US4313951A
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3-Substituted-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones, their cardiotonic use and intermediates therefor
Assignee: Sanofi Aventis US LLC
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Filing: 1980-10-20
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Granted: 1982-02-02
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Expires: 2000-10-20
Abstract
Abstract 1-R 1 -3-[amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino]-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones or pharmaceutically-acceptable acid-addition or cationic salts thereof are useful as cardiotonic agents, where R 1 is hydrogen, lower-alkyl or lower-hydroxyalkyl. 1-R 1 -3-amino-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones are prepared by hydrolyzing the corresponding 3-cyano compounds to produce the corresponding 3-carbamyl compounds and reacting the latter with a reagent capable of converting carbamyl to amino. The 1-R 1 -3-cyano-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones are prepared by reacting (pyridinylmethyl) lower-alkyl ketones with dimethylformamide di-(lower-alkyl) acetal to produce 1-(pyridinyl)-2-(dimethylamino)ethenyl lower-alkyl ketone and reacting said ketones with N-R 1 -α-cyanoacetamide to produce the 1-R 1 -3-cyano-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones. Also shown are the conversions: of the 3-cyano compounds to the 3-H compounds; of the 3-H compounds to the 3-halo compounds; of the 3-halo compounds to the 3-[mono-(lower-alkyl)- or di-(lower-alkyl)-amino]compounds; and, of the 3-amino compounds to the 3-lower-acylamino or 3-[mono-(lower-alkyl)- or di-(lower-alkyl)amino] compounds.
Inventors
- 👤 George Y. Lesher
- 👤 Richard E. Philion
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 20:34
CPC Classifications
C; C07; C07D; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/62; C07D213/63; C07D213/64; C07D213/24; C07D213/44; C07D213/46; C07D213/50; C07D213/72; C07D213/73; C07D213/74; C07D213/75; C07D213/78; C07D213/79; C07D213/80; C07D213/81; C07D213/82; C07D213/84; C07D213/85
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
54 words
A 1-R 1 -3-Q-5-PY-6-R-2(1H)-pyridinone having the formula ##STR3## where Q is amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino, R 1 is hydrogen, lower-alkyl or lower-hydroxyalkyl, R is lower-alkyl and PY is 4-, 3- or 2-pyridinyl or 4-, 3- or 2-pyridinyl having one or two lower-alkyl substituents, or pharmaceutically-acceptable acid-addition or cationic salt thereof.
Claim 2
Dependent Claim
54 words
A 1-R 1 -3-Q-5-PY-6-R-2(1H)-pyridinone having the formula ##STR3## where Q is amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino, R 1 is hydrogen, lower-alkyl or lower-hydroxyalkyl, R is lower-alkyl and PY is 4-, 3- or 2-pyridinyl or 4-, 3- or 2-pyridinyl having one or two lower-alkyl substituents, or pharmaceutically-acceptable acid-addition or cationic salt thereof.
Claim 3
Dependent Claim
10 words
A compound according to claim 1 where Q is amino.
Claim 4
Dependent Claim
10 words
A compound according to claim 1 where Q is cyano.
Claim 5
Dependent Claim
10 words
A compound according to claim 1 where Q is carbamyl.
Claim 6
Dependent Claim
10 words
A compound according to claim 1 where Q is halo.
Claim 7
Dependent Claim
10 words
A compound according to claim 1 where Q is lower-alkylamino.
Claim 8
Dependent Claim
10 words
A compound according to claim 1 where Q is di-(lower-alkyl)amino.
Claim 9
Dependent Claim
10 words
A compound according to claim 1 where Q is lower-acylamino.
Claim 10
Dependent Claim
6 words
3-Amino-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 11
Dependent Claim
6 words
3-Amino-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 12
Dependent Claim
6 words
3-Amino-6-ethyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 13
Dependent Claim
6 words
3-Amino-6-ethyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 14
Dependent Claim
6 words
3-Amino-6-n-propyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 15
Dependent Claim
6 words
3-Amino-6-n-propyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 16
Dependent Claim
6 words
1,2-Dihydro-6-methyl-2-oxo-5-(4-pyridinyl)nicotinonitrile or pharmaceutically-acceptable acid-addition salt thereof.
Claim 17
Dependent Claim
6 words
1,2-Dihydro-6-methyl-2-oxo-5-(4-pyridinyl)nicotinonitrile or pharmaceutically-acceptable acid-addition salt thereof.
Claim 18
Dependent Claim
6 words
6-Methyl-3-methylamino-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 19
Dependent Claim
6 words
6-Methyl-3-methylamino-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 20
Dependent Claim
6 words
3-Bromo-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 21
Dependent Claim
6 words
3-Bromo-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 22
Dependent Claim
5 words
6-Ethyl-1,2-dihydro-2-oxo-5-(4-pyridinyl)nicotinonitrile according to claim 3.
Claim 23
Dependent Claim
5 words
1,2-Dihydro-6-methyl-2-oxo-5-(4-pyridinyl)nicotinamide according to claim 4.
Claim 24
Dependent Claim
5 words
6-Ethyl-1,2-dihydro-2-oxo-5-(4-pyridinyl)nicotinamide according to claim 4.
Claim 25
Dependent Claim
5 words
3-Ethylamino-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone according to claim 6.
Claim 26
Dependent Claim
5 words
3-Dimethylamino-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone according to claim 7.
Claim 27
Dependent Claim
79 words
A cardiotonic composition for increasing cardiac contractility, said composition comprising a pharmaceutically-acceptable inert carrier and, as the active component thereof, an effective amount of a cardiotonic 1-R 1 -3-Q-5-PY-6-R-2(1H)pyridinone having the formula ##STR4## where Q is amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino, R 1 is hydrogen, lower-alkyl or lower-hydroxyalkyl, R is lower-alkyl and PY is 4-, 3- or 2-pyridinyl or 4-, 3- or 2-pyridinyl having one or two lower-alkyl substituents, or pharmaceutically-acceptable acid-addition or cationic salt thereof.
Claim 28
Dependent Claim
79 words
A cardiotonic composition for increasing cardiac contractility, said composition comprising a pharmaceutically-acceptable inert carrier and, as the active component thereof, an effective amount of a cardiotonic 1-R 1 -3-Q-5-PY-6-R-2(1H)pyridinone having the formula ##STR4## where Q is amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino, R 1 is hydrogen, lower-alkyl or lower-hydroxyalkyl, R is lower-alkyl and PY is 4-, 3- or 2-pyridinyl or 4-, 3- or 2-pyridinyl having one or two lower-alkyl substituents, or pharmaceutically-acceptable acid-addition or cationic salt thereof.
Claim 29
Dependent Claim
17 words
A composition according to claim 20 where the active component is 3-amino-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 30
Dependent Claim
17 words
A composition according to claim 20 where the active component is 1,2-dihydro-6-methyl-2-oxo-5-(4-pyridinyl)nicotinonitrile or pharmaceutically-acceptable acid-addition salt thereof.
Claim 31
Dependent Claim
17 words
A composition according to claim 20 where the active component is 3-amino-6-ethyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof.
Claim 32
Independent Claim
87 words
The method for increasing cardiac contractility in a patient requiring such treatment which comprises administering orally or parenterally in a solid or liquid dosage form to such patient an effective amount of a cardiotonic 1-R 1 -3-Q-5-PY-6-R-2(1H)-pyridinone having the formula ##STR5## where Q is amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino, R 1 is hydrogen, lower-alkyl or lower-hydroxyalkyl, R is lower-alkyl and PY is 4-, 3- or 2-pyridinyl or 4-, 3- or 2-pyridinyl having one or two lower-alkyl substitutents, or pharmaceutically-acceptable acid-addition or cationic salt thereof.
Claim 33
Independent Claim
87 words
The method for increasing cardiac contractility in a patient requiring such treatment which comprises administering orally or parenterally in a solid or liquid dosage form to such patient an effective amount of a cardiotonic 1-R 1 -3-Q-5-PY-6-R-2(1H)-pyridinone having the formula ##STR5## where Q is amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino, R 1 is hydrogen, lower-alkyl or lower-hydroxyalkyl, R is lower-alkyl and PY is 4-, 3- or 2-pyridinyl or 4-, 3- or 2-pyridinyl having one or two lower-alkyl substitutents, or pharmaceutically-acceptable acid-addition or cationic salt thereof.
Claim 34
Dependent Claim
19 words
The method according to claim 24 where Q is amino, R is methyl or ethyl, and PY is 4-pyridinyl.
Claim 35
Dependent Claim
19 words
The method according to claim 24 where Q is cyano, R is methyl or ethyl, and PY is 4-pyridinyl.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-02-01 | 1985-08-03 | 1986-02-02 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-02-01 | 1989-08-03 | 1990-02-02 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-02-01 | 1993-08-03 | 1994-02-02 | $7700.00 | Window Closed / Lapsed |