Imidazole derivative having protein kinase inhibitory activity, and use thereof
View Patent ↗The present invention relates to: a novel imidazole derivative compound; an isomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including the same. An imidazole derivative compound according to the present invention exhibits selective inhibitory activity against JNK, particularly JNK3, and thus can be used as a pharmaceutical composition for preventing and treating a degenerative brain disease (degenerative brain disease including Alzheimer's dementia, and Parkinson's disease).
1 . A compound of the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof:
in Chemical Formula 1,
R 1 is selected from the group consisting of
and a C 1 -C 6 alkyl,
R 2 is
herein,
n is an integer from 1 to 4,
m is an integer from 2 to 3,
carbon denoted as * is a chiral carbon,
Ar is selected from the group consisting of
and naphthalenyl,
R 3 and R 4 are each independently a halogen atom, and
Z is a carbon or oxygen atom.
2 . The compound of claim 1 , wherein the compound of Chemical Formula 1 has a structure of the following Chemical Formula 2:
in Chemical Formula 2,
R 1 is selected from the group consisting of
and a C 1 -C 6 alkyl,
n is an integer from 1 to 4,
m is an integer from 2 to 3,
Ar is selected from the group consisting of
and naphthalenyl,
R 3 and R 4 are each independently a halogen atom, and
Z is a carbon or oxygen atom.
3 . The compound of claim 1 , wherein the compound of Chemical Formula 1 has a structure of the following Chemical Formula 3:
in Chemical Formula 3,
R 1 is selected from the group consisting of
and a C 1 -C 6 alkyl,
Ar is selected from the group consisting of
and naphthalenyl,
R 3 and R 4 are each independently a halogen atom, and
Z is a carbon or oxygen atom.
4 . The compound of claim 1 , wherein the compound of Chemical Formula 1 has a structure of the following Chemical Formula 4:
in Chemical Formula 4,
R 1 is selected from the group consisting of
and a C 1 -C 6 alkyl,
n is an integer from 1 to 4,
m is an integer from 2 to 3,
Ar is selected from the group consisting of
and naphthalenyl,
R 3 and R 4 are each independently a halogen atom, and
Z is a carbon or oxygen atom.
5 . The compound of claim 1 , wherein the compound of Chemical Formula 1 has a structure of the following Chemical Formula 5:
in Chemical Formula 5,
R 1 is selected from the group consisting of
and a C 1 -C 6 alkyl,
Ar is selected from the group consisting of
and naphthalenyl,
R 3 and R 4 are each independently a halogen atom, and
Z is a carbon or oxygen atom.
6 . The compound of claim 1 , wherein the compound of Chemical Formula 1 has a structure of the following Chemical Formula 6:
in Chemical Formula 6,
R 1 is selected from the group consisting of
and a C 1 -C 6 alkyl,
Ar is selected from the group consisting of
R 3 and R 4 are each independently a halogen atom, and
Z is a carbon or oxygen atom.
7 . The compound of claim 1 , wherein the compound of Chemical Formula 1 has a structure of the following Chemical Formula 7:
in Chemical Formula 7,
R 1 is selected from the group consisting of
and a C 1 -C 6 alkyl,
Ar is
and
R 3 and R 4 are each independently a halogen atom.
8 . The compound of claim 1 , wherein the compound of Chemical Formula 1 has a structure of the following Chemical Formula 8:
in Chemical Formula 8,
R 1 is selected from the group consisting of
and a C 1 -C 6 alkyl,
Ar is selected from the group consisting of
and naphthalenyl,
R 3 and R 4 are each independently a halogen atom, and
Z is a carbon or oxygen atom.
9 . The compound of claim 1 , wherein the compound of Chemical Formula 1 is
(S)-(1-(2-((1-(cyclopropanecarbonyl)piperidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(4-hydroxypiperidin-1-yl)methanone;
(S)-(1-(2-((1-(cyclopropanecarbonyl)piperidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-carboxamide;
(R)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-carboxamide;
(S)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(S)-1-(2-((1-(cyclobutanecarbonyl)piperidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(S)-1-(2-((1-(cyclopentanecarbonyl)piperidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(S)-1-(2-((1-(cyclopropanecarbonyl)piperidin-3-yl)amino)pyrimidin-4-yl)-2-(naphthalen-2-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(R)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(naphthalen-2-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(S)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(S)-2-(benzo[d][1,3]dioxol-5-yl)-1-(2-((1-(cyclopropanecarbonyl)piperidin-3-yl)amino)pyrimidin-4-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(R)-2-(benzo[d][1,3]dioxol-5-yl)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(S)-2-(benzo[d][1,3]dioxol-5-yl)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(S)-2-(benzo[d][1,3]dioxol-5-yl)-1-(2-((1-(cyclobutanecarbonyl)piperidin-3-yl)amino)pyrimidin-4-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(S)-1-(2-((1-(cyclopropanecarbonyl)piperidin-3-yl)amino)pyrimidin-4-yl)-2-(2,3-dihydrobenzofuran-5-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide;
(R)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(2,3-dihydrobenzofuran-5-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide; or
(S)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(2,3-dihydrobenzofuran-5-yl)-4,6-dihydropyrrolo[3,4-d]imidazole-5(1H)-carboxamide.
10 . A pharmaceutical composition for preventing or treating a degenerative brain disease, comprising the compound or the pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.
11 . A method for treating a degenerative brain disease, comprising administering an effective amount of the compound or the pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.
12 . The method of claim 11 , wherein the degenerative brain disease is Alzheimer's dementia or Parkinson's disease.
13 . The method of claim 11 , wherein the compound inhibits the activity of c-Jun N-terminal kinase 3 (JNK3).