Purinone derivative

1. A compound represented by general formula (I)

(in the formula,

L represents (1) —O—, (2) —S—, (3) —SO—, (4) —SO 2 — (5) —NH—, (6) —C(O)—, (7) —CH 2 —O—, (8) —O—CH 2 —, (9) —CH 2 —, or (10) —CH(OH)—;

R 1 represents (1) a halogen atom, (2) a C 1-4 alkyl group, (3) a C 1-4 alkoxy group, (4) a C 1-4 haloalkyl group, or (5) a C 1-4 haloalkoxy group;

ring1 represents a benzene, cyclohexane, or pyridine ring, which may be substituted by from one to five substituents each independently selected from the group consisting of (1) halogen atoms, (2) C 1-4 alkyl groups, (3) C 1-4 alkoxy groups, (4) nitrile, (5) C 1-4 haloalkyl groups, and (6) C 1-4 haloalkoxy groups, wherein when two or more substituents are present on ring1, these substituents may form a 4- to 7-membered cyclic group together with the atoms in ring1 to which these substituents are bound;

ring2 represents a 4- to 6-membered nitrogenous saturated heterocycle, which is substituted by from one to three —K—R 2 ;

K represents C(O), (wherein the bond on the left is bound to the ring2);

R 2 represents (1) a C 1-4 alkyl, (2) a C 2-4 alkenyl, or (3) a C 2-4 alkynyl group, each of which may be substituted by from one to five substituents each independently selected from the group consisting of (1) NR 3 R 4 , (2) halogen atoms, (3) CONR 5 R 6 , (4) CO 2 R 7 , and (5) OR 8 ;

R 3 and R 4 each independently represent (1) a hydrogen atom, or (2) a C 1-4 alkyl group which may be substituted by OR 9 or CONR 10 R 11 ;

R 3 and R 4 may, together with the nitrogen atom to which they are bound, form a 4- to 7-membered nitrogenous saturated heterocycle, which may be substituted by an oxo group or a hydroxyl group;

R 5 and R 6 each independently represent (1) a hydrogen atom, (2) a C 1-4 alkyl group, or (3) a phenyl group;

R 7 represents (1) a hydrogen atom or (2) a C 1-4 alkyl group;

R 8 represents (1) a hydrogen atom, (2) a C 1-4 alkyl group, (3) a phenyl group, or (4) a benzotriazolyl group;

R 9 represents (1) a hydrogen atom or (2) a C 1-4 alkyl group;

R 10 and R 11 each independently represent (1) a hydrogen atom or (2) a C 1-4 alkyl group;

n represents an integer from 0 to 4;

m represents an integer from 0 to 2; and

when n is two or more, the R 1 's may be the same as each other or may differ from one another),

an optical isomer thereof or their mixture, a salt thereof, a solvate thereof, or an N-oxide thereof.

2. The compound according to claim 1 , wherein R 2 is a C 2-4 alkenyl group or a C 2-4 alkynyl group, each of which may be substituted by from one to five substituents each independently selected from the group consisting of (1) NR 3 R 4 , (2) halogen atoms, (3) CONR 5 R 6 , (4) CO 2 R 7 , and (5) OR 8 .

3. The compound according to claim 1 , wherein the 4- to 6-membered nitrogenous saturated heterocycle is an azetidine, pyrrolidine, or piperidine ring.

4. The compound according to claim 1 , represented by general formula (I-1)

(in the formula, ring1-1 represents a benzene, cyclohexane, or pyridine ring, each of which may be substituted by from one to five substituents each independently selected from the group consisting of (1) halogen atoms, (2) C 1-4 alkyl groups, (3) C 1-4 alkoxy groups, (4) nitrile, and (5) CF 3 , and ring2-1 represents a 4- to 6-membered nitrogenous saturated heterocycle, which is substituted by from one to three —K—R 2 , wherein the other symbols have the same definitions as above).

5. The compound according to claim 4 , wherein R 2 is a C 2-4 alkenyl group or a C 2-4 alkynyl group, each of which may be substituted by from one to five substituents each independently selected from the group consisting of (1) NR 3 R 4 , (2) halogen atoms, (3) CONR 5 R 6 , (4) CO 2 R 7 , and (5) OR 8 .

6. The compound according to claim 1 , which is

(1) 9-(1-acryloyl-3-azetidinyl)-6-amino-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one,

(2) 6-amino-9-{(3R)-1-[(2E)-4-(dimethylamino)-2-butenoyl]-3-pyrrolidinyl}-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one,

(3) 9-[(1-acryloyl-4-piperidinyl)methyl]-6-amino-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one,

(5) 6-amino-9-{(3S)-1-[(2E)-4-(dimethylamino)-2-butenoyl]-3-pyrrolidinyl}-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one,

(6) 6-amino-7-[4-(3-chlorophenoxy)phenyl]-9-{(3R)-1-[(2E)-4-(dimethylamino)-2-butenoyl]-3-pyrrolidinyl}-7,9-dihydro-8H-purin-8-one,

(7) 6-amino-9-[1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one, or

(8) 6-amino-9-{1-[(2E)-4-(dimethylamino)-2-butenoyl]-3-pyrrolidinyl}-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one, or an optical isomer thereof or their mixture.

7. A pharmaceutical composition comprising a compound represented by general formula (I) according to claim 1 , an optical isomer thereof or their mixture, a salt thereof, a solvate thereof, or an N-oxide thereof.

8. The pharmaceutical composition according to claim 7 , that is a Btk inhibitor.

9. The pharmaceutical composition according to claim 8 , that is a therapeutic agent for a non-Hodgkin's lymphoma.

10. The pharmaceutical composition according to claim 7 , which is an inhibitor of B-cell activation.

11. A method of treating a Btk-related disease, comprising administering to a mammal of an effective amount of a compound represented by general formula (I) according to claim 1 , an optical isomer thereof or their mixture, a salt thereof, a solvate thereof, or an N-oxide thereof, wherein the Btk-related disease is a non-Hodgkin's lymphoma.