IP Library › Granted Patent US 9,061,998
Granted Patent B2
US 9,061,998 · App. 14/003,423 · Granted Jun 23, 2015

Quinolinone derivatives

Inventors: Alain Claude-Marie Daugan (Les Ulis, FR); Olivier Mirguet (Les Ulis, FR); Yann Lamotte (Les Ulis, FR)
Assignee: GlaxoSmithKline LLC
C07D215/22C07D215/36C07D401/04C07D401/10C07D401/14C07D409/14C07D413/04C07D413/14C07D417/04C07D417/10C07D417/14C07D215/48C07D401/12C07D309/14
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Quick Facts
Patent No.
US 9,061,998
App. No.
14/003,423
Granted
Jun 23, 2015
Kind
B2
Abstract

The present invention relates to compounds of the formula (I), salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds as activators of AMPK.

Claims (237)

1. A compound of formula (I) or a salt thereof:

wherein:

R 1 is a) a 5-membered heteroaryl optionally substituted with 1, 2, or 3 groups independently selected from —CH 3 , —OCH 3 , —OH, —CH 2 OH, —CF 3 , —OCF 3 , —CN, —CO 2 H, —CH 2 CO 2 H, —CONH 2 , —NH 2 and halogen;

b) O-phenyl optionally substituted with a group selected from methyl, methoxy, fluoro, and CO 2 H;

c) selected from the group consisting of H, CO 2 H, CO 2 Et, and NO 2 ;

d) phenyl optionally substituted with a group selected from CO 2 H, Cl, F, methyl, —CN, -NMe 2 and methoxy;

e) selected from the group consisting of 3-pyridinyl, 4-pyridinyl, and —S(O) n -phenyl; or

f) selected from the group consisting of O-pyridin-2-yl, O-(4-methyl-pyridin-2-yl), O-(5-methoxy-pyridin-2-yl) and O-(5-methyl-pyridin-2-yl);

n=0 or 2;

R 2 is H;

R 3 is

R 4 is Cl;

R 5 is H; and

R 7 is H and R 6 is selected from a group consisting of, —NHMe, —NMe 2 , —NHC(O)OMe, —OMe, —OEt, Et, iPr, —CH 2 OH, and —CH 2 CH 2 OH or is a group selected from

or

R 6 and R 7 taken together form a group selected from

or

wherein:

i) R 1 =3-methoxyphenyl, R 4 is F and R 3 =4-(4-morpholino)phenyl;

ii) R 1 =3-methylisoxazol-5-yl, and R 3 =3-dimethylaminophenyl; or

iii) R 1 =3-methoxyphenyl, and R 3 =3-dimethylaminophenyl.

2. The compound or salt thereof according to claim 1 wherein R 1 represents 5-membered heteroaryl optionally substituted by a group selected from —CH 3 , —OCH 3 , —OH, —CH 2 OH, —CF 3 , —OCF 3 , —CN, —CO 2 H, —CH 2 CO 2 H, —CONH 2 , —NH 2 and halogen.

3. The compound or salt thereof according to claim 1 wherein R 1 represents 5-membered heteroaryl optionally substituted with 1, 2, or 3 groups independently selected from methyl, chloro, bromo, CO 2 H and methoxy.

4. The compound or salt thereof according to claim 1 wherein R 3 represents

5. The compound or salt thereof according to claim 1 wherein R 3 represents

6. A compound of formula (A) or a salt thereof:

wherein

R 1 represents 5-membered heteroaryl optionally substituted by —CH 3 , —OCH 3 , —OH, —CH 2 OH, —CF 3 , —OCF 3 , —CN, —CO 2 H, —CH 2 CO 2 H, —CONH 2 , —NH 2 or halogen;

R 2 represents H;

R 3 is

R 4 represents chloro;

R 5 represents H; and

R 7 is H and R 6 is selected from a group consisting of —NHMe, —NMe 2 , —NHC(O)OMe, Et, and iPr, or is a group selected from

7. The compound or salt thereof according to claim 1 , selected from the group consisting of:

7-Chloro-4-hydroxy-6-(2′-hydroxy-3′-methoxy-[1,1′-biphenyl]-4-yl)-3-phenylquinolin-2(1H)-one;

3-{7-Chloro-4-hydroxy-6-[2′-hydroxy-3′-(methyloxy)-4-biphenylyl]-2-oxo-1,2-dihydro-3-quinolinyl}benzoic acid;

7-chloro-4-hydroxy-3-(3-methoxyphenyl)-6-(4-morpholinophenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-[4-(4-morpholinyl)phenyl]-3-phenylquinolin-2(1H)-one;

4-{7-Chloro-4-hydroxy-3-[3-(methyloxy)phenyl]-2-oxo-1,2-dihydro-6-quinolinyl}-N-cyclopentylbenzamide;

7-Fluoro-4-hydroxy-3-(3-methoxyphenyl)-6-(4-morpholinophenyl)quinolin-2(1H)-one;

3-[7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-2-oxo-1,2-dihydro-3-quinolinyl]benzoic acid;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-[3-(methyloxy)phenyl]quinolin-2(1H)-one;

N-{4-[4-(7-Chloro-4-hydroxy-2-oxo-3-phenyl-1,2-dihydro-6-quinolinyl)phenyl]-1,3-thiazol-2-yl}acetamide;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-phenylquinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methylisoxazol-5-yl)-6-(4-(piperidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(1-methyl-1H-pyrazol-4-yl)-6-(4-(piperidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-6-(4′-fluoro-[1,1′-biphenyl]-4-yl)-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(3′-methoxy-[1,1′-biphenyl]-4-yl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methylisoxazol-5-yl)-6-(4-(5-methylthiophen-2-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4′-methoxy-[1,1′-biphenyl]-4-yl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-6-(2′-fluoro-[1,1′-biphenyl]-4-yl)-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

3-(7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)benzonitrile;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(3-methyl-1,2,4-oxadiazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-3,6-bis(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-3-(4-cyanophenyl)-6-(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(5-methyl-1,3,4-oxadiazol-2-yl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(2-methylthiazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(2,4-dimethylthiazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-3-(5-methyl-1,3,4-oxadiazol-2-yl)-2-oxo-6-(4-(piperidin-1-yl)phenyl)-1,2-dihydroquinolin-4-olate;

Ethyl 7-chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-2-oxo-1,2-dihydro-3-quinolinecarboxylate;

Ethyl 7-chloro-4-hydroxy-6-[2′-hydroxy-3′-(methyloxy)-4-biphenylyl]-2-oxo-1,2-dihydro-3-quinoline carboxylate;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-nitroquinolin-2(1H)-one;

Ethyl 7-chloro-4-hydroxy-6-[4-(4-morpholinyl)phenyl]-2-oxo-1,2-dihydro-3-quinolinecarboxylate;

7-Chloro-4-hydroxy-3-(3-methylisoxazol-5-yl)-6-(4-morpholino phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methoxyphenyl)-6-(4-(piperidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methoxyphenyl)-6-(1-methyl-1H-benzo [d]imidazol-6-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methoxyphenyl)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

Methyl (4-(7-chloro-4-hydroxy-3-(3-methoxyphenyl)-2-oxo-1,2-dihydroquinolin-6-yl)phenyl) carbamate;

7-Chloro-6-[4-(dimethylamino)phenyl]-4-hydroxy-3-[3-(methyloxy)phenyl]quinolin-2(1H)-one;

7-Chloro-6-(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-3-(3-methoxyphenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methoxyphenyl)-6-(4-(4-methylpiperazin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-6-(4-ethylphenyl)-4-hydroxy-3-(3-methoxyphenyl)quinolin-2(1H)-one;

7-Chloro-6-[3-(dimethylamino) phenyl]-4-hydroxy-3-[3-(methyloxy)phenyl]-2(1H)-quinolinone;

7-Chloro-6-(3-(dimethylamino)phenyl)-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-ethylphenyl)-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(2′-hydroxy-3′-methoxy-[1,1′-biphenyl]-4-yl)-3-(3-methylisoxazol-5-yl) quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-morpholinophenyl)-3-phenoxyquinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-phenylquinolin-2(1H)-one;

6-(4-(1H-Pyrazol-1-yl)phenyl)-7-chloro-4-hydroxy-3-phenylquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-methoxyphenyl)-3-phenylquinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-morpholinophenyl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-phenoxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-phenyl-6-(4-(piperidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(2-hydroxyethyl)phenyl)-3-phenylquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(3-hydroxypiperidin-1-yl)phenyl)-3-(3-methoxyphenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(2′-hydroxy-3′-methoxy-[1,1′-biphenyl]-4-yl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methoxyphenyl)-6-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-phenyl-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(2′-hydroxy-3′-methoxy-[1,1′-biphenyl]-4-yl)-3-phenoxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(2′-hydroxy-3′-methoxy-[1,1′-biphenyl]-4-yl)quinolin-2(1H)-one;

N-(4-(4-(7-Chloro-4-hydroxy-2-oxo-3-phenoxy-1,2-dihydroquinolin-6-yl)phenyl)thiazol-2-yl) acetamide;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(o-tolyloxy)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(4-methoxyphenoxyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(hydroxymethyl)phenyl)-3-phenylquinolin-2(1H)-one;

7-Chloro-3-(3-fluorophenoxy)-4-hydroxy-6-(4-isopropylphenyl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(3-fluorophenoxy)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(methylamino)phenyl)-3-phenylquinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(1H-pyrazol-1-yl)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-6-(4-ethoxyphenyl)-4-hydroxy-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-phenoxy-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-6-(4-ethylphenyl)-4-hydroxy-3-phenoxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-isopropylphenyl)-3-phenoxyquinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(3-methoxyphenoxyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methoxyphenoxy)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-isopropylphenyl)-3-(3-methoxyphenoxyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(cyclopropylmethoxy)phenyl)-4-hydroxy-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3-(1H-pyrazol-1-yl) quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indazol-5-yl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-isopropylphenyl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-3-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(4-(dimethylamino)phenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(p-tolyloxy)quinolin-2(1H)-one;

7-Chloro-6-(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(4-methyl-1,2,5-oxadiazol-3-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(pyridin-4-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(pyridin-2-yloxy)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(1H-1,2,4-triazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(2-methoxyphenoxyl)quinolin-2 (1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(1H-1,2,3-triazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(4-methyl-1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(m-tolyloxy)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(pyridin-3-yl)quinolin-2(1H)-one;

3-((7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)oxy) benzoic acid;

1-(7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-1H-pyrazole-4-carboxylic acid;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(4-fluorophenoxy)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(2′-hydroxy-[1, 1′-biphenyl]-4-yl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-3-(1,3-dimethyl-1H-pyrazol-5-yl)-6-(4-(dimethylamino)phenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(piperidin-1-yl)phenyl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-((4-methylpyridin-2-yl)oxy)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methylisoxazol-5-yl)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-methoxyphenyl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(pyridin-3-yl)quinolin-2(1H)-one;

1-(7-Chloro-4-hydroxy-2-oxo-6-(4-(pyrrolidin-1-yl)phenyl)-1,2-dihydroquinolin-3-yl)-1H-pyrazole-4-carboxylic acid;

7-Chloro-4-hydroxy-3-(pyridin-3-yl)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(4-methyl-1,2,5-oxadiazol-3-yl)-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(4-methyl-1,2,5-oxadiazol-3-yl)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2 (1H)-one;

7-Chloro-4-hydroxy-3-(pyridin-4-yl)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(4-methyl-1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(pyridin-4-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-phenoxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(2-methoxyphenoxy)-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(p-tolyloxy)quinolin-2(1H)-one;

7-Chloro-3-(3-fluorophenoxy)-4-hydroxy-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

6-([1,1′-Biphenyl]-4-yl)-7-chloro-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-cyclohexylphenyl)-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(5-methyl-1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(5-methyl-1H-pyrazol-1-yl)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2 (1H)-one;

7-Chloro-4-hydroxy-3-(3-methylisoxazol-5-yl)-6-(naphthalen-2-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(3-hydroxypiperidin-1-yl)phenyl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(phenylthio)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-morpholinophenyl)-3-(phenylthio)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(hydroxymethyl)phenyl)-3-(phenylthio)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(6-methoxynaphthalen-2-yl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-methoxyphenyl)-3-phenoxyquinolin-2(1H)-one;

6-(4-(1H-Pyrazol-1-yl)phenyl)-7-chloro-4-hydroxy-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1H-indol-5-yl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-3-(1,3-dimethyl-1H-pyrazol-5-yl)-4-hydroxy-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

7-Chloro-3-(4-chloro-1H-pyrazol-1-yl)-6-(4-(dimethylamino)phenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(3-methoxyphenoxy)-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

7-Chloro-3-(1,3-dimethyl-1H-pyrazol-5-yl)-4-hydroxy-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(1H-1,2,4-triazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(1-methyl-1H-pyrazol-4-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-((5-methylpyridin-2-yl)oxy)quinolin-2(1H)-one;

7-Chloro-3-(4-chloro-1H-pyrazol-1-yl)-4-hydroxy-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(pyrrolidin-1-yl)phenyl)-3-(1H-1,2,4-triazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(piperidin-1-yl)phenyl)-3-(1H-1,2,4-triazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(3-fluorophenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(methylamino)phenyl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(4-methyl-1H-pyrazol-1-yl)-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(4-methyl-1H-pyrazol-1-yl)-6-(4-(piperidin-1-yl)phenyl)quinolin-2 (1H)-one;

7-Chloro-4-hydroxy-6-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(1-ethyl-1H-indol-5-yl)-4-hydroxy-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(4-methyl-1,2,5-oxadiazol-3-yl)-6-(4-(piperidin-1-yl)phenyl)quinolin-2 (1H)-one;

7-Chloro-4-hydroxy-6-(4-(piperidin-1-yl)phenyl)-3-(pyridin-3-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-nitroquinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(phenylsulfonyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)-3-(phenylsulfonyl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(4-fluorophenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(o-tolyl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(2-methoxyphenyl)quinolin-2(1H)-one;

7-Chloro-3-(4-chlorophenyl)-6-(4-(dimethylamino)phenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-3-(3-chlorophenyl)-6-(4-(dimethylamino)phenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-3-(2-chlorophenyl)-6-(4-(dimethylamino)phenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-3-(2-fluoro phenyl)-4-hydroxyquinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-6-yl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methylindolin-5-yl)-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(4-methoxy-1H-pyrazol-1-yl)-6-(4-(piperidin-1-yl)phenyl)quinolin-2 (1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(m-tolyl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(p-tolyl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-3-(2-methoxyphenoxy) quinolin-2(1H)-one;

7-chloro-4-hydroxy-6-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-3-(4-methoxy-1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(1-(hydroxymethyl)cyclopentyl)phenyl)-3-(3-methylisoxazol-5-yl) quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(4-methoxyphenyl) quinolin-2(1H)-one;

Methyl 1-(4-(7-chloro-4-hydroxy-3-(3-methylisoxazol-5-yl)-2-oxo-1,2-dihydroquinolin-6-yl)phenyl)cyclopropane carboxylate;

7-Chloro-3-(3-chlorophenyl)-4-hydroxy-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

7-Chloro-3-(3-chlorophenyl)-4-hydroxy-6-(4-(pyrrolidin-1-yl)phenyl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(4-methoxy-1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(1-(hydroxymethyl)cyclobutyl)phenyl)-3-(3-methylisoxazol-5-yl) quinolin-2(1H)-one;

7-Chloro-6-(4-(1-hydroxycyclobutyl)phenyl)-3-(3-methylisoxazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-6-(1-ethyl-1H-indol-5-yl)-3-(3-methylisoxazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-6-(4-ethoxyphenyl)-3-(3-methylisoxazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-6-(4-(3-hydroxyoxetan-3-yl)phenyl)-3-(3-methylisoxazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-olate;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(3-methyl-1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-((4-methoxypyridin-2-yl)oxy)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-3-(4-methoxyphenoxy)-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

7-Chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-((5-methylpyridin-2-yl)oxy)quinolin-2(1H)-one;

7-Chloro-6-(2′-fluoro-[1,1′-biphenyl]-4-yl)-4-hydroxy-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(4-(5-methylthiophen-2-yl)phenyl)-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one;

3-(4-Bromo-1H-pyrazol-1-yl)-7-chloro-6-(4-(dimethylamino)phenyl)-4-hydroxyquinolin-2(1H)-one;

3-(4-Bromo-1H-pyrazol-1-yl)-7-chloro-4-hydroxy-6-(4-(piperidin-1-yl)phenyl)quinolin-2 (1H)-one;

6-[4-(2-Amino-1,3-thiazol-4-yl)phenyl]-7-chloro-4-hydroxy-3-phenylquinolin-2(1H)-one;

6-[4-(2-Amino-1,3-thiazol-4-yl)phenyl]-7-chloro-4-hydroxy-3-[3-(methyloxy)phenyl]quinolin-2(1H)-one;

6-(4-(2-Amino-1,3-thiazol-4-yl)phenyl)-7-chloro-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one;

6-(4-(2-Amino-1,3-thiazol-4-yl)phenyl)-7-chloro-4-hydroxy-3-(3-methoxyphenyl)quinolin-2(1H)-one;

6-(4-(2-Amino-1,3-thiazol-4-yl)phenyl)-7-chloro-4-hydroxy-3-(pyridin-3-yl)quinolin-2(1H)-one;

6-[4-(2-Amino-1,3-thiazol-4-yl)phenyl]-7-chloro-4-hydroxy-3-(1H-pyrazol-1-yl)-2(1H)-quinolinone;

6-(4-(2-Amino-1,3-thiazol-4-yl)phenyl)-7-chloro-4-hydroxy-3-(pyridin-4-yl)quinolin-2(1H)-one;

6-(4-(2-Amino-1,3-thiazol-4-yl)phenyl)-7-chloro-4-hydroxy-3-(4-methyl-1H-pyrazol-1-yl) quinolin-2(1H)-one;

6-(4-(2-Amino-1,3-thiazol-4-yl)phenyl)-7-chloro-4-hydroxy-3-(1H-1,2,3-triazol-1-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-(1-methyl-1H-indol-5-yl)quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-[4-(4-morpholinyl)phenyl]quinolin-2(1H)-one;

7-Chloro-4-hydroxy-6-[2′-hydroxy-3′-(methyloxy)-4-biphenylyl]-2-oxo-1,2-dihydro-3-quinolinecarboxylic acid;

1-(4-(7-Chloro-3-(3-methylisoxazol-5-yl)-4-oxido-2-oxo-1,2-dihydroquinolin-6-yl)phenyl)cyclopropanecarboxylate;

1-(7-Chloro-4-oxido-2-oxo-6-(4-(piperidin-1-yl)phenyl)-1,2-dihydroquinolin-3-yl)-1H-pyrazole-4-carboxylate; and

7-Chloro-3-(3-chlorophenyl)-4-hydroxy-6-(4-(piperidin-1-yl)phenyl) quinolin-2(1H)-one;

or a pharmaceutically acceptable salt thereof.

8. The compound or salt thereof according to claim 1 wherein the salt is a pharmaceutically acceptable salt.

9. A compound which is 7-chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one, represented by the formula:

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 9 which is 7-chloro-6-(4-(dimethylamino)phenyl)-4-hydroxy-3-(3-methylisoxazol-5-yl)quinolin-2(1H)-one, represented by the formula:

11. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 8 and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 9 and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising the compound according to claim 10 and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 17, 2014
From: DAUGAN, ALAIN CLAUDE-MARIE; LAMOTTE, YANN; MIRGUET, OLIVIER
To: GLAXOSMITHKLINE LLC
Reel/Frame 032230/0271 →
Continuity (2)
Provisional Application 61449853 · Mar 7, 2011
Related Publication 20130345212A1 · Dec 26, 2013