Bicycloaniline derivative

1. A compound of a general formula (I):

wherein,

A 1 and A 2 each independently mean a nitrogen atom, or mean a methine group optionally substituted with a halogen atom, a hydroxyl group, a cyano group, a C1-C6 alkyl group, a C1-C6 alkoxy group or a hydroxy-C1-C6 alkyl group;

Ring B means a 5-membered to 7-membered aliphatic ring condensed with a ring of formula (a):

or means a spiro or bicyclo ring formed from the 5-membered to 7-membered aliphatic ring with any other 3-membered to 7-membered aliphatic ring, which is condensed with the ring of formula (a), in which one or two or more methylene groups constituting said Ring B may be independently replaced by an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group, a carbonyl group or a group of —N(R 1a )—, and one or two or more methylene groups constituting said Ring B may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a -N(R 1b )R 1c ;

Cy means an aryl or heterocyclic group optionally substituted with a halogen atom or a C1-C6 alkyl group;

Q 1a , Q 1b , Q 1d and Q 1e each independently mean a single bond or a C1-C6 alkylene group, in which one or two or more methylene groups constituting the C1-C6 alkylene group may be independently replaced by a sulfinyl group, a sulfonyl group or a carbonyl group;

R 1 means a hydrogen atom, or means a C1-C6 alkyl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C2-C7 alkanoyl group and a C1-C6 alkylsulfonyl group, or means an aryl, aralkyl or heteroaryl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, an amino group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a halo-C 1-C6 alkyl group and a hydroxy-C1-C6 alkyl group;

R 2 means an aryl, aralkyl or heteroaryl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, an amino group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a halo-C1-C6 alkyl group and a hydroxy-C1-C6 alkyl group;

R 1a means a hydrogen atom, or means a C1-C6 alkyl, C3-C6 cycloalkyl or C2-C7 alkanoyl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group and a C2-C7 alkanoyl group, or means a group of -Q 1b -Cy or -Q 1d —N(R 1f )R 1g ;

R 1b and R 1c each independently mean a hydrogen atom, or mean a C1-C6 alkyl, C2-C7 alkanoyl or C1-C6 alkylsulfonyl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C2-C7 alkanoyl group and a C1-C6 alkylsulfonyl group, or mean a group of -Q 1e -N(R 1h )R 1i ;

R 1f and R 1g each independently mean a hydrogen atom, or mean a C1-C6 alkyl, C2-C7 alkanoyl or C1-C6 alkylsulfonyl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C2-C7 alkanoyl group and a C1-C6 alkylsulfonyl group;

R 1h and R 1i each independently mean a hydrogen atom, or mean a C1-C6 alkyl, C2-C7 alkanoyl or C1-C6 alkylsulfonyl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C2-C7 alkanoyl group and a C1-C6 alkylsulfonyl group; and

X means a group of ═NH or ═O, or a pharmaceutically acceptable salt thereof.

2. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 1 , wherein X is ═NH.

3. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 2 , wherein R 1 is a hydrogen atom, or a C1-C6 alkyl group optionally substituted with a halogen atom or a hydroxyl group.

4. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 3 , wherein R 2 is a phenyl or pyridyl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, an amino group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a halo-C1-C6 alkyl group and a hydroxy-C1-C6 alkyl group.

5. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 2 , wherein A 1 and A 2 are both unsubstituted methine groups.

6. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 5 , wherein the 5-membered to 7-membered aliphatic ring condensed with the ring of formula (a) of Ring B is a ring selected from a group consisting of a formula (b-1):

the spiro ring condensed with the ring of formula (a) is a ring selected from a group consisting of a formula (b-2):

and the bicyclo ring condensed with the ring of formula (a) is a ring selected from a group consisting of a formula (b-3):

in which one or two or more methylene groups constituting said Ring B may be independently replaced by a an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group, a carbonyl group or a group of —N(R 1a )—, and one or two or more methylene groups constituting said Ring B may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a —N(R 1b )R 1c .

7. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 6 , wherein a group of formula (ab-1):

is a group selected from a group consisting of a formula (b-10):

wherein, R 2a means a hydrogen atom, or means a C1-C6 alkyl, C3-C6 cycloalkyl or C2-C7 alkanoyl group optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a cyano group, a C1-C6 alkoxy group, a C3-C6cycloalkyl group and a C2-C7 alkanoyl group, or means a group of or -Q 1b -Cy or -Q 1d -N(R 1f )R 1g ; Cy, Q 1b , Q 1d , R 1f and R 1g have the same meanings as in claim 1 , in which one or two or more methylene groups constituting the aliphatic ring of the group may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a -N(R 1b )R 1c .

8. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 7 , wherein the group of formula (ab-1):

is a group selected from a group consisting of a formula (b-11):

in which one or two or more methylene groups constituting the aliphatic ring of the group may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a -N(R 1b )R 1c .

9. The compound, or a pharmaceutically acceptable salt or thereof as claimed in claim 8 , wherein the group of formula (ab-1):

is a group selected from a group consisting of a formula (b-12):

in which one or two or more methylene groups constituting the aliphatic ring of the group may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a -N(R 1b )R 1c .

10. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 6 , wherein the group of formula (ab-1):

is a group selected from a group consisting of a formula (b-20):

in which one or two or more methylene groups constituting the aliphatic ring of the group may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a -N(R 1b )R 1c .

11. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 10 , wherein the group of formula (ab-1):

is a group selected from a group consisting of a formula (b-21):

in which one or two or more methylene groups constituting the aliphatic ring of the group may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a -N(R 1b )R 1c .

12. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 11 , wherein the group of formula (ab-1):

is a group of a formula (b-22):

in which one or two or more methylene groups constituting the aliphatic ring of the group may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a -N(R 1b )R 1c .

13. The compound, or a pharmaceutically acceptable salt thereof as claimed in claim 6 , wherein the group of formula (ab-1):

is a group selected from a group consisting of a formula (b-30):

in which one or two or more methylene groups constituting the aliphatic ring of the group may be independently substituted with a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group or a group of -Q 1a -N(R 1b )R 1c .

14. The compound as claimed in claim 1 , which is selected from the following compounds:

(1) 3-(2,6-dichlorophenyl)-4-imino-7-[(2′-methyl-2′,3′-dihydro spiro[cyclopropane-1,4′-isoquinolin]-7′-yl)amino]-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(2) 3-(2,6-dichlorophenyl)-4-imino-7-{[2,4,4-trimethyl-1,2,3,4-tetrahydroisoquinolin-7-yl]amino}-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(3) 3-(2,6-dichlorophenyl)-4-imino-7-[(1,1,2-trimethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)amino]-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(4) 3-(2,4-dichloropyridin-3-yl)-4-imino-7-{[1,1,2-trimethyl-1,2,3,4-tetrahydroisoqunolin-6-yl]amino}-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(5) 3-(2,6-dichlorophenyl)-4-imino-7-[(1,1,2-trimethyl-2,3-dihydro-1H-isoindol-5-yl)amino]-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(6) 3-(2,6-dichlorophenyl)-7-{[2-(dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}-4-imino-1-methyl-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(7) 3-(2,6-dichlorophenyl)-7-{[3-(dimethylamino)-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl]amino}-4-imino-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(8) 3-(2-chloro-6-methylphenyl)-4-imino-7-[(2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-yl)amino]-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one;

(9) 3-(2-chloro-6-fluorophenyl)-4-imino-7-[2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl]amino-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one;

(10) 3-(2-chloro-4,6-difluorophenyl)-4-imino-7-{[2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl]amino}-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(11) 3-(2,6-dichloro-4-fluorophenyl)-4-imino-7-{[2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl]amino}-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(12) 3-(2,6-dichlorophenyl)-7-{[2,5-dimethyl-1,2,3,4-tetrahydroisoquinolin-7-yl]amino}-4-imino-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one;

(13) 3-(2,6-dichlorophenyl)-7-[2-(2-hydroxyethyl)-1,1-dimethyl-1,2,3,4-tetrahydroisoquinolin-6-yl]amino-4-imino-1-methyl-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one;

(14) 3-(2,6-dichlorophenyl)-4-imino-7-{[2-ethyl-1,2,3,4-tetrahydroisoquinolin-6-yl]amino}-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one;

(15) 3-(2,6-dichlorophenyl)-4-imino-7-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)amino]-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(16) 3-(2,6-dichlorophenyl)-7-{[2-(dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}-4-imino-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one;

(17) 3-(2,6-dichlorophenyl)-7-{[7-(dimethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]amino}-4-imino-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(18) 3-(2,6-dichlorophenyl)-4-imino-7-[(3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)amino]-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

(19) 3-(2,6-dichlorophenyl)-7-{6-[(dimethylamino)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl}amino)-4-imino-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one; or

(20) 7-[(2-acetyl-1,1-dimethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)amino]-3-(2,6-dichlorophenyl)-4-imino-3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one;

or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.