1. A compound of formula (I) or a salt thereof
[Chem 1]
( I )
[wherein,
R
1
are the same or different from each other, and are C1-6 alkyl, halogeno-C1-6 alkyl,
C3-8 cycloalkyl, halogen, -O-C1-6 alkyl, -O-halogeno-C1-6 alkyl or cyano,
R
2
is C1-6 alkyl, C3-8 cycloalkyl, halogeno-C1-6 alkyl, -O-C1-6 alkyl, -N(C1-6 alkyl)2 or
aryl,
R
3
is H or C1-6 alkyl,
R
4
is C1-6 alkyl substituted with the same or different one to four R5
, -C1-6 alkylene-
(aryl optionally substituted with the same or different one to four R6
), -C1-6 alkylene-(C3-
8 cycloalkyl optionally substituted with the same or different one to four R7
), -C1-6 alkylene-
(heteroaryl optionally substituted with the same or different one to four R8
), -C1-6 alkylene-
(4 to 7-membered saturated heterocyclyl optionally substituted with the same or different one
to four R9
), C3-8 cycloalkyl optionally substituted with the same or different one to four R10
,
heteroaryl optionally substituted with the same or different one to four R11, or a 4 to 8-
membered saturated heterocyclyl optionally substituted with the same or different one to four
R
12
,
R
5
is -OR13
, -NR14R
15, halogen or cyano,
R
6
is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-6 alkyleneOR13
, -C1-6 alkylene-NR14R
15, halogen or cyano,
R
7
is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-6 alkyleneWE CLAIM:
105
OR13
, -C1-6 alkylene-NR14R
15, halogen or cyano,
R
8
is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-6 alkyleneOR13
, -C1-6 alkylene-NR14R
15, halogen or cyano,
R
9
is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-6 alkyleneOR13
, -C1-6 alkylene-NR14R
15, halogen, cyano, oxo, -C(O)-C1-6 alkyl or -S(O)2-C1-6 alkyl,
R
10
is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-
6 alkylene-OR13
, -C1-6 alkylene-NR14R
15, halogen, -C(O)-OH or cyano,
R
11
is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-
6 alkylene-OR13
, -C1-6 alkylene-NR14R
15, halogen or cyano,
R
12 is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, 4 to 7-membered saturated
heterocyclyl, -OR13
, -NR14R
15
, -C1-6 alkylene-C3-8 cycloalkyl, -C1-6 alkylene-OR13
, -C1-
6 alkylene-NR14R
15
, -C1-6 alkylene-cyano, -C1-6 alkylene-C(O)-OH, halogen, cyano, oxo, -
C(O)-NH2, -C(O)-C1-6 alkyl or -S(O)2-C1-6 alkyl,
R
13
is H or C1-6 alkyl,
R
14
and R15 are the same or different from each other, and are H, C1-6 alkyl or -C(O)-
C1-6 alkyl, and
n is an integer of 1 to 4, which represents the number of R1
substituents].
2. The compound or a salt thereof according to claim 1, wherein R4
is C1-6 alkyl
substituted with the same or different one to four R5
; -C1-6 alkylene-(aryl optionally
substituted with the same or different one to four R6
); -C1-6 alkylene-(C3-8 cycloalkyl
optionally substituted with the same or different one to four R7
), -C1-6 alkylene-(heteroaryl
optionally substituted with the same or different one to four R8
); -C1-6 alkylene-(4 to 7-
membered saturated heterocyclyl optionally substituted with the same or different one to four
R
9
); C3-8 cycloalkyl optionally substituted with the same or different one to four R10;
heteroaryl optionally substituted with the same or different one to four R11; or 4 to 7-
membered saturated heterocyclyl optionally substituted with the same or different one to four
R
12;
R
10 is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-
106
6 alkylene-OR13
, -C1-6 alkylene-NR14R
15, halogen or cyano; and
R
12 is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-
6 alkylene-OR13
, -C1-6 alkylene-NR14R
15, halogen, cyano, oxo, -C(O)-C1-6 alkyl or -S(O)2-C1-
6 alkyl.
3. The compound or a salt thereof according to claim 2, wherein the formula (I) is
formula (Ia).
[Chem 2]
( )k
( Ia )
[wherein,
R
1a is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, halogen, -O-C1-6 alkyl, -Ohalogeno-C1-6 alkyl or cyano,
R
1b are the same or different from each other, and are C1-6 alkyl, halogeno-C1-6 alkyl
or halogen,
R
2
is C1-6 alkyl, C3-8 cycloalkyl, halogeno-C1-6 alkyl, -N(C1-6 alkyl)2 or aryl,
R
3
is H,
R
4
is C1-6 alkyl substituted with the same or different one to four R5
, -C1-6 alkylene-
(aryl optionally substituted with the same or different one to four R6
), -C1-6 alkylene-(C3-
8 cycloalkyl optionally substituted with the same or different one to four R7
), -C1-6 alkyleneheteroaryl, -C1-6 alkylene-(4 to 7-membered saturated heterocyclyl optionally substituted with
the same or different one to four R9
), C3-8 cycloalkyl optionally substituted with the same or
different one to four R10, heteroaryl or 4 to 7-membered saturated heterocyclyl optionally
substituted with the same or different one to four R
12
,
R
5
is -OR13
, -NR14R
15, halogen or cyano,
R
6
is -OR13
,
107
R
7
is -OR13
, -NR14R
15
, -C1-6 alkylene-OR13
or -C1-6 alkylene-NR14R
15
,
R
9
is -C(O)-C1-6 alkyl,
R
10
is C1-6 alkyl, -OR13
, -NR14R
15
, -C1-6 alkylene-OR13
, -C1-6 alkylene-NR14R
15
,
halogen or cyano,
R
12
is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, -OR13
, -NR14R
15
, -C1-
6 alkylene-OR13
, -C1-6 alkylene-NR14R
15, halogen, cyano, oxo, -C(O)-C1-6 alkyl or -S(O)2-C1-
6 alkyl,
R
13
is H or C1-6 alkyl,
R
14
and R15 are the same or different from each other, and are H, C1-6 alkyl or -C(O)-
C1-6 alkyl, and
k is 0 or 1, which represents the number of R1b substituents].
4. The compound or a salt thereof according to claim 3, wherein
R
1a is C1-6 alkyl, halogeno-C1-6 alkyl, C3-8 cycloalkyl, halogen, -O-C1-6 alkyl or -Ohalogeno-C1-6 alkyl,
R
2
is C1-6 alkyl or C3-8 cycloalkyl,
R
4
is -C1-6 alkylene-(C3-8 cycloalkyl optionally substituted with the same or different
one to four R7
), -C1-6 alkylene-(4 to 7-membered saturated heterocyclyl optionally substituted
with the same or different one to four R9
), C3-8 cycloalkyl optionally substituted with the
same or different one to four R10, or a 4 to 7-membered saturated heterocyclyl optionally
substituted with the same or different one to four R
12, and
k represents 0.
5. The compound or a salt thereof according to claim 1, wherein the compound is
selected from the group consisting of
2-(3-{[(1R,2R)-2-hydroxycyclohexyl]amino}-5-methyl-1,2,4-triazin-6-yl)-5-
(trifluoromethoxy)phenol,
(3S,4R)-4-{[6-(4-chloro-2-hydroxyphenyl)-5-methyl-1,2,4-triazin-3-yl]amino}oxan3-ol,
2-(5-cyclopropyl-3-{[(1s,3s)-3-hydroxy-3-methylcyclobutyl]amino}-1,2,4-triazin-6-
108
yl)-5-(trifluoromethyl)phenol,
2-(3-{[(1R,2R)-2-hydroxycyclohexyl]amino}-5-methyl-1,2,4-triazin-6-yl)-5-
methoxyphenol,
2-(3-{[(3R)-1-cyclopropylpiperidin-3-yl]amino}-5-methyl-1,2,4-triazin-6-yl)-5-
(trifluoromethyl)phenol,
2-(3-{[(1R,3S)-3-hydroxycyclohexyl]amino}-5-methyl-1,2,4-triazin-6-yl)-5-
(trifluoromethyl)phenol,
5-(difluoromethoxy)-2-(3-{[(1R,2R)-2-hydroxycyclohexyl]amino}-5-methyl-1,2,4-
triazin-6-yl)phenol,
2-(3-{[(1R,2R)-2-aminocyclohexyl]amino}-5-methyl-1,2,4-triazin-6-yl)-5-
(trifluoromethyl)phenol,
2-[5-methyl-3-({[(2R)-morpholin-2-yl]methyl}amino)-1,2,4-triazin-6-yl]-5-
(trifluoromethyl)phenol,
2-(5-methyl-3-{[(3R)-1-methylpiperidin-3-yl]amino}-1,2,4-triazin-6-yl)-5-
(trifluoromethyl)phenol, and
5-(difluoromethoxy)-2-(5-methyl-3-{[(3R)-1-methylpiperidin-3-yl]amino}-1,2,4-
triazin-6-yl)phenol.
6. The compound or a salt thereof according to claim 1, wherein the compound is
selected from the group consisting of
2-(3-{[(1R,2R)-2-hydroxycyclohexyl]amino}-5-methyl-1,2,4-triazin-6-yl)-5-
methoxyphenol monohydrochloride,
2-(3-{[(1R,3S)-3-hydroxycyclohexyl]amino}-5-methyl-1,2,4-triazin-6-yl)-5-
(trifluoromethyl)phenol monohydrochloride,
5-(difluoromethoxy)-2-(3-{[(1R,2R)-2-hydroxycyclohexyl]amino}-5-methyl-1,2,4-
triazin-6-yl)phenol monohydrochloride,
2-(5-methyl-3-{[(3R)-1-methylpiperidin-3-yl]amino}-1,2,4-triazin-6-yl)-5-
(trifluoromethyl)phenol dihydrochloride, and
2-(3-{[(1R,2R)-2-aminocyclohexyl]amino}-5-methyl-1,2,4-triazin-6-yl)-5-
109
(trifluoromethyl)phenol dihydrochloride.
7. A pharmaceutical composition comprising the compound or a salt thereof according
to claim 1 and one or more pharmaceutically acceptable excipients.
8. The pharmaceutical composition according to claim 7, which is an
NLRP3 inflammasome activation inhibitor.
9. The pharmaceutical composition according to claim 7, which is a pharmaceutical
composition for preventing and/or treating an inflammatory disease and/or a
neurodegenerative disease.
10. Use of the compound or a salt thereof according to claim 1, for the manufacture of a
pharmaceutical composition for preventing and/or treating an inflammatory disease and/or a
neurodegenerative disease