IP Library Granted Patent US 8,426,406
Granted Patent B2
US 8,426,406 · App. 12/992,237 · Granted Apr 23, 2013

Glucocorticoid receptor agonist comprising 2,2,4-trimethyl-6-phenyl-1,2-dihydroquinoline derivatives having substituted oxy group

Inventors: Masatomo Kato (Ikoma, JP); Miwa Takai (Ikoma, JP); Takahiro Matsuyama (Ikoma, JP); Tatsuji Kurose (Ikoma, JP); Yumi Hagiwara (Ikoma, JP); Mamoru Matsuda (Ikoma, JP); Toshiyuki Mori (Ikoma, JP); Kenji Imoto (Ikoma, JP); Atsuyoshi Dota (Ikoma, JP)
Assignee: Santen Pharmaceutical Co., Ltd.
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Quick Facts
Patent No.
US 8,426,406
App. No.
12/992,237
Granted
Apr 23, 2013
Kind
B2
Abstract

The present invention is related to glucocorticoid receptor agonists comprised of a compound represented by formula (1) which is 2,2,4-trimethyl-6-phenyl-1,2-dihydroquinoline derivative or a salt thereof and novel pharmacological effects of the glucocorticoid receptor agonists. In the formula (1), R 1 represents formula (2a), (3a), (4a) or (5a); R2 represents —(CO)—R8, —(CO)O—R9, or the like; R 2 —O— is substituted at the 4- or -5-position of benzene ring A; R 3 represents a lower alkyl group; R 4 , R 5 , R 6 or R 7 represents a halogen atom, a lower alkyl group which may have a substituent, or the like; m, n, p or q represents 0, 1 or the like; R 8 , R 9 or the like represents a lower alkyl group which may have a substituent, a lower alkenyl group, or the like.

Claims (155)

1. A method of treating an inflammatory disease or immune disease, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound represented by formula (1) or a salt thereof:

wherein R 1 represents formula (2a), (3a), (4a) or (5a);

R 2 represents —(CO)—R 8 , —(CO)O—R 9 , —(SO)—R 10 , —(SO 2 )—R 11 or —(CO)NR 12 R 13 ;

R 2 —O— is substituted at the 4- or -5-position of benzene ring A;

R 3 represents a lower alkyl group;

R 4 , R 5 , R 6 or R 7 represents a halogen atom, a lower alkyl group which may have a substituent, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, a nitro group or a formyl group;

m, n, p or q represents 0, 1 or 2;

in the case where m, n, p or q is 2, each R 4 , R 5 , R 6 or R 7 may be the same or different;

R 8 , R 9 , R 10 or R 11 represents a lower alkyl group which may have a substituent, a lower alkenyl group, a lower cycloalkyl group, an aryl group which may have a substituent or a heterocyclic group which may have a substituent;

R 12 and R 13 may be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent or a heterocyclic group.

2. The method according to claim 1 , wherein in formula (1),

R 1 represents formula (2a), (3a), (4a) or (5a)

R 2 represents —(CO)—R 8 , —(CO)O—R 9 , —(SO)—R 10 , —(SO 2 )—R 11 or —(CO)NR 12 R 13 ;

R 2 —O— is substituted at the 4- or -5-position of benzene ring A;

R 3 represents a lower alkyl group;

R 4 represents a halogen atom, a lower alkyl group, a lower alkoxy group or a nitro group;

R 5 represents a halogen atom, a lower alkyl group or a lower alkoxy group;

R 6 represents a halogen atom, a lower alkyl group or a lower alkoxy group;

R 7 represents a halogen atom or a lower alkyl group;

m, n or p represents 1 or 2;

in the case where m, n or p is 2, each R 4 , R 5 or R 6 may be the same or different;

q represents 1;

R 8 represents a lower alkyl group which may have a substituent, a lower alkenyl group, a lower cycloalkyl group, an aryl group which may have a substituent or a heterocyclic group which may have a substituent;

R 9 represents a lower alkyl group which may have a substituent or an aryl group which may have a substituent;

R 19 or R 11 represents a lower alkyl group which may have a substituent or a lower cycloalkyl group;

R 12 and R 13 may be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent or a heterocyclic group.

3. The method according to claim 1 , wherein in formula (1),

R 1 represents formula (2a-1), (2a-2), (2a-3), (3a-1), (3a-2), (4a-1), (4a-2), (4a-3), (5a-1) or (5a-2)

4. The method according to claim 3 , wherein in formula (1),

R 1 represents formula (2a-1), (2a-2), (2a-3), (3a-1), (3a-2), (4a-2) or (5a-1).

5. The method according to claim 1 , wherein in formula (1),

R 2 represents —(CO)—R 8 , —(CO)O—R 9 , —(SO 2 )—R 11 or —(CO)NR 12 R 13 .

6. The method according to claim 5 , wherein in formula (1),

R 2 represents —(CO)—R 8 or —(SO 2 )—R 11 .

7. The method according to claim 6 , wherein in formula (1),

R 2 represents —(CO)—R 8 .

8. The method according to claim 1 , wherein in formula (1),

R 3 represents a methyl group.

9. The method according to claim 1 , wherein in formula (1),

R 2 —O— is substituted at the 4-position of benzene ring A.

10. A method of treating an inflammatory disease or immune disease, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound or a salt thereof selected from the group consisting of:

6-[4-(Furan-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(2-methoxybenzoyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Butyryloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(thiophen-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[4-(furan-2-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-(4-isobutyryloxy-2-methoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-(2-methoxy-4-phenylacetoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[5-(furan-2-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-(2-methoxy-5-propionyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-5-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[4-(furan-3-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Acetoxybenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(2-methylthiobenzoyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(thiazol-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(5-methylfuran-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(3-methoxycarbonylbenzoyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(6-methylpyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-t-Butylcarbonyloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Chloropyridin-4-ylcarbonyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[4-(3-fluoropyridin-4-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-5-(2-methyl-5-nitrophenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(2-Methoxy-5-nitrophenoxymethyl)-6-[2-methoxy-4-(thiophen-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Benzoyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(Furan-3-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiophen-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(furan-2-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(3-methoxycarbonylbenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(4-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-methylthiobenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(6-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(4-Methylbenzoyloxymethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-methoxybenzoyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(Furan-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(4-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Benzoyloxy-2-methoxyphenyl)-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(thiophen-3-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(Furan-3-ylcarbonyloxy)-2-methoxyphenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-methylthiobenzoyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(thiazol-4-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(4-Methoxybenzoyloxymethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Bromothiophen-2-ylcarbonyloxymethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Bromothiophen-2-ylcarbonyloxymethyl)-6-[4-(furan-2-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Isopropylcarbonyloxy-2-methoxyphenyl)-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(2-Acetoxybenzoyloxy)-2-methoxyphenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(4-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(2-nitrobenzoyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Ethylsulfonyloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-(4-isopropylsulfonyloxy-2-methoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Butylsulfonyloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Cyclopropylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxy-5-nitrophenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Ethylsulfonyloxy-2-methoxyphenyl)-5-(2-methyl-5-nitrophenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(2-Methoxy-4-propylsulfonyloxyphenyl)-5-(2-methyl-5-nitrophenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Cyclopropylsulfonyloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(2-Methoxyphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(2-Methoxy-4-methylsulfonyloxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(3,3,3-trifluoropropylsulfonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(2-Methoxy-4-propylsulfonyloxyphenyl)-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Isopropylsulfonyloxy-2-methoxyphenyl)-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Cyclopentylsulfonyloxy-2-methoxyphenyl)-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Ethylsulfonyloxy-2-methoxyphenyl)-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Cyclopropylsulfonyloxy-2-methoxyphenyl)-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Dimethylaminocarbonyloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-[N-(2-Dimethylaminoethyl)-N-ethylaminocarbonyloxy]-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[4-(4-Chlorophenylaminocarbonyloxy)-2-methoxyphenyl]-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

5-(5-Fluoro-2-methylphenoxymethyl)-6-[2-methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,

6-(4-Dimethylaminocarbonyloxy-2-methoxyphenyl)-5-(2-methyl-5-nitrophenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,

6-[2-Methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline, and

6-(4-Dimethylaminocarbonyloxy-2-methoxyphenyl)-5-(5-methylthiophen-2-ylcarbonyloxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline.

11. The method according to claim 1 , wherein the inflammatory disease or immune disease is an ocular inflammatory disease or dermatitis.

12. The method according to claim 11 , wherein the ocular inflammatory disease is an inflammatory disease of anterior segment of eyeball.

13. The method according to claim 12 , wherein the inflammatory disease of anterior segment of eyeball is dry eye syndrome or allergic conjunctivitis.

14. The method according to claim 11 , wherein the ocular inflammatory disease is an inflammatory disease of posterior segment of eyeball.

15. The method according to claim 14 , wherein the inflammatory disease of posterior segment of eyeball is age-related macular degeneration, diabetic retinopathy or diabetic macular edema.

16. The method according to claim 11 , wherein the dermatitis is atopic dermatitis.

17. A method of treating an autoimmune disease, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound represented by formula (1) or a salt thereof:

wherein R 1 represents formula (2a), (3a), (4a) or (5a);

R 2 represents —(CO)—R 8 , —(CO)O—R 9 , —(SO)—R 10 , —(SO 2 )—R 11 or —(CO)NR 12 R 13 ;

R 2 —O— is substituted at the 4- or -5-position of benzene ring A;

R 3 represents a lower alkyl group;

R 4 , R 5 , R 6 or R 7 represents a halogen atom, a lower alkyl group which may have a substituent, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, a nitro group or a formyl group;

m, n, p or q represents 0, 1 or 2;

in the case where m, n, p or q is 2, each R 4 , R 5 , R 6 or R 7 may be the same or different;

R 8 , R 9 , R 19 or R 11 represents a lower alkyl group which may have a substituent, a lower alkenyl group, a lower cycloalkyl group, an aryl group which may have a substituent or a heterocyclic group which may have a substituent;

R 12 and R 13 may be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent or a heterocyclic group.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT PATENT NUMBER 7122598 PREVIOUSLY RECORDED ON REEL 037834 FRAME 0513. ASSIGNOR(S) HEREBY CONFIRMS THE PATENT NUMBER SHOULD BE 7112598. Recorded Apr 12, 2016
From: SANTEN PHARMACEUTICAL CO.,LTD.
To: AYUMI PHARMACEUTICAL CORPORATION
Reel/Frame 038408/0987 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 26, 2016
From: SANTEN PHARMACEUTICAL CO.,LTD.
To: AYUMI PHARMACEUTICAL CORPORATION
Reel/Frame 037834/0513 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 31, 2011
From: KATO, MASATOMO; TAKAI, MIWA; MATSUYAMA, TAKAHIRO; KUROSE, TATSUJI; HAGIWARA, YUMI; MATSUDA, MAMORU; MORI, TOSHIYUKI; IMOTO, KENJI; DOTA, ATSUYOSHI
To: SANTEN PHARMACEUTICAL CO., LTD.
Reel/Frame 025723/0509 →
Priority Claims (1)
JP 2008-124714 · May 12, 2008 · national
Continuity (1)
Related Publication 20110118260A1 · May 19, 2011