IP Library › Granted Patent US 12668582
Granted Patent B2
US 12668582 · App. 18/598,312 · Granted Jun 30, 2026

Phosphodiesterase 3 (PDE3) inhibitors

Inventors: Richard A. Ewin (Kalamazoo, MI); Michael P. Curtis (Kalamazoo, MI); Todd M. Maddux (Kalamazoo, MI); Graham M. Kyne (Kalamazoo, MI)
Assignee: Zoetis Services LLC
C07D401/04A61K31/433A61K31/437A61K31/4375A61K31/501A61K31/506A61K31/549A61K31/55A61K45/06C07D401/14C07D403/04C07D417/04C07D417/14C07D471/04
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Quick Facts
Patent No.
US 12668582
App. No.
18/598,312
Granted
Jun 30, 2026
Kind
B2
Abstract

The invention describes novel PDE3 inhibitors for treating a cardiovascular disease including myxomatous mitral valve disease, congestive heart failure and/or asymptomatic heart failure in animals, particularly canines.

Claims (206)

1 . A compound selected from the group consisting of:

8-(2-methoxypyridin-4-yl)-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-8-(thiazol-2-yl)-3,4-dihydroquinolin-2(1H)-one;

8-(2-methoxythiazol-5-yl)-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

7-chloro-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-(4-chlorophenyl)-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

7′-chloro-5′-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)spiro[cyclopropane-1,3′-indolin]-2′-one;

8-(4-chlorophenyl)-6-(6-oxo-1,6-dihydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

8-(3-fluorophenyl)-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-8-(pyridin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

3,3-dimethyl-5-(4-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-7-(thiazol-4-yl) indolin-2-one;

9-(6-methoxypyridin-3-yl)-7-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one;

6-(2-(1-(4-methoxyphenyl)cyclopropyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-chloro-3,3-dimethyl-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

7-fluoro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-fluoro-3,3-dimethyl-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

7′-fluoro-5′-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)spiro[cyclopropane-1,3′-indolin]-2′-one;

7-chloro-3,3-dimethyl-5-(6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

4-chloro-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)benzo[d]thiazol-2 (3H)-one;

6-(2-amino-4-chlorobenzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(2-amino-4-fluorobenzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

(R)-7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

6-(4-fluoro-2-(methylamino)benzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(8-chloro-2-hydroxyquinolin-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-chloro-6-fluoro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

6-(4-fluoro-2-(3-hydroxyazetidin-1-yl)benzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

2-amino-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)benzo[d]thiazole-4-carbonitrile;

7-chloro-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) isoindolin-1-one;

2-hydroxy-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) quinoline-8-carbonitrile;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) isoindolin-1-one;

4-chloro-1-methyl-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one;

7′-fluoro-5′-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)spiro[cyclobutane-1,3′-indolin]-2′-one;

6-(8-bromo-2-hydroxyquinolin-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(4-fluoro-2-(((1-methyl-1H-pyrazol-4-yl)methyl)amino)benzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(7-chloro-3-methyl-1H-indazol-5-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(8-cyclopropyl-2-hydroxyquinolin-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(2-(3-methoxyazetidin-1-yl)benzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-fluoro-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

(S)-7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) isoindolin-2-one;

4-chloro-6-(6-oxo-1,6-dihydropyridazin-3-yl)benzo[d]thiazol-2 (3H)-one;

5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-2-oxoindoline-7-carbonitrile;

4-methyl-6-(6-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)benzo[d]thiazol-2 (3H)-one;

4-chloro-6-(6-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)benzo[d]thiazol-2 (3H)-one;

5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7′-chloro-2′-oxospiro[cyclopropane-1,3′-indolin]-5′-yl)-6-methyl-3,6-dihydro-2H-1, 3,4-thiadiazin-2-one;

5-(7-fluoro-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(7-(4-(methylsulfonyl)phenyl)-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(3,3-dimethyl-2-oxo-7-(thiazol-4-yl) indolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-(4-chlorophenyl)-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(9-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-fluoro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(6-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)-2-oxoindoline-7-carbonitrile;

(S)-5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-1-oxoisoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-1-oxoisoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(8-chloro-2-hydroxyquinolin-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-2,2-dioxido-1,3-dihydrobenzo[c]isothiazol-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(8-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

4-chloro-6-(2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)benzo[d]oxazol-2 (3H)-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one;

7-chloro-3,3-dimethyl-5-(pyrimidin-5-yl) indolin-2-one;

6-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one;

4-chloro-6-(5-oxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)benzo[d]thiazol-2 (3H)-one; and

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-1,3,4-thiadiazol-2 (3H)-one, stereoisomers thereof, and veterinarily acceptable salts thereof.

2 . The compound of claim 1 selected form the group consisting of:

8-(2-methoxypyridin-4-yl)-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

8-(2-methoxythiazol-5-yl)-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

7-chloro-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7′-chloro-5′-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)spiro[cyclopropane-1,3′-indolin]-2′-one;

8-(4-chlorophenyl)-6-(6-oxo-1,6-dihydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

8-(3-fluorophenyl)-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-8-(pyridin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

9-(6-methoxypyridin-3-yl)-7-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one;

6-(2-(1-(4-methoxyphenyl)cyclopropyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-chloro-3,3-dimethyl-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

7-fluoro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-fluoro-3,3-dimethyl-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

7′-fluoro-5′-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)spiro[cyclopropane-1,3′-indolin]-2′-one;

7-chloro-3,3-dimethyl-5-(6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

6-(2-amino-4-chlorobenzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(2-amino-4-fluorobenzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

(R)-7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

6-(4-fluoro-2-(methylamino)benzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(8-chloro-2-hydroxyquinolin-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-chloro-6-fluoro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

6-(4-fluoro-2-(3-hydroxyazetidin-1-yl)benzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

2-amino-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)benzo[d]thiazole-4-carbonitrile;

7-chloro-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) isoindolin-1-one;

2-hydroxy-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) quinoline-8-carbonitrile;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) isoindolin-1-one;

4-chloro-1-methyl-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one;

7′-fluoro-5′-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)spiro[cyclobutane-1,3′-indolin]-2′-one;

4-chloro-6-(6-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)benzo[d]thiazol-2 (3H)-one;

5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7′-chloro-2′-oxospiro[cyclopropane-1,3′-indolin]-5′-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-fluoro-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(7-(4-(methylsulfonyl)phenyl)-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-(4-chlorophenyl)-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(9-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-fluoro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(6-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)-2-oxoindoline-7-carbonitrile;

(S)-5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-1-oxoisoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-1-oxoisoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(8-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one; and

7-chloro-3,3-dimethyl-5-(pyrimidin-5-yl) indolin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

3 . The compound of claim 2 selected from the group consisting of:

8-(3-fluorophenyl)-6-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one;

6-(2-(1-(4-methoxyphenyl)cyclopropyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-fluoro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-fluoro-3,3-dimethyl-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

7′-fluoro-5′-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)spiro[cyclopropane-1,3′-indolin]-2′-one;

6-(2-amino-4-chlorobenzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

6-(2-amino-4-fluorobenzo[d]thiazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(6-oxo-1,6-dihydropyridazin-3-yl) indolin-2-one;

(R)-7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

4-chloro-6-(6-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)benzo[d]thiazol-2 (3H)-one;

5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7′-chloro-2′-oxospiro[cyclopropane-1,3′-indolin]-5′-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(9-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-fluoro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(6-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)-2-oxoindoline-7-carbonitrile;

(S)-5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-1, 3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one; and

7-chloro-3,3-dimethyl-5-(pyrimidin-5-yl) indolin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

4 . The compound of claim 3 that is a compound selected from the group consisting of:

6-(2-(1-(4-methoxyphenyl)cyclopropyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(9-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-fluoro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one; and

7-chloro-3,3-dimethyl-5-(pyrimidin-5-yl)indolin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

5 . The compound of claim 4 that is selected from the group consisting of

6-(2-(1-(4-methoxyphenyl)cyclopropyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one; and

6-methyl-5-(9-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

6 . The compound of claim 4 that is selected from the group consisting of

7-bromo-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

5-(7-fluoro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one; and

7-chloro-3,3-dimethyl-5-(pyrimidin-5-yl)indolin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

7 . The compound of claim 4 that is selected from the group consisting of

6-(2-(1-(4-methoxyphenyl)cyclopropyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)indolin-2-one;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)indolin-2-one;

5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one; and

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

8 . The compound of claim 7 that is 6-(2-(1-(4-methoxyphenyl)cyclopropyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, stereoisomers thereof, and veterinary acceptable salts thereof.

9 . The compound of claim 7 that is 7-bromo-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

10 . The compound of claim 7 that is 7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

11 . The compound of claim 7 that is 5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one; stereoisomers thereof, and veterinary acceptable salts thereof.

12 . The compound of claim 7 that is 5-(7-chloro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one; and stereoisomers thereof, and veterinary acceptable salts thereof.

13 . The compound of claim 7 that is 5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

14 . A composition comprising a compound of claim 1 , stereoisomer thereof, or a veterinary acceptable salt thereof.

15 . The composition of claim 14 , wherein the compound is selected from the group selected from

6-(2-(1-(4-methoxyphenyl)cyclopropyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one;

7-bromo-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

7-chloro-3,3-dimethyl-5-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) indolin-2-one;

5-(7-fluoro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

6-methyl-5-(9-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-fluoro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-chloro-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one;

5-(7-bromo-3,3-dimethyl-2-oxoindolin-5-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one; and

7-chloro-3,3-dimethyl-5-(pyrimidin-5-yl) indolin-2-one, stereoisomers thereof, and veterinary acceptable salts thereof.

16 . The composition of claim 14 , further comprising a veterinary acceptable excipient.

17 . The composition of claim 16 , wherein the composition is administered orally.

18 . The composition of claim 14 , wherein the composition further comprises an additional pharmaceutical agent selected from the group consisting of an ACE inhibitor, furosemide or a spironolactone.

19 . A method of treating an animal with myxomatous mitral valve disease, congestive heart failure and/or asymptomatic heart failure, by administering a therapeutic amount of a compound of claim 1 , stereoisomer thereof, or veterinary acceptable salt thereof, to an animal in need thereof.

20 . The method of claim 19 , wherein the animal is co-administered an additional pharmaceutical agent selected from the group consisting of an ACE inhibitor, furosemide or a spironolactone.