethylaminocarbonyl)amino](methylamino)methylene}-2-pyrazinecarboxamide.
Claim 6
Dependent Claim
32 words
A compound of claim 2 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are hydrogen which is 3,5-diamino-N-{[(aminocarbonyl)amino]aminomethylene}-6-chloro-2-pyrazinecarboxamide.
Claim 7
Dependent Claim
33 words
A compound of claim 2 wherein R 1 , r 2 , r 3 , r 5 , r 6 and R 7 are hydrogen; and R 4 is methyl; which is 3,5-diamino-N-{[(aminocarbonyl)amino](methylamino)methylene}-6-chloro-2-pyrazinecarboxamide.
Claim 8
Dependent Claim
34 words
A compound of claim 2 wherein R 1 , r 3 , r 5 , r 6 and R 7 are hydrogen; R 2 is isopropyl; and R 4 is methyl; which is 3-amino-5-isopropylamino-6-chloro-N-{[(aminocarbonyl)amino](methylamino)methylene}-2-pyrazinecarboxamide.
Claim 9
Dependent Claim
35 words
A compound of claim 2 wherein R 1 , r 2 , r 3 , r 4 , r 5 and R 7 are hydrogen; and R 6 is ethyl; which is 3,5-diamino-6-chloro-N{[(ethylaminocarbonyl)amino]aminomethylene}-2-pyrazinecarboxamide hydrochloride monohydrate.
Claim 10
Dependent Claim
34 words
A compound of claim 2 wherein R 1 , r 2 , r 3 , r 5 and R 7 are hydrogen; R 4 is methyl; and R 6 is ethyl; which is 3,5-diamino-6-chloro-N{[(ethylaminocarbonyl)amino](methylamino)methylene}-2-pyrazinecarboxamide.
Claim 11
Dependent Claim
36 words
A compound of claim 2 wherein R 1 , r 2 , r 3 , r 4 , r 5 and R 7 are all hydrogen; and R 6 is isopropyl; which is 3,5-diamino-6-chloro-N-{[(isopropylaminocarbonyl)-amino]aminomethylene}-2-pyrazinecarboxamide hydrochloride monohydrate.
Claim 12
Dependent Claim
33 words
A compound of claim 2 wherein R 1 , r 3 , r 4 , r 5 and R 7 are hydrogen; and R 2 and R 6 are isopropyl; which is 3-amino-5-isoproylamino-6-chloro-N-{(isopropylaminocarbonyl)amino]aminomethylene}-2-pyrazinecarboxamide.
Claim 13
Dependent Claim
34 words
A compound of claim 2 wherein R 1 , r 2 , r 3 , r 4 , r 5 and R 7 are hydrogen; and R 6 is tert-butyl: which is 3,5-diamino-N-{[tert-butylaminocarbonyl)amino]-aminomethylene}-6-chloro-2-pyrazinecarboxamide hemihydrate.
Claim 14
Dependent Claim
35 words
A compound of claim 2 wherein R 1 , r 3 , r 4 , r 5 and R 7 are hydrogen; R 2 is isopropyl; and R 6 is ethyl; which is 3l -amino-5-isopropylamino-6-chloro-N-{[(ethylaminocarbonyl)amino]aminomethylene}-2-pyrazinecarboxamide.
Claim 15
Independent Claim
273 words
A method of treating edema and/or hypertension which comprises administering to a patient a pharmacologically acceptable does of a compound of the formula: ##STR9## wherein R 1 is hydrogen, lower alkyl having from 1 to 5 carbon atoms cycloalkyl having from 3 to 6 carbon atoms, lower alkenyl having from 2 to 3 carbon atoms; R 2 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 1 and R 2 are joined to form with the nitrogen atom to which they are attached a pyrrolidine or piperazine ring; R 3 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 4 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 5 is hydrogen, lower alkyl having 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; phenyl or substituted phenyl wherein the substituent is lower alkyl or halo; benzyl or phenethyl; trifluoroethyl, lower alkylamino, diloweralkylamino, allyl, propargyl, pyridyl, furfuryl, methoxy or hydroxy ethyl; ethoxy carbonyl methyl or carboxy methyl; R 6 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 10 nuclear carbon atoms; R 5 and R 6 are joined to form a piperazine or morpholine ring with the nitrogen atom to which they are attached; R 7 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 3 and R 7 are joined to form an alkylene bridge of 2 carbon atoms; X is halogen; and the pharmaceutically acceptable non-toxic acid addition salts thereof.
Claim 16
Independent Claim
273 words
A method of treating edema and/or hypertension which comprises administering to a patient a pharmacologically acceptable does of a compound of the formula: ##STR9## wherein R 1 is hydrogen, lower alkyl having from 1 to 5 carbon atoms cycloalkyl having from 3 to 6 carbon atoms, lower alkenyl having from 2 to 3 carbon atoms; R 2 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 1 and R 2 are joined to form with the nitrogen atom to which they are attached a pyrrolidine or piperazine ring; R 3 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 4 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 5 is hydrogen, lower alkyl having 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; phenyl or substituted phenyl wherein the substituent is lower alkyl or halo; benzyl or phenethyl; trifluoroethyl, lower alkylamino, diloweralkylamino, allyl, propargyl, pyridyl, furfuryl, methoxy or hydroxy ethyl; ethoxy carbonyl methyl or carboxy methyl; R 6 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 10 nuclear carbon atoms; R 5 and R 6 are joined to form a piperazine or morpholine ring with the nitrogen atom to which they are attached; R 7 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 3 and R 7 are joined to form an alkylene bridge of 2 carbon atoms; X is halogen; and the pharmaceutically acceptable non-toxic acid addition salts thereof.
Claim 17
Independent Claim
105 words
A method of treating edema and hypertension which consists essentially of administering to a patient in need of such treatment a unit dosage of from 5 mg. to 1 gm./day of a compound of the formula: ##STR10## wherein R 1 is hydrogen; R 2 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 3 is hydrogen; R 4 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 5 is hydrogen; R 6 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 7 is hydrogen; and the pharmaceutically acceptable non-toxic and addition salts thereof.
Claim 18
Independent Claim
105 words
A method of treating edema and hypertension which consists essentially of administering to a patient in need of such treatment a unit dosage of from 5 mg. to 1 gm./day of a compound of the formula: ##STR10## wherein R 1 is hydrogen; R 2 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 3 is hydrogen; R 4 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 5 is hydrogen; R 6 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 7 is hydrogen; and the pharmaceutically acceptable non-toxic and addition salts thereof.
Claim 19
Dependent Claim
18 words
A method of treatment according to claim 14 wherein the compound to be administered is 3.5-diamino-6-chloro-N-{[(isopropylaminocarbonyl)amino]aminomethylene}-2-pyrazinecarboxamide hydrochloride monohydrate.
Claim 20
Dependent Claim
16 words
A method of treatment according to claim 14 wherein the compound to be administered is 3-amino-5-isopropylamino-6-chloro-N-{[(ethylaminocarbonyl)amino]-aminomethylene}-2-pyrazinecarboxamide.
Claim 21
Dependent Claim
265 words
A pharmaceutical composition consisting essentially of an active ingredient of a compound of the formula: ##STR11## wherein R 1 is hydrogen, lower alkyl having from 1 to 5 carbon atoms cycloalkyl having from 3 to 6 carbon atoms, lower alkenyl having from 2 to 3 carbon atoms; R 2 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 1 and R 2 are joined to form with the nitrogen atom to which they are attached a pyrrolidine or piperazine ring; R 3 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 4 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 5 is hydrogen, lower alkyl having 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; phenyl or substituted phenyl wherein the substituent is lower alkyl or halo; benzyl or phenethyl; trifluoroethyl, lower alkylamino, diloweralkylamino, allyl, propargyl, pyridyl, furfuryl, methoxy or hydroxy ethyl; ethoxy carbonyl methyl or carboxy methyl; R 6 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 10 nuclear carbon atoms; R 5 and R 6 are joined to form a piperazine or morpholine ring with the nitrogen atom to which they are attached; R 7 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 3 and R 7 are joined to form an alkylene bridge of 2 carbon atoms; X is halogen; and the pharmaceutically acceptable non-toxic acid addition salts thereof.
Claim 22
Dependent Claim
265 words
A pharmaceutical composition consisting essentially of an active ingredient of a compound of the formula: ##STR11## wherein R 1 is hydrogen, lower alkyl having from 1 to 5 carbon atoms cycloalkyl having from 3 to 6 carbon atoms, lower alkenyl having from 2 to 3 carbon atoms; R 2 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 1 and R 2 are joined to form with the nitrogen atom to which they are attached a pyrrolidine or piperazine ring; R 3 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 4 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; R 5 is hydrogen, lower alkyl having 1 to 5 carbon atoms; cycloalkyl having from 3 to 6 nuclear carbon atoms; phenyl or substituted phenyl wherein the substituent is lower alkyl or halo; benzyl or phenethyl; trifluoroethyl, lower alkylamino, diloweralkylamino, allyl, propargyl, pyridyl, furfuryl, methoxy or hydroxy ethyl; ethoxy carbonyl methyl or carboxy methyl; R 6 is hydrogen, lower alkyl having from 1 to 5 carbon atoms; cycloalkyl having from 3 to 10 nuclear carbon atoms; R 5 and R 6 are joined to form a piperazine or morpholine ring with the nitrogen atom to which they are attached; R 7 is hydrogen, lower alkyl having 1 to 5 carbon atoms; R 3 and R 7 are joined to form an alkylene bridge of 2 carbon atoms; X is halogen; and the pharmaceutically acceptable non-toxic acid addition salts thereof.
Claim 23
Dependent Claim
89 words
A pharmaceutical composition consisting essentially of an active ingredient of a compound of the formula: ##STR12## wherein R 1 is hydrogen; R 2 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 3 is hydrogen; R 4 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 5 is hydrogen; R 6 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 7 is hydrogen, and the pharmaceutically acceptable non-toxic acid addition salts thereof and a pharmaceutically acceptable carrier.
Claim 24
Dependent Claim
89 words
A pharmaceutical composition consisting essentially of an active ingredient of a compound of the formula: ##STR12## wherein R 1 is hydrogen; R 2 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 3 is hydrogen; R 4 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 5 is hydrogen; R 6 is hydrogen or lower alkyl having from 1 to 3 carbon atoms; R 7 is hydrogen, and the pharmaceutically acceptable non-toxic acid addition salts thereof and a pharmaceutically acceptable carrier.
Claim 25
Dependent Claim
16 words
A pharmaceutical composition according to claim 18 wherein the active ingredient is 3,5-diamino-6-chloro-N [(isopropylaminocarbonyl)amino]aminomethylene-2-pyrazinecarboxamide hydrochloride monohydrate.
Claim 26
Dependent Claim
13 words
A pharmaceutical composition according to claim 18 wherein the active ingredient is 3-amino-5-isopropylamino-6-chloro-N-{[(ethylaminocarbonyl)amino]-aminomethylene}-2-pyrazinecarboxamide.
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) | 1981-04-17 | 1981-10-17 | 1982-04-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-04-17 | 1985-10-17 | 1986-04-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-04-17 | 1989-10-17 | 1990-04-18 | $7700.00 | Window Closed / Lapsed |