Hydroxamic acid derivative
Provided is a novel compound which is useful as a pharmaceutical composition by inhibiting an LpxC activity, thereby exhibiting potent antimicrobial activity against gram-negative bacteria including Pseudomonas aeruginosa and its drug resistant bacteria. Provided is a hydroxamic acid derivative represented by the following general formula [1] or a pharmaceutically acceptable salt thereof:
1. A compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof:
wherein
R 1 and R 2 are the same or different and each represent a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group or a C 1-6 alkoxy group (the C 1-6 alkyl group, the C 1-6 alkoxy group and the C 3-8 cycloalkyl group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 11 )COR 12 , —N(R 11 )SO 2 R 12 , a cyano group, a carboxy group, a carbamoyl group, —CON(R 13 )(R 14 ), —SO 2 N(R 13 )(R 14 ), a C 1-6 alkylthio group, a C 1-6 alkylsulfonyl group, an aryloxy group, an aryl group, and a heterocyclic group”),
R 11 , R 12 , R 13 and R 14 are the same or different and each represent a hydrogen atom or a C 1-6 alkyl group,
R 13 and R 14 , together with the nitrogen atom to which they are attached, may form a saturated or unsaturated 5- or 6-membered ring which may further contain one or more nitrogen atoms, oxygen atoms or sulfur atoms,
R 3 represents a hydrogen atom or a C 1-6 alkyl group (the C 1-6 alkyl group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, and a di(C 1-6 alkyl)amino group”),
R 4 represents
a hydrogen atom,
a hydroxy group,
a C 1-6 alkoxy group,
a C 3-8 cycloalkoxy group,
an amino group,
a C 1-6 alkylamino group,
a di(C 1-6 alkyl)amino group,
a C 1-6 alkyl group, a C 3-8 cycloalkyl group
(the C 1-6 alkyl group and the C 3-8 cycloalkyl group may be substituted with 1 to 3 substituents which are the same or different and are selected from
“a halogen atom, a hydroxy group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 41 )COR 42 , —N(R 41 )SO 2 R 42 , a cyano group, a carboxy group, —CON(R 43 )(R 44 ), —SO 2 N(R 43 )(R 44 ), a C 1-6 alkylthio group, a C 1-6 alkylsulfonyl group, an aryl group, an aryloxy group, and a heterocyclic group (the aryl group, the aryloxy group, and the heterocyclic group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a benzyl group, a C 1-6 haloalkyl group, a C 1-6 hydroxyalkyl group, a C 2-8 alkoxyalkyl group, a hydroxy group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 45 )COR 46 , —N(R 45 )SO 2 R 46 , a cyano group, a carboxy group, —CON(R 47 )(R 48 ), —SO 2 N(R 47 )(R 48 ), a C 1-6 alkylthio group, and a C 1-6 alkylsulfonyl group”) ”),
an aryl group, or a heterocyclic group
(the aryl group and the heterocyclic group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 haloalkyl group, a C 1-6 hydroxyalkyl group, a C 2-8 alkoxyalkyl group, a hydroxy group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 45 )COR 46 , —N(R 45 )SO 2 R 46 , a cyano group, a carboxy group, —CON(R 47 )(R 48 ), —SO 2 N(R 47 )(R 48 ), a C 1-6 alkylthio group, and a C 1-6 alkylsulfonyl group”),
R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 and R 48 are the same or different and each represent a hydrogen atom or a C 1-6 alkyl group,
R 43 and R 44 , together with the nitrogen atom to which they are attached, may form a saturated or unsaturated 5- or 6-membered ring which may further contain one or more nitrogen atoms, oxygen atoms or sulfur atoms,
R 47 and R 48 , together with the nitrogen atom to which they are attached, may form a saturated or unsaturated 5- or 6-membered ring which may further contain one or more nitrogen atoms, oxygen atoms or sulfur atoms,
R 3 and R 4 , together with the nitrogen atom to which they are attached, may form a saturated or unsaturated 5- or 6-membered ring which may further contain one or more nitrogen atoms, oxygen atoms or sulfur atoms,
A 1 represents a divalent aryl group which may be substituted with 1 to 4 substituents which are the same or different and are selected from the following group of substituents, R a ):
the group of substituents, R a , consists of a halogen atom, a hydroxy group, an amino group (the amino group may be substituted with a C 2-6 alkanoyl group or one or two C 1-6 alkyl groups), a carboxy group, a carbamoyl group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 2-6 alkenyl group, and a C 1-6 alkoxy group (the C 1-6 alkyl group, the C 3-8 cycloalkyl group, the C 2-6 alkenyl group, and the C 1-6 alkoxy group may be substituted with 1 to 4 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, an amino group, a carboxy group, a C 1-6 alkylaminocarbonyl group, and a C 1-6 alkoxycarbonyl group”),
L represents —C≡C—, —C≡C—C≡C—, —CH═CH—, —CH═CH—C≡C—, or —C≡C—CH═CH—,
R 5 represents a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, or an aryl group,
m denotes 1, 2 or 3,
A 2 represents a divalent aryl group which may be substituted with 1 to 4 substituents which are the same or different and are selected from the following group of substituents, R b ):
the group of substituents, R b , consists of a halogen atom, an optionally protected hydroxy group, a mercapto group, a cyano group, a nitro group, an optionally protected amino group, an optionally protected formyl group, an optionally protected carboxy group, a carbamoyl group, a sulfo group, a ureido group, a guanidido group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 haloalkyl group, a C 1-6 hydroxyalkyl group, a C 1-6 alkoxy group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, a C 1-6 alkoxycarbonyl group, a C 2-6 alkanoyl group, and an aryl group,
W represents R 6 —X 1 —, R 6 —X 2 —Y 1 —X 1 —, R 6 —X 4 —Y 1 —X 2 —Y 3 —X 3 —, Q-X 1 —Y 2 —X 3 —, or Q-X 1 —Y 1 —X 2 —Y 3 —X 3 —,
Y 2 represents —O—, —NR 7 —, —CO—, —NR 7 CO—, —CONR 7 —, —S(O) n —, —OCO—, —COO—, —NR 7 SO 2 —, —SO 2 —NR 7 —, —OCOO—, —OCONR 7 —, —NR 7 CONR 8 —, or a bond,
Y 1 and Y 3 are the same or different and each represent —O—, —NR 7 —, —CO—, —NR 7 CO—, —CONR 7 —, —S(O) n —, —OCO—, —COO—, —NR 7 SO 2 —, —SO 2 NR 7 —, —OCOO—, —OCONR 7 —, or —NR 7 CONR 8 —,
n denotes 0, 1 or 2,
X 1 and X 3 are the same or different and each represent a C 1-10 alkylene group, a C 2-10 alkenylene group, a C 2-10 alkynylene group, a C 3-8 cycloalkylene group, —C 1-6 alkylene-C 3-8 cycloalkylene-C 1-6 alkylene- (the C 1-10 alkylene group, the C 2-10 alkenylene group, the C 2-10 alkynylene group, the C 3-8 cycloalkylene group, and the —C 1-6 alkylene-C 3-8 cycloalkylene-C 1-6 alkylene- may be substituted with 1 to 4 substituents which are the same or different and are selected from a group of substituents, R c , to be shown below), or a bond,
X 2 and X 4 are the same or different and each represent a C 1-10 alkylene group, a C 2-10 alkenylene group, a C 2-10 alkynylene group, or —C 1-6 alkylene-C 3-8 cycloalkylene-C 1-6 alkylene-(the C 1-10 alkylene group, the C 2-10 alkenylene group, the C 2-10 alkynylene group, and the -C 1-6 alkylene-C 3-8 cycloalkylene-C 1-6 alkylene- may be substituted with 1 to 4 substituents which are the same or different and are selected from the group of substituents, R c , to be shown below),
Q represents a C 3-8 cycloalkyl group, an aryl group, or a heterocyclic group (the C 3-8 cycloalkyl group, the aryl group and the heterocyclic group may be substituted with 1 to 4 substituents which are the same or different and are selected from the group of substituents, R c , to be shown below, and the heterocyclic group may have the different carbon atoms on the ring bridged with a C 1-6 alkylene group or —C 1-6 alkylene-O—C 1-6 alkylene-),
R 6 represents a hydrogen atom, a halogen atom, an optionally protected hydroxy group, a mercapto group, a cyano group, a nitro group, an optionally protected amino group, an optionally protected formyl group, an optionally protected carboxy group, a carbamoyl group, a sulfo group, an optionally protected phosphate group, a ureido group, a guanidido group, R 7 —O—NR 8 —CO—, R 8 —ON═CR 9 —, R 8 —ON═CR 9 —NH—, R 7 —O—NR 8 —CH═N—, (R 7 )(R 8 )N—N═CH—, R 8 —O—NR 8 —, N≡C—NR 8 — or a C 1-6 alkoxy group (the C 1-6 alkoxy group may be substituted with 1 to 3 hydroxy groups),
R 7 and R 8 are the same or different and each represent a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, an aryl group, or a heterocyclic group (the C 1-6 alkyl group, the C 3-8 cycloalkyl group, the aryl group and the heterocyclic group may be substituted with 1 to 4 substituents which are the same or different and are selected from the group of substituents, R c , to be shown below),
R 9 represents a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, an amino group, or a C 1-6 alkylamino group, and
the group of substituents, R c , consists of a halogen atom, a hydroxy group, a cyano group, a nitro group, an amino group (the amino group may be substituted with a C 2-6 alkanoyl group or one or two C 1-6 alkyl groups), a carboxy group, a carbamoyl group, a ureido group, a guanidido group, a C 1-6 alkyl group (the C 1-6 alkyl group may be substituted with a heterocyclic group), a C 1-6 hydroxyalkyl group, a C 1-6 haloalkyl group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group (the C 1-6 alkoxy group may be substituted with 1 to 3 substituents which are the same or different and are selected from a hydroxy group, a halogen atom, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, an aryl group and a heterocyclic group), a C 3-8 cycloalkoxy group, a C 1-6 alkoxycarbonyl group, a C 1-6 alkoxycarbonylamino group, a C 2-6 alkanoyl group, a C 1-6 alkylsulfonyl group, a C 1-6 alkylthio group, an aryl group, a heterocyclic group (the aryl group and the heterocyclic group may be substituted with 1 to 4 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, a cyano group, a nitro group, an amino group, a carboxy group and a C 1-6 alkyl group”), a C 1-6 alkylidene group (the C 1-6 alkylidene group may be substituted with a C 1-6 alkoxy group), a C 3-8 cycloalkylidene group, a monocyclic saturated heterocyclidene group (the monocyclic saturated heterocyclidene group may be substituted with 1 to 2 C 1-6 alkyl groups), and a hydroxyaminocarbonyl group.
2. The compound represented by the following formula [1] or the pharmaceutically acceptable salt thereof, according to claim 1 :
wherein
R 1 and R 2 are the same or different and each represent a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group or a C 1-6 alkoxy group (the C 1-6 alkyl group, the C 1-6 alkoxy group and the C 3-8 cycloalkyl group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 11 )COR 12 , —N(R 11 )SO 2 R 12 , a cyano group, a carboxy group, a carbamoyl group, —CON(R 13 )(R 14 ), —SO 2 N(R 13 )(R 14 ), a C 1-6 alkylthio group, a C 1-6 alkylsulfonyl group, an aryloxy group, an aryl group, and a heterocyclic group”),
R 11 , R 12 , R 13 and R 14 are the same or different and each represent a hydrogen atom or a C 1-6 alkyl group,
R 13 and R 14 , together with the nitrogen atom to which they are attached, may form a saturated or unsaturated 5- or 6-membered ring which may further contain one or more nitrogen atoms, oxygen atoms or sulfur atoms,
R 3 represents a hydrogen atom or a C 1-6 alkyl group (the C 1-6 alkyl group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, and a di(C 1-6 alkyl)amino group”),
R 4 represents
a hydrogen atom,
a hydroxy group,
a C 1-6 alkoxy group,
a C 3-8 cycloalkoxy group,
an amino group,
a C 1-6 alkylamino group,
a di(C 1-6 alkyl)amino group,
a C 1-6 alkyl group, a C 3-8 cycloalkyl group
(the C 1-6 alkyl group and the C 3-8 cycloalkyl group may be substituted with 1 to 3 substituents which are the same or different and are selected from
“a halogen atom, a hydroxy group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 41 )COR 42 , —N(R 41 )SO 2 R 42 , a cyano group, a carboxy group, —CON(R 43 )(R 44 ), —SO 2 N(R 43 )(R 44 ), a C 1-6 alkylthio group, a C 1-6 alkylsulfonyl group, an aryl group, an aryloxy group, and a heterocyclic group (the aryl group, the aryloxy group, and the heterocyclic group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a benzyl group, a C 1 -6 haloalkyl group, a C 1-6 hydroxyalkyl group, a C 2-8 alkoxyalkyl group, a hydroxy group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 45 )COR 46 , —N(R 45 )SO 2 R 46 , a cyano group, a carboxy group, —CON(R 47 )(R 48 ), —SO 2 N(R 47 )(R 48 ), a C 1-6 alkylthio group, and a C 1-6 alkylsulfonyl group”) ”),
an aryl group, or a heterocyclic group
(the aryl group and the heterocyclic group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 haloalkyl group, a C 1-6 hydroxyalkyl group, a C 2-8 alkoxyalkyl group, a hydroxy group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 45 )COR 46 , —N(R 45 )SO 2 R 46 , a cyano group, a carboxy group, —CON(R 47 )(R 48 ), —SO 2 N(R 47 )(R 48 )SO 2 N(R 47 )(R 48 ), a C 1-6 alkylthio group, and a C 1-6 alkylsulfonyl group”),
R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 and R 48 are the same or different and each represent a hydrogen atom or a C 1-6 alkyl group,
R 43 and R 44 , together with the nitrogen atom to which they are attached, may form a saturated or unsaturated 5- or 6-membered ring which may further contain one or more nitrogen atoms, oxygen atoms or sulfur atoms,
R 47 and R 48 , together with the nitrogen atom to which they are attached, may form a saturated or unsaturated 5- or 6-membered ring which may further contain one or more nitrogen atoms, oxygen atoms or sulfur atoms,
R 3 and R 4 , together with the nitrogen atom to which they are attached, may form a saturated or unsaturated 5- or 6-membered ring which may further contain one or more nitrogen atoms, oxygen atoms or sulfur atoms,
A 1 represents a divalent aryl group which may be substituted with 1 to 4 substituents which are the same or different and are selected from the following group of substituents, R a ):
the group of substituents, R a , consists of a halogen atom, a hydroxy group, an amino group (the amino group may be substituted with a C 2-6 alkanoyl group or one or two C 1-6 alkyl groups), a carboxy group, a carbamoyl group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 2-6 alkenyl group, and a C 1-6 alkoxy group (the C 1-6 alkyl group, the C 3-8 cycloalkyl group, the C 2-6 alkenyl group, and the C 1-6 alkoxy group may be substituted with 1 to 4 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, an amino group, a carboxy group, a C 1-6 alkylaminocarbonyl group, and a C 1-6 alkoxycarbonyl group”),
L represents —C≡C— or —C≡C—C≡C—,
R 5 represents a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, or an aryl group,
m denotes 1, 2 or 3,
A 2 represents a divalent aryl group which may be substituted with 1 to 4 substituents which are the same or different and are selected from the following group of substituents, R b ):
the group of substituents, R b , consists of a halogen atom, an optionally protected hydroxy group, a mercapto group, a cyano group, a nitro group, an optionally protected amino group, an optionally protected formyl group, an optionally protected carboxy group, a carbamoyl group, a sulfo group, a ureido group, a guanidido group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 haloalkyl group, a C 1-6 hydroxyalkyl group, a C 1-6 alkoxy group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, a C 1-6 alkoxycarbonyl group, a C 2-6 alkanoyl group, and an aryl group,
W represents R 6 —X 1 —, R 6 —X 2 —Y 1 —X 1 —, R 6 —X 4 —Y 1 —X 2 —Y 3 —X 3 —, Q-X 1 —Y 2 —X 3 —, or Q-X 1 —Y 1 —X 2 —Y 3 —X 3 —,
Y 2 represents —O—, —NR 7 —, —CO—, —NR 7 CO—, —CONR 7 —, —S(O) n —, —OCO—, —COO—, —NR 7 SO 2 —, —SO 2 —NR 7 —, —OCOO—, —OCONR 7 —, —NR 7 —CONR 8 —, or a bond,
Y 1 and Y 3 are the same or different and each represent —O—, —NR 7 —, —CO—, —NR 7 CO—, —CONR 7 —, —S(O) n —, —OCO—, —COO—, —NR 7 SO 2 , —SO 2 NR 7 —, —OCOO—, —OCONR 7 —, or —NR 7 CONR 8 —,
n denotes 0, 1 or 2,
X 1 and X 3 are the same or different and each represent a C 1-10 alkylene group, a C 2-10 alkenylene group, a C 2-10 alkynylene group (the C 1-10 alkylene group, the C 2-10 alkenylene group and the C 2-10 alkynylene group may be substituted with 1 to 4 substituents which are the same or different and are selected from a group of substituents, R c , to be shown below), or a bond,
X 2 and X 4 are the same or different and each represent a C 1-10 alkylene group, a C 2-10 alkenylene group, a C 2-10 alkynylene group, or -C 1-6 alkylene-C 3-8 cycloalkylene-C 1-6 alkylene -(the C 1-10 alkylene group, the C 2-10 alkenylene group, the C 2-10 alkynylene group, and the -C 1-6 alkylene-C 3-8 cycloalkylene-C 1-6 alkylene—may be substituted with 1 to 4 substituents which are the same or different and are selected from the group of substituents, R c , to be shown below),
Q represents a C 3-8 cycloalkyl group, an aryl group, or a heterocyclic group (the C 3-8 cycloalkyl group, the aryl group and the heterocyclic group may be substituted with 1 to 4 substituents which are the same or different and are selected from the group of substituents, R c , to be shown below),
R 6 represents a hydrogen atom, a halogen atom, an optionally protected hydroxy group, a mercapto group, a cyano group, a nitro group, an optionally protected amino group, an optionally protected formyl group, an optionally protected carboxy group, a carbamoyl group, a sulfo group, an optionally protected phosphate group, a ureido group, a guanidido group, R 7 —O—NR 8 —CO—, R 8 —ON═CR 9 —, R 8 —ON═CR 9 —NH—, R 7 —O—NR 8 —CH═N—, (R 7 )(R 8 )N—N═CH—, R 8 —O—NR 8 —, or N≡C—NR 8 —,
R 7 and R 8 are the same or different and each represent a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, an aryl group, or a heterocyclic group (the C 1-6 alkyl group, the C 3-8 cycloalkyl group, the aryl group and the heterocyclic group may be substituted with 1 to 4 substituents which are the same or different and are selected from the group of substituents, R c , to be shown below),
R 9 represents a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, an amino group, or a C 1-6 alkylamino group, and
the group of substituents, R c , consists of a halogen atom, a hydroxy group, a cyano group, a nitro group, an amino group (the amino group may be substituted with a C 2-6 alkanoyl group or one or two C 1-6 alkyl groups), a carboxy group, a carbamoyl group, a ureido group, a guanidido group, a C 1-6 alkyl group (the C 1-6 alkyl group may be substituted with a heterocyclic group), a C 1-6 hydroxyalkyl group, a C 1-6 haloalkyl group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group (the C 1-6 alkoxy group may be substituted with 1 to 3 hydroxy groups), a C 3-8 cycloalkoxy group, a C 1-6 alkoxycarbonyl group, a C 1-6 alkoxycarbonylamino group, a C 2-6 alkanoyl group, a C 1-6 alkylsulfonyl group, a C 1-6 alkylthio group, an aryl group, and a heterocyclic group (the aryl group and the heterocyclic group may be substituted with 1 to 4 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, a cyano group, a nitro group, an amino group, a carboxy group and a C 1-6 alkyl group”).
3. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 1 is a hydrogen atom or a C 1-6 alkyl group (the C 1-6 alkyl group may be substituted with the same or different 1 to 3 halogen atoms).
4. The compound or the pharmaceutically acceptable salt thereof, according to claim 3 , wherein R 1 is a C 1-6 alkyl group (the C 1-6 alkyl group may be substituted with the same or different 1 to 3 halogen atoms).
5. The compound or the pharmaceutically acceptable salt thereof, according to claim 4 , wherein R 1 is a methyl group.
6. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 2 is a hydrogen atom.
7. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 2 is a methyl group.
8. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein
R 3 is a hydrogen atom, and
R 4 is a C 1-6 alkyl group (the C 1-6 alkyl group may be substituted with a phenyl group or a monocyclic aromatic heterocyclic group (the phenyl group and the monocyclic aromatic heterocyclic group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 haloalkyl group, a C 1-6 hydroxyalkyl group, a C 2-8 alkoxyalkyl group, a hydroxy group, a C 1-6 alkoxy group, a C 3-8 cycloalkoxy group, an amino group, a C 1-6 alkylamino group, a di(C 1-6 alkyl)amino group, —N(R 45 )COR 46 , —CON(R 47 )(R 48 )”)).
9. The compound or the pharmaceutically acceptable salt thereof, according to claim 8 , wherein R 3 is a hydrogen atom, and R 4 is a methyl group.
10. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein A 1 is a phenylene group (the phenylene group may be substituted with 1 to 4 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, an amino group and a C 1-6 alkyl group”).
11. The compound or the pharmaceutically acceptable salt thereof, according to claim 10 , wherein A 1 is a phenylene group.
12. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein L is —C≡C—.
13. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein
W is R 6 —X 1 —,
X 1 is a methylene group or a bond,
R 6 is a hydrogen atom, an optionally protected hydroxy group, or R 8 —ON═CR 9 —,
R 8 is a hydrogen atom or a C 1-6 alkyl group (the C 1-6 alkyl group may be substituted with 1 to 4 substituents which are the same or different and are selected from a group of substituents, R c , to be shown below),
R 9 is a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, an amino group, or a C 1-6 alkylamino group, and
the group of substituents, R c , consists of a halogen atom and a hydroxy group.
14. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein
W is R 6 —X 2 —Y 1 —X 1 —,
Y 1 is —O— or —NR 7 —,
X 1 is a methylene group, an ethylene group (the methylene group and the ethylene group may be substituted with 1 to 2 methyl groups), a C 3-8 cycloalkylene group, or a bond,
X 2 is a C 1-4 alkylene group (the C 1-4 alkylene group may be substituted with 1 to 4 substituents which are the same or different and are selected from a group of substituents, R c , to be shown below),
R 6 is a hydrogen atom, a halogen atom, an optionally protected hydroxy group, or a C 1-6 alkoxy group,
R 7 is a hydrogen atom, a C 1-6 alkyl group or a C 3-8 cycloalkyl group (the C 1-6 alkyl group and the C 3-8 cycloalkyl group may be substituted with 1 to 4 substituents which are the same or different and are selected from the following group of substituents, R c ), and
the group of substituents, R c , consists of a halogen atom, a hydroxy group, and a C 1-6 alkyl group.
15. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein
W is Q-X 1 —Y 2 —X 3 —,
Y 2 is —O—, —NR 7 —, or a bond,
X 1 is a C 1-4 alkylene group (the C 1-4 alkylene group may be substituted with 1 to 4 substituents which are the same or different and are selected from a group of substituents, R c , to be shown below), or a bond,
X 3 is a methylene group, an ethylene group (the methylene group and the ethylene group may be substituted with 1 to 2 methyl groups), a C 3-8 cycloalkylene group, or a bond,
Q is a C 3-8 cycloalkyl group, an aryl group, or a heterocyclic group (the C 3-8 cycloalkyl group, the aryl group, or the heterocyclic group may be substituted with 1 to 4 substituents which are the same or different and are selected from the group of substituents, R c , shown below
R 7 is a hydrogen atom, a C 1-6 alkyl group or a C 3-8 cycloalkyl group (the C 1-6 alkyl group and the C 3-8 cycloalkyl group may be substituted with 1 to 4 substituents which are the same or different and are selected from the following group of substituents, R c ), and
the group of substituents, R c , consists of a halogen atom, a hydroxy group, a C 1-6 alkyl group, a C 1-6 hydroxyalkyl group, a C 1-6 haloalkyl group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group (the C 1-6 alkoxy group may be substituted with 1 to 3 hydroxy groups or halogen atoms), a C 3-8 cycloalkoxy group, a C 2-6 alkanoyl group, a C 1-6 alkylidene group (the C 1-6 alkylidene group may be substituted with a C 1-6 alkoxy group), and a hydroxyaminocarbonyl group.
16. The compound or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein
W is a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group, or a C 1-6 alkylamino group (the C 1-6 alkyl group, the C 1-6 alkoxy group and the C 1-6 alkylamino group may be substituted with 1 to 3 substituents which are the same or different and are selected from “a halogen atom, a hydroxy group, a C 1-6 alkoxy group and a morpholino group”).
17. A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.