Preventive and/or therapeutic agent of immune disease

1. A method for treating an immune disease, comprising:

administering an effective amount of a compound of the formula (I) or a salt thereof to an object in need thereof,

wherein X represents a nitrogen-containing C3-C10 heterocycloalkylene optionally having one or more substituents;

Y represents —C(R 4 )═C(R 5 )(R 6 ) or —C≡C—R 7 ;

W and Z each independently represent N or CH;

n represents an integer from 0 to 2;

R 1 represents an amino group which optionally has one or more substituents;

R 2 and R 3 , which are identical or different, each represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group which optionally has one or more substituents, a C1-C6 alkoxy group which optionally has one or more substituents, a C3-C7 cycloalkyl group which optionally has one or more substituents, a C6-C14 aromatic hydrocarbon group which optionally has one or more substituents, a 4- to 10-membered monocyclic or polycyclic unsaturated heterocyclic group containing 1 to 3 heteroatoms of the same kind or different kinds selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which optionally has one or more substituents, or a cyano group; and

R 4 , R 5 , R 6 and R 7 , which are identical or different, each represent a hydrogen atom, or a C1-C6 alkyl group which optionally has one or more substituents.

2. The method of claim 1 , wherein in the formula (I),

X represents a nitrogen-containing C3-C10 heterocycloalkylene;

n represents 0; and

R 1 represents an amino group.

3. The method of claim 1 , wherein in the formula (I),

X represents azetidinylene, pyrrolidinylene, or piperidinylene;

n represents 0; and

R 1 represents an amino group.

4. The method according to of claim 1 , wherein in the formula (I),

X represents azetidinylene, pyrrolidinylene, or piperidinylene;

Y represents —C(R 4 )═C(R 5 )(R 6 ) or —C≡C—R 7 ;

n represents 0;

R 1 represents an amino group;

one of R 2 and R 3 represents a hydrogen atom or a C1-C6 alkyl group, and the other represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halogeno-C1-C6 alkyl group, a C1-C4 alkoxy-substituted C1-C6 alkyl group, a C1-C6 alkoxy group, a phenyl group which optionally has one or more substituents with a halogen atom, a 4- to 6-membered monocyclic unsaturated heterocyclic group containing one sulfur atom, or a cyano group;

when Y represents —C(R 4 )═C(R 5 )(R 6 ),

R 4 , R 5 and R 6 , which are identical or different, each represent a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkyl group that is substituted with an amino group substituted with two C1-C6 alkyl groups, where the C1-C6 alkyl groups optionally form a 4- to 8-membered heterocycloalkyl group together with the nitrogen atom to which these alkyl groups are bonded; and

when Y represents —C≡C—R 7 ,

R 7 represents a hydrogen atom or a C1-C6 alkyl group.

5. The method of claim 1 , wherein in the formula (I),

X represents 1,3-azetidinylene, 1,3-pyrrolidinylene, or 1,3-piperidinylene;

Y represents —C(R 4 )═C(R 5 )(R 6 ) or —C≡C—R 7 ;

when Z represents N, W represents N, and when Z represents CH, W represents N or CH;

n represents 0;

R 1 represents an amino group;

one of R 2 and R 3 represents a hydrogen atom or a C1-C4 alkyl group, and the other represents a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a halogeno-C1-C4 alkyl group, a C1-C4 alkoxy-substituted C1-C4 alkyl group, a C1-C4 alkoxy group, a phenyl group which optionally has one or more substituents with a halogen atom, a 4- to 6-membered monocyclic unsaturated heterocyclic group containing one sulfur atom, or a cyano group;

when Y represents —C(R 4 )═C(R 5 )(R 6 ),

R 4 , R 5 and R 6 , which are identical or different, each represent a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkyl group that is substituted with an amino group substituted with two C1-C6 alkyl groups, where the C1-C6 alkyl groups optionally form a 4- to 8-membered heterocycloalkyl group together with the nitrogen atom to which these alkyl groups are bonded; and

when Y represents —C≡C—R 7 ,

R 7 represents a hydrogen atom or a C1-C4 alkyl group.

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

X represents 1,3-azetidinylene, 1,3-pyrrolidinylene, or 1,3-piperidinylene;

Y represents —C(R 4 )═C(R 5 )(R 6 ) or —C≡C—R 7 ;

when Z represents N, W represents N, and when Z represents CH, W represents N or CH;

n represents 0;

R 1 represents an amino group;

one of R 2 and R 3 represents a hydrogen atom or a methyl group, and the other represents a hydrogen atom, a halogen atom, a methyl group, a trifluoromethyl group, a methoxyethyl group, a methoxy group, a phenyl group, a 4-chlorophenyl group, a 2-thienyl group, or a cyano group;

when Y represents —C(R 4 )═C(R 5 )(R 6 ),

R 4 , R 5 and R 6 , which are identical or different, each represent a hydrogen atom, a methyl group, a dimethylaminomethyl group, a methylethylaminomethyl group, a diethylaminomethyl group, a methylisopropylaminomethyl group, a 1-piperidinylmethyl group, or a 1-pyrrolidinylmethyl group; and

when Y represents —C≡C—R 7 ,

R 7 represents a methyl group.

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

(1) when Z represents N, and W represents N,

X represents 1,3-piperidinylene, and

Y represents a vinyl group;

(2) when Z represents CH, and W represents N,

X represents 1,3-pyrrolidinylene or 1,3-piperidinylene, and

Y represents —C(R 4 )═C(R 5 )(R 6 ) or —C≡C—(R 7 ), and

when Y represents —C(R 4 )═C(R 5 )(R 6 ),

R 4 , R 5 and R 6 , which are identical or different, each represent a hydrogen atom, a methyl group, a dimethylaminomethyl group, a methylethylaminomethyl group, a diethylaminomethyl group, a methylisopropylaminomethyl group, a 1-piperidinylmethyl group, or a 1-pyrrolidinylmethyl group;

when Y represents —C≡C—(R 7 ),

R 7 represents a methyl group; and

(3) when Z represents CH, and W represents CH,

X represents 1,3-azetidinylene or 1,3-pyrrolidinylene, and

Y represents —C(R 4 )═C(R 5 )(R 6 ), and

R 4 , R 5 and R 6 , which are identical or different, each represent a hydrogen atom, a dimethylaminomethyl group, a methylethylaminomethyl group, a diethylaminomethyl group, a methylisopropylaminomethyl group, a 1-piperidinylmethyl group, or a 1-pyrrolidinylmethyl group;

n represents 0;

R 1 represents an amino group;

one of R 2 and R 3 represents a hydrogen atom or a methyl group, and the other represents a hydrogen atom, a halogen atom, a trifluoromethyl group, a methoxyethyl group, a phenyl group, a 2-thienyl group, or a cyano group.

8. The method of claim 1 , wherein in the formula (I),

X represents 1,3-piperidinylene;

Y represents a vinyl group;

Z represents CH;

W represents N;

n represents 0;

R 1 represents an amino group; and

one of R 2 and R 3 represents a hydrogen atom, and the other represents a hydrogen atom, a halogen atom, or a cyano group.

9. The method of claim 1 , wherein the compound of the formula (I) or a salt thereof is selected from the group consisting of:

(1) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(2) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5-bromobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(3) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5-(thiophen-2-yl)benzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(4) (R)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-methacryloylpiperidin-3-yl)-1H-pyrazol o[3,4-d]pyrimidine-3-carboxamide,

(5) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(6) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5-cyanobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(7) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5-methoxybenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(8) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5-(2-methoxyethyl)benzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(9) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(oxazolo[4,5-b]pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(10) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(4-methylbenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(11) (R)-4-amino-N-(5-fluorobenzo[d]oxazol-2-yl)-1-(1-methacryloylpiperidin-3-yl)-1H-pyrazol o[3,4-d]pyrimidine-3-carboxamide,

(12) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5-fluorobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(13) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(benzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(14) (R,E)-4-amino-N-(benzo[d]oxazol-2-yl)-1-(1-(but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(15) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-(dimethylamino)but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(16) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-ethyl(methyl)amino)but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(17) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-di ethylamino)but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(18) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-isopropyl(methyl)amino)but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(19) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-(pyrrolidin-1-yl)but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(20) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-(piperidin-1-yl)but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(21) (R,E)-4-amino-N-(5-(thiophen-2-yl)benzo[d]oxazol-2-yl)-1-(1-(4-(dimethylamino)but-2-enoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(22) (R)-4-amino-N-(benzo[d]oxazol-2-yl)-1-(1-but-2-ynoyl)piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(23) (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5,6-dimethylbenzo[d]oxazol-2-yl)-1H-pyrazol o[3,4-d]pyrimidine-3-carboxamide,

(24) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(25) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(26) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(3-methylbut-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(27) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(benzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(28) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-(thiophen-2-yl)benzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(29) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-methylbenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(30) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-fluorobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(31) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N chlorophenyl)benzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(32) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(33) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-ethyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(34) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-diethylamino)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(35) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-isopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(36) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-(pyrrolidin-1-yl)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(37) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1-(1-(4-(piperidin-1-yl)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(38) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-methoxybenzo[d]oxazol-2-yl)-1H-pyrazol o[3,4-d]pyrimidine-3-carboxamide,

(39) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-cyanobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(40) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-(2-methoxyethyl)benzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(41) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(42) (R,E)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-1-(1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(43) (R)-1-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(44) (R,E)-4-amino-N-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)-1-(1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazol o[3,4-d]pyrimidine-3-carboxamide,

(45) 1-(1-acryloylazetidin-3-yl)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(46) 7-(1-acryloylazetidin-3-yl)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7H-pyrrol o[2,3-d]pyrimidine-5-carboxamide,

(47) (E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7-(1-(4-(dimethylamino)but-2-enoyl)azetidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(48) (R)-7-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(49) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7-(1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(50) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7-(1-(4-(ethyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(51) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7-(1-(4-(diethylamino)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(52) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7-(1-(4-(isopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(53) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7-(1-(4-(pyrrolidin-1-yl)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(54) (R,E)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-7-(1-(4-(piperidin-1-yl)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(55) (R)-7-(1-acryloylpyrrolidin-3-yl)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(56) (R,E)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-7-(1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(57) (R,E)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-7-(1-(4-(ethyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(58) (R,E)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-7-(1-(4-(diethylamino)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(59) (R,E)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-7-(1-(4-(isopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(60) (R,E)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-7-(1-(4-(pyrrolidin-1-yl)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,

(61) (R,E)-4-amino-N-(5-phenylbenzo[d]oxazol-2-yl)-7-(1-(4-(piperidin-1-yl)but-2-enoyl)pyrrolidin-3-yl) 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide, and

a salt thereof.

10. The method of claim 1 , wherein the immune disease is an allergic disease, an autoimmune disease, or an inflammatory disease.

11. The method of claim 1 , wherein the immune disease is atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, allergic rhinitis, or pollinosis.

12. The method of claim 1 , wherein the immune disease is rheumatoid arthritis.

13. The method of claim 2 , wherein the immune disease is an allergic disease, an autoimmune disease, or an inflammatory disease.

14. The method of claim 9 , wherein the immune disease is an allergic disease, an autoimmune disease, or an inflammatory disease.

15. The method of claim 2 , wherein the immune disease is atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, allergic rhinitis, or pollinosis.

16. The method of claim 9 , wherein the immune disease is atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, allergic rhinitis, or pollinosis.

17. The method of claim 2 , wherein the immune disease is rheumatoid arthritis.

18. The method of claim 4 , wherein the immune disease is rheumatoid arthritis.

19. The method of claim 7 , wherein the immune disease is rheumatoid arthritis.

20. The method of claim 9 , wherein the immune disease is rheumatoid arthritis.