US2009312313A1PendingUtilityA1
Compound having tgfbeta inhibitory activity and pharmaceutical composition comprising the same
Est. expiryAug 23, 2022(expired)· nominal 20-yr term from priority
A61P 41/00A61P 43/00A61P 9/00A61P 9/10A61P 35/00A61P 3/10A61P 27/02A61P 11/00A61P 17/00A61P 19/04A61P 13/12A61P 17/02C07D 401/14A61P 1/04A61P 1/16C07D 215/233A61P 19/02A61K 31/47
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Claims
Abstract
The present invention provides compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: wherein X represents CH or N; Z represents —O—, —NH— or —C(═O)—; R and R′ represent a hydrogen atom, hydroxyl, a halogen atom, optionally substituted alkyl, optionally substituted alkenyl optionally substituted alkoxy, amino, aminocarbonyl, or an optionally substituted heterocyclic group; and A represents an optionally substituted specific carbocyclic or heterocyclic group. The compounds according to the present invention have excellent TGFβ inhibitory activity.
Claims
exact text as granted — not AI-modified1 . A compound represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof:
wherein
X represents or N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R and R′, which may be the same or different, represent
1) a hydrogen atom,
2) a halogen atom, or
3) C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, or
a saturated or unsaturated five- or six-membered heterocyclic group,
4) C 2-6 alkenyl optionally substituted by an oxygen atom or C 1-4 alkoxy,
5) amino in which one or two hydrogen atoms on the amino group are optionally substituted by C 1-6 alkyl, and the C 1-6 alkyl group is optionally substituted by hydroxyl or a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group,
6) —C(═O)—NH 2 wherein one or two hydrogen atoms on the aminocarbonyl group are optionally substituted by C 1-6 alkyl,
7) —OR″ wherein R″ represents a hydrogen atom, or —(CH 2 ) m —R a wherein R a represents a hydrogen atom, a halogen atom, hydroxyl, a saturated or unsaturated three- to six-membered carbocyclic or heterocyclic group, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or —NR b R c wherein R b and R c , which may be the same or different, represent a hydrogen atom or C 1-6 alkyl, in which the C 1-6 alkyl group is optionally substituted by hydroxyl, an oxygen atom, amino, a nitrogen atom, or C 1-4 alkyl, and R b and R c may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group, which may further comprise one or more heteroatoms, and in which the heterocyclic group is optionally substituted by C 1-4 alkyl optionally substituted by hydroxyl, hydroxyl, an oxygen atom, aminocarbonyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group; m is an integer of 1 to 6; and the alkyl chain part in this group, —(CH 2 ) m —, is optionally substituted by hydroxyl, an oxygen atom, —OR d group, wherein R d represents C 1-4 alkyl or C 1-4 alkylcarbonyl, or C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom, or
8) a saturated or unsaturated five- or six-membered heterocyclic group, and
A represents any group selected from the group consisting of formulae (a) to (c):
(a) a group of formula (a):
wherein
R 3 to R 6 , which may be the same or different, represent
a hydrogen atom,
hydroxyl,
a halogen atom,
C 1-6 alkyl,
C 1-10 alkoxy optionally substituted by a halogen atom or phenyl,
C 2-6 alkenylcarbonyloxy,
C 1-4 alkylcarbonyl,
C 1-4 alkylthio, or
phenyl optionally substituted by a halogen atom,
R 3 and R 4 , R 4 and R 5 , and R 5 and R 6 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a hydrogen atom, a halogen atom, hydroxyl, or C 1-4 alkyl,
G represents
—C(═O)—R 7 ,
—CH 2 —N(—R 11 )R 12 , or
—C(—R 13 )(═NR 14 ),
wherein
R 7 represents
a hydrogen atom,
C 1-8 alkyl optionally substituted by C 1-4 alkoxy, an oxygen atom, or a saturated or unsaturated five- or six-membered carbocyclic group,
C 2-6 alkenyl optionally substituted by a saturated or unsaturated five- or six-membered carbocyclic group,
a saturated or unsaturated five- or six-membered carbocyclic group or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by hydroxyl, C 1-4 alkyl, or C 1-4 alkoxy, and the C 1-4 alkoxy group is optionally substituted by a halogen atom or a saturated or unsaturated five- or six-membered heterocyclic group,
group —O—R 8 , or
group —N(—R 9 )R 10
wherein
R 8 represents
C 1-10 alkyl optionally substituted by a saturated or unsaturated five- or six-membered carbocyclic group,
C 2-8 alkenyl, or
a saturated or unsaturated five- or six-membered carbocyclic group in which the carbocyclic group is optionally substituted by a halogen atom,
R 9 and R 10 , and R 11 and R 12 , which may be the same or different, each represent
a hydrogen atom,
C 1-6 alkyl,
a saturated or unsaturated five- or six-membered carbocyclic group in which the carbocyclic group is optionally substituted by a halogen atom, or
naphthyl optionally substituted by a halogen atom,
R 9 and R 10 , or R 11 and R 12 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl optionally substituted by hydroxyl, or a saturated or unsaturated five- or six-membered heterocyclic group,
R 13 represents
a hydrogen atom or
C 1-4 alkyl,
R 14 represents
a hydrogen atom,
hydroxyl,
C 1-4 alkoxy optionally substituted by a saturated or unsaturated six-membered carbocyclic group,
C 2-6 alkenyloxy,
phenyloxy, or
amino optionally substituted by a saturated or unsaturated six-membered heterocyclic group,
(b) a group of formula (b):
wherein
any one of J, L, and M represents a nitrogen atom with the remaining two representing a carbon atom,
R 15 to R 19 , which may be the same or different, represent
a hydrogen atom,
a halogen atom,
nitro,
cyano,
C 1-6 alkyl in which the alkyl group is optionally substituted by hydroxyl; phenyl; amino optionally substituted by C 1-4 alkyl; C 1-4 alkylcarbonyloxy; or a saturated or unsaturated six-membered heterocyclic group optionally substituted by C 1-4 alkyl,
C 1-8 alkoxy,
C 1-4 alkylcarbonyl,
C 2-6 alkenyl optionally substituted by a saturated or unsaturated five- or six-membered carbocyclic group,
C 2-6 alkynyl optionally substituted by C 1-4 alkylsilyl,
C 1-4 alkylthio,
a saturated or unsaturated three- to eight-membered carbocyclic oxy group,
a saturated or unsaturated six-membered carbocyclic carbonyl or heterocyclic carbonyl group optionally substituted by C 1-4 alkyl, or
a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by hydroxyl; cyano; a halogen atom; C 1-4 alkoxy; phenyloxy; C 1-4 alkylcarbonyl; amino optionally substituted by C 1-4 alkyl or C 1-4 alkylcarbonyl; aminocarbonyl optionally substituted by C 1-4 alkyl; or C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom,
R 15 and R 16 , R 16 and R 17 , R 17 and R 18 , and R 18 and R 19 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group, and the carbocyclic or heterocyclic group is optionally substituted by C 1-4 alkyl,
provided that, among R 17 to R 19 , those in which J, L, or M attached thereto is a nitrogen atom are absent, and
(c) a group of formula (c):
wherein
R 20 to R 24 , which may be the same or different, represent
a hydrogen atom,
a halogen atom,
C 1-10 alkyl optionally substituted by hydroxyl, a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group,
C 1-8 alkoxy,
C 2-6 alkenyl optionally substituted by C 1-4 alkyl, C 1-4 alkoxy, an oxygen atom or phenyl,
phenylcarbonyl optionally substituted by C 1-4 alkyl,
amino optionally substituted by phenyl,
nitro, or
a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by C 1-6 alkyl,
R 20 and R 21 , or R 23 and R 24 may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group, and
R 21 and R 22 , or R 22 and R 23 may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a halogen atom, C 1-4 alkyl, C 1-4 alkylcarbonyl, C 1-6 alkoxycarbonyl, or an oxygen atom, and the carbocyclic or heterocyclic group may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a tricyclic group together with the six-membered carbocyclic ring of formula (c).
2 . The compound according to claim 1 , represented by formula (II), or a pharmaceutically acceptable salt or solvate thereof:
wherein
X, Z, and A are as defined in claim 1 ,
R 1 and R 2 , which may be the same or different, represent a hydrogen atom, or —(CH 2 ) m —R a wherein R a represents a hydrogen atom, a halogen atom, hydroxyl, a saturated or unsaturated three- to six-membered carbocyclic or heterocyclic group, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or —NR b R c wherein R b and R c , which may be the same or different, represent a hydrogen atom or C 1-6 alkyl, in which the C 1-6 alkyl group is optionally substituted by hydroxyl, an oxygen atom, amino, a nitrogen atom, or C 1-4 alkyl, and R b and R c may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group, which may further comprise one or more heteroatoms, and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, hydroxyl, an oxygen atom, aminocarbonyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group; m is an integer of 1 to 6; and the alkyl chain part in this group, —(CH 2 ) m —, is optionally substituted by hydroxyl, an oxygen atom, —OR d group, wherein R d represents C 1-4 alkyl or C 1-4 alkylcarbonyl, or C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom.
3 . The compound according to claim 2 , wherein
R 1 and R 2 , which may be the same or different, represent any group selected from the group consisting of a hydrogen atom, C 1-6 alkyl optionally substituted by phenyl, and groups of formulae (i) to (vi): (i) a group of formula (i):
wherein
R 51 and R 52 , which may be the same or different, represent
a hydrogen atom, or
C 1-8 alkyl optionally substituted by hydroxyl, an oxygen atom, amino, or a nitrogen atom,
R 51 and R 52 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms, and in which the heterocyclic group is optionally substituted by C 1-4 alkyl optionally substituted by hydroxyl, hydroxyl, an oxygen atom, aminocarbonyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 51 to combine with R 52 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
p is an integer of 2 to 4, and
the alkyl chain part in this group is optionally substituted by hydroxyl, or —OR e group wherein R e represents C 1-4 alkyl or C 1-4 alkylcarbonyl,
(ii) a group of formula (ii):
wherein q is an integer of 1 to 4,
(iii) a group of formula (iii):
wherein Hal represents a halogen atom, and
r represents an integer of 2 to 4,
(iv) a group of formula (iv):
wherein
R 53 and R 54 , which may be the same or different, represent
a hydrogen atom, or
C 1-6 alkyl optionally substituted by hydroxyl,
R 53 and R 54 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl optionally substituted by hydroxyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 53 to combine with R 54 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group, and
s is an integer of 0 to 3,
(v) a group of formula (v):
wherein
R 55 represents C 1-4 alkyl and
t is an integer of 0 (zero) to 3, and
(vi) a group of formula (vi):
wherein
R 56 , R 57 and R 58 , which may be the same or different, represent
a hydrogen atom,
C 1-4 alkoxycarbonyl, or
C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom, and
u is an integer of 0 (zero) to 4.
4 . The compound according to claim 3 , wherein formula (i) is represented by formula (i-a):
5 . The compound according to claim 3 or 4 , wherein
R 1 and R 2 , which may be the same or different, represent any group selected from the group consisting of a hydrogen atom, C 1-6 alkyl, benzyl, groups of formulae (i), (v), and (vi) according to claim 3 , and groups of formulae (ii-a), (iii-a), and (iv-a):
formula (ii-a):
formula (iii-a):
wherein r1 is an integer of 2 to 4, and
formula (iv-a):
6 . The compound according to claim 5 , wherein one of R 1 and R 2 is selected from C 1-6 alkyl, and the other substituent is selected from the group consisting of
a hydrogen atom, benzyl, groups of formulae (i), (v), and (vi) according to claim 3 , and groups of formulae (ii-a), (iii-a), and (iv-a) according to claim 5 .
7 . The compound according to claim 1 , wherein
at least one of R and R′ is selected from the group consisting of a hydrogen atom, a halogen atom, C 1-4 alkyl optionally substituted by hydroxyl, a halogen atom, or a saturated or unsaturated five- or six-membered heterocyclic group, C 2-4 alkenyl optionally substituted by an oxygen atom or C 1-4 alkoxy, amino in which one or two hydrogen atoms on the amino group are optionally substituted by C 1-4 alkyl, and the C 1-4 alkyl group is optionally substituted by hydroxyl or a saturated or unsaturated five- or six-membered heterocyclic group, —C(═O)—NH 2 , and a saturated or unsaturated five- or six-membered heterocyclic group.
8 . The compound according to claim 1 , wherein
R′ is selected from the group consisting of a hydrogen atom, a halogen atom, C 1-4 alkyl optionally substituted by hydroxyl, a halogen atom, or a saturated or unsaturated five- or six-membered heterocyclic group, C 2-4 alkenyl optionally substituted by an oxygen atom or C 1-4 alkoxy, amino in which one or two hydrogen atoms on the amino group are optionally substituted by C 1-4 alkyl, and the C 1-4 alkyl group is optionally substituted by hydroxyl or a saturated or unsaturated five- or six-membered heterocyclic group, —C(═O)—NH 2 , and a saturated or unsaturated five- or six-membered heterocyclic group.
9 . The compound according to claim 1 , wherein formula (a), which A may represent, represents any group selected from the group consisting of formulae (a1) to (a3):
(1) a group of formula (a1):
wherein
R 3 , R 4 and R 6 , which may be the same or different, represent
a hydrogen atom,
a halogen atom,
C 1-6 alkyl,
C 1-10 alkoxy optionally substituted by a halogen atom or phenyl,
C 2-6 alkenylcarbonyloxy,
C 1-4 alkylcarbonyl, or
phenyl optionally substituted by a halogen atom,
R 5 is as defined in claim 1 ,
R 3 and R 4 , R 4 and R 5 , and R 5 and R 6 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group, and
R 7 is as defined in claim 1 ,
(2) a group of formula (a2):
wherein
R 3 to R 6 are as defined in formula (a1),
R 11 and R 12 are as defined in claim 1 , and
(3) a group of formula (a3):
wherein
R 3a to R 6a , which may be the same or different, represent
a hydrogen atom,
a halogen atom, or
C 1-6 alkyl, and
R 13 and R 14 are as defined in claim 1 .
10 . The compound according to claim 9 , wherein A represents a group of formula (a1) and at least one of R 3 to R 6 in formula (a1) is selected from groups other than a hydrogen atom.
11 . The compound according to claim 9 or 10 , wherein A represents a group of formula (a1) and R 7 in formula (a1) represents a hydrogen atom, C 1-4 alkyl, or phenyl in which the phenyl group is optionally substituted by hydroxyl, C 1-4 alkyl, or C 1-4 alkoxy.
12 . The compound according to claim 9 or 10 , wherein A represents a group of formula (a1) and R 7 in formula (a1) represents group —O—R 8 or group —N(—R 9 )R 10 .
13 . The compound according to claim 12 , wherein R 8 represents unsubstituted C 1-8 alkyl; C 1-4 alkyl substituted by phenyl; C 2-8 alkenyl; or phenyl optionally substituted by a halogen atom.
14 . The compound according to claim 12 , wherein
at least one of R 9 and R 10 represents a hydrogen atom and the other substituent represents a hydrogen atom, C 1-6 alkyl, a saturated or unsaturated five- or six-membered carbocyclic group in which the carbocyclic group is optionally substituted by a halogen atom, or naphthyl optionally substituted by a halogen atom, or R 9 and R 10 combine with a nitrogen atom attached thereto to form a saturated five- or six-membered heterocyclic group in which the heterocyclic group may further comprise at least one heteroatom.
15 . The compound according to claim 9 , wherein A represents a group of formula (a1) and R 5 in formula (a1) is selected from groups other than a hydrogen atom.
16 . The compound according to claim 10 , wherein R and R′ are selected from —OR″ wherein R″ represents C 1-6 alkyl.
17 . The compound according to claim 9 , wherein A represents a group of formula (a2) and R 11 and R 12 in formula (a2) combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group in which the heterocyclic group may further comprise one or more heteroatoms and is optionally substituted by C 1-4 alkyl optionally substituted by hydroxyl; or a saturated five- or six-membered heterocyclic group.
18 . The compound according to claim 17 , wherein A represents a group of formula (a2) and, in formula (a2),
R 3 , R 4 , and R 6 represent a hydrogen atom, hydroxyl, or a halogen atom, and R 5 represents C 1-4 alkyl.
19 . The compound according to claim 9 , wherein
A represents a group of formula (a3) and, in formula (a3), R 13 represents methyl, and R 14 represents hydroxyl; C 1-4 alkoxy optionally substituted by phenyl; C 2-6 alkenyloxy; phenyloxy; or amino optionally substituted by a six-membered unsaturated heterocyclic group.
20 . The compound according to claim 9 or 19 , wherein A represents a group of formula (a3), and, in formula (a3),
R 3a and R 6a represents a hydrogen atom, and R 4a and R 5a represent C 1-6 alkyl.
21 . The compound according to claim 1 , wherein A is selected from groups of formula (a) or (b).
22 . The compound according to claim 1 , wherein formula (b), which A may represent, represents any group selected from the group consisting of formulae (b1) to (b3):
(4) a group of formula (b1):
wherein
R 25 to R 27 , which may be the same or different, represent
a hydrogen atom,
a halogen atom,
C 1-6 alkyl,
C 1-8 alkoxy,
C 1-4 alkylcarbonyl,
C 1-4 alkylthio, or
phenylcarbonyl,
R 25 and R 26 , and R 26 and R 27 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group,
R 28 represents
a hydrogen atom,
a halogen atom,
nitro,
cyano,
C 1-6 alkyl in which the alkyl group is optionally substituted by hydroxyl; phenyl; amino optionally substituted by C 1-4 alkyl; C 1-4 alkylcarbonyloxy; or a saturated or unsaturated six-membered heterocyclic group optionally substituted by C 1-4 alkyl,
C 1-8 alkoxy,
C 1-4 alkylcarbonyl,
C 2-6 alkenyl optionally substituted by a saturated or unsaturated six-membered carbocyclic group,
C 2-6 alkynyl optionally substituted by C 1-2 alkylsilyl,
a saturated or unsaturated three- to eight-membered carbocyclic oxy group,
a saturated or unsaturated six-membered carbocyclic carbonyl or heterocyclic carbonyl group optionally substituted by C 1-4 alkyl, or
a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by hydroxyl; cyano; a halogen atom; C 1-4 alkoxy; phenyloxy; C 1-4 alkylcarbonyl; amino optionally substituted by C 1-4 alkyl or C 1-4 alkylcarbonyl; aminocarbonyl optionally substituted by C 1-4 alkyl; or C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom,
(5) a group of formula (b2):
wherein
R 29 to R 32 , which may be the same or different, represent
a hydrogen atom,
a halogen atom, or
C 1-6 alkyl optionally substituted by hydroxyl,
R 29 and R 30 , and R 31 and R 32 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a halogen atom or C 1-4 alkyl, and
(6) a group of formula (b3):
wherein
R 33 to R 36 , which may be the same or different, represent
a hydrogen atom,
a halogen atom, or
C 1-6 alkyl optionally substituted by hydroxyl,
R 33 and R 34 , R 34 and R 35 , and R 35 and R 36 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a halogen atom or C 1-4 alkyl.
23 . The compound according to claim 22 , wherein A represents a group of formula (b1) and, in formula (b1),
R 25 represents a hydrogen atom, R 26 represents a hydrogen atom, a halogen atom, or C 1-4 alkyl, R 27 represents a hydrogen atom, a halogen atom, C 1-4 alkyl, C 1-4 alkoxy, or C 1-4 alkylthio, and R 26 and R 27 may combine with a carbon atom attached thereto to form an unsaturated six-membered carbocyclic or heterocyclic group.
24 . The compound according to claim 1 , wherein
A represents a group of formula (b1) and, in formula (b1), R 25 represents a hydrogen atom, R 26 represents a hydrogen atom, a halogen atom, or C 1-4 alkyl, R 27 represents a hydrogen atom, a halogen atom, C 1-4 alkyl, C 1-4 alkoxy, or C 1-4 alkylthio, R 26 and R 27 may combine with a carbon atom attached thereto to form an unsaturated six-membered carbocyclic or heterocyclic group, and R 28 represents a saturated or unsaturated four- to seven-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by hydroxyl; cyano; a halogen atom; C 1-4 alkoxy; phenyloxy; C 1-4 alkylcarbonyl; amino optionally substituted by C 1-4 alkyl or C 1-4 alkylcarbonyl; aminocarbonyl optionally substituted by C 1-4 alkyl; or C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom.
25 . The compound according to claim 22 , wherein A represents a group of formula (b2) and, in formula (b2),
R 29 represents a hydrogen atom, R 30 represents a hydrogen atom or C 1-4 alkyl, and R 31 and R 32 combine with carbon atom attached thereto to from an unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a halogen atom or C 1-4 alkyl.
26 . The compound according to claim 22 , wherein A represents a group of formula (b3) and, in formula (b3),
R 33 and R 34 represent a hydrogen atom, and
R 35 and R 36 combine with a carbon atom attached thereto to form an unsaturated five- or six-membered carbocyclic or heterocyclic group.
27 . The compound according to claim 1 , wherein when one of R 1 and R 2 is selected from C 1-6 alkyl, and the other substituent is selected from the group consisting of
a hydrogen atom, benzyl, groups of formulae (i), (v), and (vi) according to claim 3 , and groups of formulae (ii-a), (iii-a), and (iv-a) according to claim 5 , A is selected from groups of formula (b1).
28 . The compound according to claim 1 , wherein A represents a group of formula (c) and, in formula (c),
R 21 and R 22 , or R 22 and R 23 combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a halogen atom, C 1-4 alkyl, C 1-4 alkylcarbonyl, C 1-6 alkoxycarbonyl, or an oxygen atom and may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form, together with the six-membered carbocyclic ring in formula (c), a tricyclic group, and any one of or both R 20 and R 24 is selected from groups other than a hydrogen atom.
29 . The compound according to claim 1 or pharmaceutically acceptable salt or solvate thereof, wherein formula (I) is represented by formula (100):
wherein
X represents CH or N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R 101 and R 102 , which may be the same or different, represent any group selected from the group consisting of
a hydrogen atom,
C 1-6 alkyl,
benzyl, and
groups of formulae (i), (ii-a), (iii-a), (iv-a), (v), and (vi),
(i) a group of formula (i):
wherein
R 51 and R 52 , which may be the same or different, represent
a hydrogen atom, or
C 1-8 alkyl optionally substituted by hydroxyl, an oxygen atom, amino, or a nitrogen atom,
R 51 and R 52 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, hydroxyl, an oxygen atom, aminocarbonyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 51 to combine with R 52 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
p is an integer of 2 to 4, and
the alkyl chain part in this group is optionally substituted by hydroxyl, or —OR e group wherein R e represents C 1-4 alkyl or C 1-4 alkylcarbonyl,
(ii) a group of formula (ii-a):
(iii) a group of formula (iii-a):
wherein r1 represents an integer of 2 to 4,
(iv) a group of formula (iv-a):
wherein
R 53 and R 54 , which may be the same or different, represent
a hydrogen atom, or
C 1-6 alkyl optionally substituted by hydroxyl, and
R 53 and R 54 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 53 to combine with R 54 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
(v) a group of formula (v):
wherein
R 55 represents C 1-4 alkyl and
t is an integer of 0 (zero) to 3, and
(vi) a group of formula (vi):
wherein
R 56 , R 57 and R 58 , which may be the same or different, represent
a hydrogen atom,
C 1-4 alkoxycarbonyl, or
C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom, and
u is an integer of 0 (zero) to 4,
R 103 , R 104 and R 106 , which may be the same or different, represent
a hydrogen atom,
a halogen atom,
C 1-6 alkyl,
C 1-10 alkoxy optionally substituted by a halogen atom or phenyl,
C 2-6 alkenylcarbonyloxy,
C 1-4 alkylcarbonyl, or
phenyl optionally substituted by a halogen atom,
R 105 represents
hydroxyl,
a halogen atom,
C 1-6 alkyl,
C 1-10 alkoxy optionally substituted by a halogen atom or phenyl,
C 2-6 alkenylcarbonyloxy,
C 1-4 alkylcarbonyl,
C 1-4 alkylthio, or
phenyl optionally substituted by a halogen atom,
R 103 and R 104 , R 104 and R 105 , and R 105 and R 106 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group,
R 107 represents
a hydrogen atom,
C 1-4 alkyl, or
phenyl optionally substituted by hydroxyl, C 1-4 alkyl, or C 1-4 alkoxy.
30 . The compound according to claim 29 , wherein
Z represents —O—, at least one of R 101 and R 102 represents methyl, and R 107 represents a hydrogen atom, methyl, ethyl, or phenyl optionally substituted by hydroxyl, C 1-4 alkyl or C 1-4 alkoxy.
31 . The compound according to claim 1 or pharmaceutically acceptable salt or solvate thereof, wherein formula (I) is represented by formula (200):
wherein
X represents CH or N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R 201 and R 202 , which may be the same or different, represent any group selected from the group consisting of
a hydrogen atom,
C 1-6 alkyl,
benzyl, and
groups of formulae (i), (ii-a), (iii-a), (iv-a), (v), and (vi),
(i) a group of formula (i):
wherein
R 51 and R 52 , which may be the same or different, represent
a hydrogen atom, or
C 1-8 alkyl optionally substituted by hydroxyl, an oxygen atom, amino, or a nitrogen atom,
R 51 and R 52 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, hydroxyl, an oxygen atom, aminocarbonyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 51 to combine with R 52 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
p is an integer of 2 to 4, and
the alkyl chain part in this group is optionally substituted by hydroxyl, or —OR e group wherein R e represents C 1-4 alkyl or C 1-4 alkylcarbonyl,
(ii) a group of formula (ii-a):
(iii) a group of formula (iii-a):
wherein r1 represents an integer of 2 to 4,
(iv) a group of formula (iv-a):
wherein
R 53 and R 54 , which may be the same or different, represent
a hydrogen atom, or
C 1-6 alkyl optionally substituted by hydroxyl, and
R 53 and R 54 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 53 to combine with R 54 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
(v) a group of formula (v):
wherein
R 55 represents C 1-4 alkyl and
t is an integer of 0 (zero) to 3, and
(vi) a group of formula (vi):
wherein
R 56 , R 57 and R 58 , which may be the same or different, represent
a hydrogen atom,
C 1-4 alkoxycarbonyl, or
C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom, and
u is an integer of 0 (zero) to 4,
R 203 to R 206 , which may be the same or different, represent
a hydrogen atom,
hydroxyl,
a halogen atom,
C 1-6 alkyl,
C 1-10 alkoxy optionally substituted by a halogen atom or phenyl,
C 2-6 alkenylcarbonyloxy,
C 1-4 alkylcarbonyl,
C 1-4 alkylthio, or
phenyl optionally substituted by a halogen atom,
R 203 and R 204 , R 204 and R 205 , and R 205 and R 206 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group,
provided that at least one of R 203 to R 206 is selected from a group other than a hydrogen atom, and
R 208 represents unsubstituted C 1-8 alkyl; C 1-4 alkyl substituted by phenyl; C 2-8 alkenyl; or phenyl optionally substituted by a halogen atom.
32 . The compound according to claim 31 , wherein
Z represents —O—, S—, or —C(═O)—, and R 208 represents unsubstituted C 1-8 alkyl; methyl substituted by phenyl; C 2-8 alkenyl; or phenyl.
33 . The compound according to claim 1 or pharmaceutically acceptable salt or solvate thereof, wherein formula (I) is represented by formula (300):
wherein
X represents CH or N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R 301 and R 302 , which may be the same or different, represent any group selected from the group consisting of
a hydrogen atom,
C 1-6 alkyl,
benzyl, and
groups of formulae (i), (ii-a), (iii-a), (iv-a), (v), and (vi),
(i) a group of formula (i):
wherein
R 51 and R 52 , which may be the same or different, represent
a hydrogen atom, or
C 1-8 alkyl optionally substituted by hydroxyl, an oxygen atom, amino, or a nitrogen atom,
R 51 and R 52 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, hydroxyl, an oxygen atom, aminocarbonyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 51 to combine with R 52 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
p is an integer of 2 to 4, and
the alkyl chain part in this group is optionally substituted by hydroxyl, or —OR e group wherein R e represents C 1-4 alkyl or C 1-4 alkylcarbonyl,
(ii) a group of formula (ii-a):
(iii) a group of formula (iii-a):
wherein r1 represents an integer of 2 to 4,
(iv) a group of formula (iv-a):
wherein
R 53 and R 54 , which may be the same or different, represent
a hydrogen atom, or
C 1-6 alkyl optionally substituted by hydroxyl, and
R 53 and R 54 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 53 to combine with R 54 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
(v) a group of formula (v):
wherein
R 55 represents C 1-4 alkyl and
t is an integer of 0 (zero) to 3, and
(vi) a group of formula (vi):
wherein
R 56 , R 57 and R 58 , which may be the same or different, represent
a hydrogen atom,
C 1-4 alkoxycarbonyl, or
C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom, and
u is an integer of 0 (zero) to 4,
R 303 to R 306 , which may be the same or different, represent
a hydrogen atom,
hydroxyl,
a halogen atom,
C 1-6 alkyl,
C 1-10 alkoxy optionally substituted by a halogen atom or phenyl,
C 2-6 alkenylcarbonyloxy,
C 1-4 alkylcarbonyl,
C 1-4 alkylthio, or
phenyl optionally substituted by a halogen atom,
R 303 and R 304 , R 304 and R 305 , and R 305 and R 306 each may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group,
provided that at least one of R 303 to R 306 is selected from a group other than a hydrogen atom, and
at least one of R 309 and R 310 represents a hydrogen atom and the other substituent represents
a hydrogen atom,
C 1-6 alkyl,
a saturated or unsaturated five- or six-membered carbocyclic group in which the carbocyclic group is optionally substituted by a halogen atom, or
naphthyl optionally substituted by a halogen atom, or
R 309 and R 310 combine with a nitrogen atom attached thereto to form a saturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms.
34 . The compound according to claim 33 , wherein
Z represents —O—, at least one of R 309 and R 310 represents a hydrogen atom and the other substituent represents a hydrogen atom, C 1-4 alkyl, a saturated or unsaturated six-membered carbocyclic group in which the carbocyclic group is optionally substituted by a halogen atom, or naphthyl, or R 309 and R 310 combine with a nitrogen atom attached thereto to form a saturated six-membered heterocyclic group which may further comprise one or more heteroatoms.
35 . The compound according to claim 1 or pharmaceutically acceptable salt or solvate thereof, wherein formula (I) is represented by formula (400):
wherein
X represents CH or N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R 401 and R 402 , which may be the same or different, represent any group selected from C 1-6 alkyl,
R 403 , R 404 , and R 406 represent a hydrogen atom, hydroxyl, or a halogen atom,
R 405 represents C 1-4 alkyl,
R 411 and R 412 combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group in which the heterocyclic group may further comprise one or more heteroatoms and is optionally substituted by C 1-4 alkyl optionally substituted by hydroxyl; or a saturated five- or six-membered heterocyclic group.
36 . The compound according to claim 35 , wherein
Z represents —O—, R 401 and R 402 represent methyl, R 411 and R 412 combine with a nitrogen atom attached thereto to form a saturated five- or six-membered heterocyclic group in which the heterocyclic group may further comprise one or more heteroatoms.
37 . The compound according to claim 1 or pharmaceutically acceptable salt or solvate thereof, wherein formula (I) is represented by formula (500):
wherein
X represents CH or N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R 501 and R 502 , which may be the same or different, represent any group selected from C 1-6 alkyl,
R 503 and R 506 represent a hydrogen atom,
R 504 and R 505 represent C 1-6 alkyl, and
R 513 represents C 1-4 alkyl, and
R 514 represents hydroxyl; C 1-4 alkoxy optionally substituted by phenyl; C 2-6 alkenyloxy; phenyloxy; or amino optionally substituted by a six-membered unsaturated heterocyclic group.
38 . The compound according to claim 37 , wherein
Z represents —O—, R 501 and R 502 represent methyl, R 503 and R 506 represent a hydrogen atom, R 504 and R 505 represent methyl, and
R 513 represents methyl.
39 . The compound according to claim 1 or pharmaceutically acceptable salt or solvate thereof, wherein formula (I) is represented by formula (600):
wherein
X represents or N,
Z represents —O—, —NH—, or —S—, or —C(═O)—,
R 601 and R 602 , which may be the same or different, represent any group selected from the group consisting of
a hydrogen atom,
C 1-6 alkyl,
benzyl, and
groups of formulae (i), (ii-a), (iii-a), (iv-a), (v), and (vi),
(i) a group of formula (i):
wherein
R 51 and R 52 , which may be the same or different, represent
a hydrogen atom, or
C 1-8 alkyl optionally substituted by hydroxyl, an oxygen atom, amino, or a nitrogen atom,
R 51 and R 52 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, hydroxyl, an oxygen atom, aminocarbonyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 51 to combine with R 52 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
p is an integer of 2 to 4, and
the alkyl chain part in this group is optionally substituted by hydroxyl, or —OR e group wherein R e represents C 1-4 alkyl or C 1-4 alkylcarbonyl,
(ii) a group of formula (ii-a):
(iii) a group of formula (iii-a):
wherein r1 represents an integer of 2 to 4,
(iv) a group of formula (iv-a):
wherein
R 53 and R 54 , which may be the same or different, represent
a hydrogen atom, or
C 1-6 alkyl optionally substituted by hydroxyl, and
R 53 and R 54 may combine with a nitrogen atom attached thereto to form a saturated or unsaturated five- or six-membered heterocyclic group which may further comprise one or more heteroatoms and in which the heterocyclic group is optionally substituted by C 1-4 alkyl, optionally substituted by hydroxyl, or a saturated or unsaturated five- or six-membered heterocyclic group, and the heterocyclic group optionally formed by allowing R 53 to combine with R 54 may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a bicyclic group,
(v) a group of formula (v):
wherein
R 55 represents C 1-4 alkyl and
t is an integer of 0 (zero) to 3, and
(vi) a group of formula (vi):
wherein
R 56 , R 57 and R 58 , which may be the same or different, represent
a hydrogen atom,
C 1-4 alkoxycarbonyl, or
C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom, and
u is an integer of 0 (zero) to 4,
R 625 represents a hydrogen atom,
R 626 represents a hydrogen atom, a halogen atom, or C 1-4 alkyl,
R 627 represents a hydrogen atom, a halogen atom, C 1-4 alkyl, C 1-4 alkoxy, or C 1-4 alkylthio,
R 626 and R 627 may combine with a carbon atom attached thereto to form an unsaturated six-membered carbocyclic or heterocyclic group,
R 628 represents
a hydrogen atom,
a halogen atom,
nitro,
cyano,
C 1-6 alkyl in which the alkyl group is optionally substituted by hydroxyl; phenyl; amino optionally substituted by C 1-4 alkyl; C 1-4 alkylcarbonyloxy; or a saturated or unsaturated six-membered heterocyclic group optionally substituted by C 1-4 alkyl,
C 1-8 alkoxy,
C 1-4 alkylcarbonyl,
C 2-6 alkenyl optionally substituted by a saturated or unsaturated six-membered carbocyclic group,
C 2-6 alkynyl optionally substituted by C 1-2 alkylsilyl,
a saturated or unsaturated three- to eight-membered carbocyclic oxy group,
a saturated or unsaturated six-membered carbocyclic carbonyl or heterocyclic carbonyl group optionally substituted by C 1-4 alkyl, or
a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by hydroxyl; cyano; a halogen atom; C 1-4 alkoxy; phenyloxy; C 1-4 alkylcarbonyl; amino optionally substituted by C 1-4 alkyl or C 1-4 alkylcarbonyl; aminocarbonyl optionally substituted by C 1-4 alkyl; or C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom.
40 . The compound according to claim 39 , wherein R 628 represents a saturated or unsaturated four- to seven-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by hydroxyl; cyano; a halogen atom; C 1-4 alkoxy; phenyloxy; C 1-4 alkylcarbonyl; amino optionally substituted by C 1-4 alkyl or C 1-4 alkylcarbonyl; aminocarbonyl optionally substituted by C 1-4 alkyl; or C 1-4 alkyl optionally substituted by hydroxyl or a halogen atom.
41 . The compound according to claim 1 or pharmaceutically acceptable salt or solvate thereof, wherein formula (I) is represented by formula (700):
wherein
X represents N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R 701 and R 702 , which may be the same or different, represent any group selected from C 1-6 alkyl,
R 729 represents a hydrogen atom,
R 730 represents a hydrogen atom or C 1-4 alkyl, and
R 731 and R 732 combine with a carbon atom attached thereto to form an unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a halogen atom or C 1-4 alkyl.
42 . The compound according to claim 41 , wherein
Z represents —O— and R 701 and R 702 represent methyl.
43 . The compound according to claim 1 , represented by formula (800), or a pharmaceutically acceptable salt or solvate thereof:
wherein
X represents N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R 801 and R 802 , which may be the same or different, represent any group selected from C 1-6 alkyl,
R 833 and R 834 represent a hydrogen atom, and
R 835 and R 836 combine with a carbon atom attached thereto to form an unsaturated five- or six-membered carbocyclic or heterocyclic group.
44 . The compound according to claim 43 , wherein
Z represents —O— or —S—, R 801 and R 802 represent methyl, R 835 and R 836 combine with a carbon atom attached thereto to form phenyl.
45 . The compound according to claim 1 or pharmaceutically acceptable salt or solvate thereof, wherein formula (I) is represented by formula (900):
wherein
X represents N,
Z represents —O—, —NH—, —S—, or —C(═O)—,
R 901 and R 902 , which may be the same or different, represent any group selected from C 1-6 alkyl
R 920 , R 921 , R 923 , and R 924 , which may be the same or different, represent
a hydrogen atom,
a halogen atom,
C 1-10 alkyl optionally substituted by hydroxyl, a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group,
C 1-8 alkoxy,
C 2-6 alkenyl optionally substituted by C 1-4 alkyl, C 1-4 alkoxy, an oxygen atom or phenyl,
phenylcarbonyl optionally substituted by C 1-4 alkyl,
amino optionally substituted by phenyl,
nitro, or
a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by C 1-6 alkyl,
provided that at least one of R 920 and R 924 is selected from a group other than a hydrogen atom,
R 922 represents
C 1-10 alkyl optionally substituted by hydroxyl, a saturated or unsaturated six-membered carbocyclic or heterocyclic group,
C 1-8 alkoxy,
amino optionally substituted by phenyl,
nitro, or
a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by C 1-6 alkyl, and
R 921 and R 922 , or R 922 and R 923 may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a halogen atom, C 1-4 alkyl, C 1-4 alkylcarbonyl, C 1-6 alkoxycarbonyl, or an oxygen atom, and the carbocyclic or heterocyclic group may condense with another saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group to form a tricyclic group together with the six-membered carbocyclic ring of formula (c).
46 . The compound according to claim 45 , wherein
at least one of R 920 and R 924 is selected from a group other than a hydrogen atom, and R 921 and R 922 , or R 922 and R 923 may combine with a carbon atom attached thereto to form a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group in which the carbocyclic or heterocyclic group is optionally substituted by a halogen atom, C 1-4 alkyl, C 1-4 alkylcarbonyl, C 1-6 alkoxycarbonyl, or an oxygen atom.
47 . A pharmaceutical composition comprising as an active ingredient the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof; and a pharmaceutically acceptable carrier.
48 - 53 . (canceled)
54 . A method for treating a disease for which TGFβ inhibition is effective therapeutically or prophylactically, comprising the step of administering a therapeutically or prophylactically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof to a patient who should undergo therapy of a disease for which inhibition activity is effective therapeutically or prophylactically.
55 . The method according to claim 54 , wherein the disease for which TGFβ inhibition is effective therapeutically or prophylactically is a disease involving fibrosis of an organ or a tissue.
56 . The method according to claim 54 , wherein the disease for which TGFβ inhibition is effective therapeutically or prophylactically is chronic renal disease, acute renal disease, hepatic fibrosis, cirrhosis, pulmonary fibrosis, scleroderma, wound healing, arthritis, congestive cardiac disease, ulcer, ocular disorder, cornea disorder, diabetic nephropathy, peritoneal sclerosis, arterial sclerosis, peritoneal adhesion, or subdermal adhesion.
57 . The method according to claim 54 , wherein the disease for which TGFβ inhibition is effective therapeutically or prophylactically is a malignant tumor.
58 . A method for amplifying cells in vitro, comprising the step of addition, into target cells in vitro, of the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof in an amount effective for promoting cell amplification to amplify cells.
59 . The method according to claim 58 , wherein said target cells are hematopoietic stem cells.
60 . A method for inhibiting the action of TGFβ on cells, comprising the step of applying an effective amount of the compound according to claim 1 to cells present in vitro or in vivo.
61 - 63 . (canceled)Join the waitlist — get patent alerts
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