Pyrazole compounds and pharmaceutical compositions comprising the compound
The present invention provides a novel compound having an excellent JNK inhibitory effect. That is, it provides a compound represented by the following formula, a salt thereof or a hydrate of them. Wherein R 1 designates —(CO h —(NR a ) j —(CR b ═CR c ) k —Ar (wherein R a , R b and R c each independently designate a hydrogen atom, a halogen atom, hydroxyl group, an optionally substituted C 1-6 alkyl group or the like; Cy designates a 5- or 6-membered heteroaryl; and V each independently designate the formula -L-X—Y (wherein L designates a single bond, an optionally substituted C 1-6 alkylene group or the like; X designates a single bond or the formula -A- (wherein A designates NR 2 , O, CO, S, SO or SO 2 ) and so on; and Y designates a hydrogen atom, a halogen atom, nitro group or the like).
1 . A compound represented by the formula (I), a salt thereof or a hydrate of them.
Wherein, R 1 designates a group represented by the formula —(CO h —(NR a ) j —(CR b ═CR c ) k —Ar (wherein R a , R b and R c each independently designate a hydrogen atom, halogen atom, hydroxyl group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 2-6 alkenyloxy group, an optionally substituted C 1-6 alkylthio group, an optionally substituted C 2-6 alkenylthio group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group; Ar designates an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group; and h, j and k each independently designate 0 or 1);
Cy designates a 5- to 6-membered heteroaryl group;
V designates a group represented by the formula -L-X—Y (wherein, L designates a single bond, an optionally substituted C 1-6 alkylene group, an optionally substituted C 2-6 alkenylene group or an optionally substituted C 2-6 alkynylene group; X designates a single bond, or a group represented by —NR 7 —, —O—, —CO—, —S—, —SO—, —SO 2 —, —CO—NR 8 -Z-, —C(O)O—, —NR 8 —CO-Z-, —NR 8 —C(O)O—, —NR 8 —S—, —NR 8 —SO—, —NR 8 —SO 2 -Z-, —NR 9 —CO—NR 10 —, —NR 9 —CS—NR 10 —, —S(O) m —NR 11 -Z-, —C(═NR 12 )—NR 13 —, —OC(O)—, —OC(O)—NR 14 — or —CH 2 —NR 8 —COR 7 — (wherein R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 each independently designate a hydrogen atom, halogen atom, hydroxyl group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 2-6 alkenyloxy group, an optionally substituted C 1-6 alkylthio group, an optionally substituted C 2-6 alkenylthio group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group, Z designates a single bond or an optionally substituted C 1-6 alkylene group, and m designates 0, 1 or 2);
Y designates any one group selected from the group consisting of a hydrogen atom, halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group or an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group, an optionally substituted 5- to 14-membered heteroaryl group, an optionally substituted amino group and a group represented by the formula —W—R 15 (wherein W designates CO or SO 2 ; R 15 designates an optionally substituted C 1-6 alkyl group, an optionally substituted amino group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group)); and
n designates 0, 1, 2, 3 or 4, and when n is 2 or more, plural Vs each independently designate -L-X—Y as defined above.
2 . The compound according to claim 1 , a salt thereof or a hydrate of them, wherein Cy forms a 5-membered heteroaryl group.
3 . The compound according to claim 1 , a salt thereof or a hydrate of them, wherein Cy forms a thiophene ring.
4 . The compound according to claim 1 , a salt thereof or a hydrate of them, wherein in the formula (I), the partial structure consisting of Cy and the pyrazole ring adjoining to the Cy is 1H-thieno[2,3-c]pyrazole.
5 . A compound represented by the formula (II), a salt thereof or a hydrate of them.
Wherein,
Q 1 to Q 4 each independently designate —NV 1 —, —CV 2 ═, —N═, —N(→O)═ or —CO—, and at least one of Q 1 to Q 4 designates —NV 1 — or —N═, —N(→O)═; and
R 1 designates a group represented by the formula —(CO) h —(NR a ) j —(CR b ═CR c ) k —Ar (wherein R a , R b and R c each independently designate a hydrogen atom, halogen atom, hydroxyl group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 2-6 alkenyloxy group, an optionally substituted C 1-6 alkylthio group, an optionally substituted C 2-6 alkenylthio group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group; Ar designates an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group; and h, j and k each independently designate 0 or 1),
V 1 and V 2 each independently designate a group represented by the formula -L-X—Y (wherein, L designates a single bond, an optionally substituted C 1-6 alkylene group, an optionally substituted C 2-6 alkenylene group or an optionally substituted C 2-6 alkynylene group;
X designates a single bond, or a group represented by —NR 7 —, —O—, —CO—, —S—, —SO—, —SO 2 —, —CO—NR 8 -Z-, —C(O)O—, —NR 8 —CO-Z-, —NR 8 —C(O)O—, —NR 8 —S—, —NR 8 —SO—, —NR 8 —SO 2 -Z-, —NR 9 —CO—NR 10 —, —NR 9 —CS—NR 10 —, —S(O) m —NR 11 -Z-, —C(═NR 12 )—NR 13 —, —OC(O)—, —OC(O)—NR 14 — or —CH 2 —NR 8 —COR 7 — (wherein R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 each independently designate a hydrogen atom, halogen atom, hydroxyl group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 2-6 alkenyloxy group, an optionally substituted C 1-6 alkylthio group, an optionally substituted C 2-6 alkenylthio group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group, Z designates a single bond or an optionally substituted C 1-6 alkylene group, and m designates 0, 1 or 2); and
Y designates any one group selected from the group consisting of a hydrogen atom, halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group or an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group, an optionally substituted 5- to 14-membered heteroaryl group, an optionally substituted amino group and a group represented by the formula —W—R 15 (wherein W designates CO or SO 2 ; and R 15 designates an optionally substituted C 1-6 alkyl group, an optionally substituted amino group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group).
6 . The compound according to claim 5 , a salt thereof or a hydrate of them, wherein among Q 1 to Q 4 , either one is —N═, and the others are —CV 2 ═.
7 . The compound according to claim 5 , a salt thereof or a hydrate of them, wherein among Q 1 to Q 4 , either one of Q 1 , Q 3 and Q 4 is —N═, and the others are —CV 2 ═.
8 . The compound according to claim 6 , a salt thereof or a hydrate of them, wherein Q 1 is —N═.
9 . The compound according to claim 6 , a salt thereof or a hydrate of them, wherein Q 2 is —N═.
10 . The compound according to claim 6 , a salt thereof or a hydrate of them, wherein Q 3 is —N═.
11 . The compound according to claim 6 , a salt thereof or a hydrate of them, wherein Q 4 is —N═.
12 . The compound according to claim 5 , a salt thereof or a hydrate of them, wherein among Q 1 to Q 4 , either two are —N═, and the others are —CV 2 ═.
13 . The compound according to claim 12 , a salt thereof or a hydrate of them, wherein among Q 1 to Q 4 , either two of Q 1 , Q 3 and Q 4 are —N═, and the others are —CV 2 ═.
14 . The compound according to any one of claims 5 to 13 , a salt thereof or a hydrate of them, wherein when either of Q 1 , Q 3 and Q 4 is —CV 2 ═, the —CV 2 ═ in Q 1 , Q 3 or Q 4 is —CH═.
15 . The compound according to claim 5 , a salt thereof or a hydrate of them, wherein among Q 1 to Q 4 , either three are —N═, and the other is —CV 2 ═.
16 . The compound according to claim 15 , a salt thereof or a hydrate of them, wherein Q 1 , Q 3 and Q 4 are —N═.
17 . The compound according to claim 5 , a salt thereof or a hydrate of them, wherein among Q 1 to Q 4 , at least one is —CO—.
18 . The compound according to claim 5 , a slat thereof or a hydrate of them, wherein Q 1 is —CO—, Q 2 is —NV 1 —, and Q 3 and Q 4 are —CV 2 ═.
19 . The compound according to claim 5 , a slat thereof or a hydrate of them, wherein Q 3 is —CO—, Q 2 is —NV 1 —, and Q 1 and Q 4 are —CV 2 ═.
20 . A compound represented by the formula (III), a salt thereof or a hydrate of them.
Wherein
R 1 designates a group represented by the formula —(CO) h —(NR a ) j —(CR b ═CR c ) k —Ar (wherein R a , R b and R c each independently designate a hydrogen atom, halogen atom, hydroxyl group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 2-6 alkenyloxy group, an optionally substituted C 1-6 alkylthio group, an optionally substituted C 2-6 alkenylthio group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group; Ar designates an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group; and h, j and k each independently designate 0 or 1, provided that when h and j are 0, k is 1);
R d , R e and R f each independently designate a hydrogen atom, halogen atom, hydroxyl group, cyano group, nitro group, carboxyl group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 2-7 acyl group, —CO—NR 2a R 2a , —NR 2b CO—R 2a or —NR 2a R 2b (wherein R 2a and R 2b each independently designate a hydrogen atom or an optionally substituted C 1-6 alkyl group);
L designates a single bond, an optionally substituted C 1-6 alkylene group, an optionally substituted C 2-6 alkenylene group or an optionally substituted C 2-6 alkynylene group;
X designates a single bond, or a group represented by —NR 7 —, —O—, —CO—, —S—, —SO—, —SO 2 —, —CO—NR 8 -Z-, —C(O)O—, —NR 8 —CO-Z-, —NR 8 —C(O)O—, —NR 8 —S—, —NR 8 —SO—, —NR 8 —SO 2 -Z-, —NR 9 —CO—NR 10 —, —NR 9 —CS—NR 10 —, —S(O)—NR 11 -Z-, —C(═NR 12 )—NR 13 —, —OC(O)—, —OC(O)—NR 14 — or —CH 2 —NR 8 —COR 7 — (wherein R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 each independently designate a hydrogen atom, halogen atom, hydroxyl group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 2-6 alkenyloxy group, an optionally substituted C 1-6 alkylthio group, an optionally substituted C 2-6 alkenylthio group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group, Z designates a single bond or an optionally substituted C 1-6 alkylene group, and m designates 0, 1 or 2); and
Y designates any one group selected from the group consisting of a hydrogen atom, halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group or an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group, an optionally substituted 5- to 14-membered heteroaryl group, an optionally substituted amino group and a group represented by the formula —W—R 15 (wherein W designates CO or SO 2 ; and R 15 designates an optionally substituted C 1-6 alkyl group, an optionally substituted amino group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group).
21 . The compound according to claim 20 , a salt thereof or a hydrate of them, wherein at least one of R d , R e and R f is not a hydrogen atom.
22 . The compound according to claim 20 , a salt threof or a hydrate of them, wherein either one of R d , R e and R f is a halogen atom or an optionally substituted C 1-6 alkoxy group.
23 . The compound according to any one of claims 20 to 22 , a salt thereof or a hydrate of them, wherein at least one of R b and R c is not a hydrogen atom, and L is a single bond, an optionally substituted C 2-6 alkenylene group or an optionally substituted C 2-6 alkynylene group, provided that, when L is a single bond, the case where X is a single bond, and Y is an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkenyl group, an optionally substituted 4- to 14-membered non-aromatic heterocyclic group, an optionally substituted C 6-14 aryl group or an optionally substituted 5- to 14-membered heteroaryl group is excluded.
24 . The compound according to any one of claims 1 to 22 , a salt thereof or a hydrate of them, wherein at least either h or j is 1.
25 . The compound according to any one of claims 1 to 22 , a salt thereof or a hydrate of them, wherein h and j are 0, and k is 1.
26 . The compound according to any one of claims 1 to 19 , a salt thereof or a hydrate of them, wherein h, j and k are 0.
27 . The compound according to any one of claims 24 and 25 , a salt thereof or a hydrate of them, wherein R b and/or R c are(is) a hydrogen atom.
28 . The compound according to claim 27 , a salt thereof or a hydrate of them, wherein R b and R c are a hydrogen atom.
29 . The compound according to any one of claims 1 to 28 , a salt thereof or a hydrate of them, wherein Ar is a C 6-14 aryl group or a 5- to 14-membered heteroaryl group, and Ar is a group which may be substituted with 1 to 3 group(s) selected from the following substituent group (a):
<Substituent group a> the group consisting of (1) each optionally substituted (a) C 1-6 alkyl groups, (b) C 1-6 alkoxy groups, (c) C 1-7 acyl groups, (d) amide group, (e) amino group, (f) C 3-8 cycloalkyl groups, (2) halogen atom, (3) hydroxyl group, (4) nitro group, (5) cyano group, and (6) carboxyl group.
30 . The compound according to claim 29 , a salt thereof or a hydrate of them, wherein Ar is a phenyl group, naphthyl group or a 5- to 10-membered heteroaryl group, and Ar is a group optionally substituted with 1 to 3 group(s) selected from Substituent group A described in claim 29 .
31 . The compound according to claim 29 , a salt thereof or a hydrate of them, wherein Ar is a phenyl group, 2-naphthyl group, pyridyl group, 2-thienyl group, 2-furyl group, 2-benzofuryl group, 2-quinolyl group or 2-benzothienyl group, and Ar is a group optionally substituted with 1 to 3 group(s) selected from Substituent group A described in claim 29 .
32 . The compound according to claim 29 , a salt thereof or a hydrate of them, wherein Ar is a phenyl group, pyridyl group, 2-thienyl group or 2-furyl group, and Ar is a group optionally substituted with 1 to 3 group(s) selected from Substituent group A described in claim 29 .
33 . The compound according to claim 29 , a salt thereof or a hydrate of them, wherein Ar is a 2-naphthyl group, 2-benzofuryl group, 2-quinolyl group or 2-benzothienyl group, and Ar is a group optionally substituted with 1 to 3 group(s) selected from Substituent group a described in claim 29 .
34 . The compound according to any one of claims 29 to 33 , a salt thereof or a hydrate of them, wherein Substituent group A is the group consisting of (1) C 1-6 alkyl groups each optionally substituted with 1 to 3 group(s) selected from the group consisting of a halogen atom, hydroxyl group and cyano group, (2) C 1-6 alkoxy groups optionally substituted with 1 to 3 group(s) selected from the group consisting of a halogen atom, hydroxyl group and cyano group, (3) halogen atom, (4) hydroxyl group, (5) cyano group, and (6) C 1-7 acyl groups.
35 . The compound according to any one of claims 29 to 33 , a salt thereof or a hydrate of them, wherein Substituent group A is a halogen atom.
36 . The compound according to any one of claims 1 to 35 , a salt thereof or a hydrate of them, wherein L is a single bond or methylene group.
37 . The compound according to claim 36 , a salt thereof or a hydrate of them, wherein L is a single bond.
38 . The compound according to any one of claims 1 to 37 , a salt thereof or a hydrate of them, wherein X is a group represented by —CO—NR 8 -Z-, —NR 8 —CO-Z- or —NR 8 —SO 2 -Z- (wherein R 8 and Z have the same meanings as defined for R 8 and Z in claim 1) .
39 . The compound according to claim 38 , a salt thereof or a hydrate of them, wherein R 8 is a hydrogen atom.
40 . The compound according to claim 38 , a salt thereof or a hydrate of them, wherein X is a group represented by —CO—NH—(CH 2 ) t — (wherein t designates 0 or 1).
41 . The compound according to claim 38 , a salt thereof or a hydrate of them, wherein X is a group represented by —NH—CO—(CH 2 ) t — (wherein t designates 0 or 1).
42 . The compound according to any one of claims 1 to 37 , a salt thereof or a hydrate of them, wherein X is a single bond.
43 . The compound according to any one of claims 1 to 42 , a salt thereof or a hydrate of them, wherein Y is a C 1-6 alkyl group, a C 6-14 aryl group, a C 1-6 alkoxy group, a C 3-8 cycloalkyl group, a 4- to 14-membered non-aromatic heterocyclic group or a 5- to 14-membered heteroaryl group, and Y is a group optionally substituted with 1 to 3 group(s) selected from the following Substituent group a2:
<Substituent group a2> the group consisting of (1) each optionally substituted (a) C 1-6 alkyl groups, (b) C 2-6 alkenyl groups, (c) C 2-6 alkynyl groups, (d) C 1-6 alkoxy groups, (e) C 2-7 acyl groups, (f) amide group, (g) amino group, (h) C 3-8 cycloalkyl groups, (i) C 3-8 cycloalkenyl groups, (j) C 6-14 aryl groups, (k) 5 - to 14-membered heteroaryl groups, (1) C 6-14 aryloxy groups, and (m) 4- to 14-membered non-aromatic heterocyclic groups, (2) halogen atom, (3) hydroxyl group, (4) nitro group, (5) cyano group, and (6) carboxyl group.
44 . The compound according to claim 43 , a salt thereof or a hydrate of them, wherein Y is a C 3-8 cycloalkyl group, phenyl group, a 5- or 6-membered non-aromatic heterocyclic group, or a 5- or 6-membered heteroaryl group, and Y is a group optionally substituted with 1 to 3 group(s) selected from Substituent group a2 described in claim 43 .
45 . The compound according to any one of claims 1 to 42 , a salt thereof or a hydrate of them, wherein Y is a furyl group, thienyl group, pyrrolyl group, phenyl group, pyridyl group, C 3-8 cycloalkyl group, tetrahydrofuran-yl group, tetrahydrothiophene-yl group, pyrrolidinyl group, tetrahydrofuran-2-on-yl group, pyrrolidine-2-on-yl group or a group represented by the formula:
(wherein Y 2a designates a group represented by —CONH 2 or —CH 2 OH, Y 2b and Y 2c each independently designate a hydrogen atom, an optionally substituted phenyl group or an optionally substituted C 1-6 alkyl group), and Y is a group optionally substituted with 1 to 3 group(s) selected from Substituent group a2 described in claim 43 .
46 . The compound according to claim 43 , a salt thereof or a hydrate of them, wherein Y is a furyl group or thienyl group, and Y is a group optionally substituted with 1 to 3 group(s) selected from Substituent group a2 described in claim 43 .
47 . The compound according to any one of claims 43 to 46 , a salt thereof or a hydrate of them, wherein Substituent group a2 is the group consisting of (1) (a) C 1-6 alkyl groups, (b) C 1-6 alkoxy groups, (C)C 1-7 acyl groups, (d) amide group, (e) amino group, (f) C 3-8 cycloalkyl groups, each of which may be substituted with 1 to 3 group(s) selected from the following Substituent group b2, (2) halogen atom, (3) hydroxyl group, (4) nitro group, (5) cyano group, and (6) carboxyl group, and <Substituent group b2> is the group consisting of C 1-6 alkyl groups, halogen atom, hydroxyl group, nitro group, cyano group and carboxyl group.
48 . The compound according to any one of claims 43 to 46 , a salt thereof or a hydrate of them, wherein Substituent group a2 is the group consisting of (1) C 1-6 alkoxy groups, (2) halogen atoms and (3) cyano groups.
49 . The compound according to any one of claims 20 to 35 , a salt thereof or a hydrate of them, wherein L and X are a single bond, Y is a 5- to 6-membered heteroaryl group, and Y is a group optionally substituted with 1 to 3 group(s) selected from Substituent group a2 described in claim 43 .
50 . A pharmaceutical composition comprising the compound according to anyone of claims 1 to 49 , a salt thereof or a hydrate of them, and a pharmaceutically acceptable carrier.
51 . A c-Jun amino-terminal kinase (JNKs) inhibitor comprising the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them.
52 . A c-Jun amino-terminal kinase 1 (JNK 1), c-Jun amino-terminal kinase 2 (JNK 2) and/or c-Jun amino-terminal kinase 3 (JNK 3) inhibitor, comprising the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them.
53 . An agent for treating or preventing immunological diseases, inflammatory diseases or metabolic disorders, which comprises the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them.
54 . An agent for treating or preventing neurodegenerative diseases, which comprises the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them.
55 . An agent for treating or preventing Alzheimer's disease, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis, multiple sclerosis or spinocerebellar degeneration, which comprises the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them.
56 . Use of the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them for prevention or treatment of immunological diseases, inflammatory diseases, metabolic disorders and/or neurodegenerative diseases.
57 . Use of the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them, for producing an agent for treating or preventing a disease based on JNK action against which inhibition of a c-Jun amino-terminal kinase (JNK) is effective for prevention or treatment, immunological diseases, inflammatory diseases, metablic disorders or neurodegenerative diseases.
58 . The use according to claim 57 , wherein the disease is Alzheimer's disease, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis, multiple sclerosis or spinocerebellar degeneration.
59 . A method for treating or preventing a disease based on JNK 3 action against which inhibition of a c-Jun amino-terminal kinase 3 (JNK 3) is effective for prevention or treatment, immunological diseases, inflammatory diseases, metablic disorders and/or neurodegenerative diseases, which comprises adiministering a pharmacologically effective amount of the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them to a patient.
60 . A method for treating or preventing a disease based on JNK action against which inhibition of a c-Jun amino-terminal kinase (JNK) is effective for prevention or treatment, immunological diseases, inflammatory diseases, metablic disorders or neurodegenerative diseases, which comprises adiministering a pharmacologically effective amount of the compound according to any one of claims 1 to 49 , a salt thereof or a hydrate of them to a patient.
61 . The method according to claim 60 , wherein the disease is Alzheimer's disease, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis, multiple sclerosis or spinocerebellar degeneration.