Acylthiourea compound or salt thereof, and use thereof

1. An acylthiourea compound represented by formula (I):

wherein each of R 1 and R 2 , which may be the same or different, represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-10 cycloalkyl group, an optionally substituted C 6-14 aromatic hydrocarbon group, or an optionally substituted saturated or unsaturated heterocyclic group, or R 1 and R 2 may form, together with a nitrogen atom to which they are attached, an optionally substituted nitrogen-containing heterocyclic ring;

R 3 represents a C 1-6 alkyl group; and

each of R 4 , R 5 , and R 6 , which may be identical to or different from one another, represents a hydrogen atom, a halogen atom, an optionally substituted C 1-6 alkyl group, a C 1-6 alkoxy group, a C 1-6 alkylamino group, an optionally substituted aromatic hydrocarbon group, or an optionally substituted saturated or unsaturated heterocyclic group, or R 5 and R 6 may form a ring together with the phenyl ring to which they are attached,

or a salt thereof.

2. The acylthiourea compound according to claim 1 or a salt thereof, wherein

R 1 is a hydrogen atom or a C 1-3 alkyl group;

R 2 is a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 6-14 aromatic hydrocarbon group, or an optionally substituted saturated or unsaturated heterocyclic group, or

R 1 and R 2 may form, together with the nitrogen atom to which they are attached, an optionally substituted saturated nitrogen-containing heterocyclic group;

R 3 is a C 1-3 alkyl group; R 4 is a halogen atom; and

each of R 5 and R 6 , which are the same or different, is a hydrogen atom, a halogen atom, a C 1-3 alkyl group which may have a halogen atom as a substituent or C 1-3 alkoxy group.

3. The acylthiourea compound according to claim 1 or a salt thereof, wherein

R 1 is a hydrogen atom or a methyl group;

R 2 is an optionally substituted C 1-6 alkyl group, an optionally substituted phenyl group, or an optionally substituted 5- to 7-membered heterocyclic group which has 1 or 2 nitrogen atom(s) or sulfur atom(s), or

R 1 and R 2 form, together with the nitrogen atom to which they are attached, an optionally substituted pyrrolidinyl group or an optionally substituted piperidinyl group;

R 3 is a methyl group;

R 4 is a fluorine atom or a chlorine atom;

R 5 is a hydrogen atom or a halogen atom; and

R 6 is a hydrogen atom, a halogen atom, a trifluoromethyl group or a methoxy group.

4. The acylthiourea compound according to claim 1 or a salt thereof, wherein

R 1 is a hydrogen atom;

R 2 is a C 1-6 alkyl group which may have a substituent, said substituent being a hydroxyl group, a C 3-10 cycloalkyl group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 1-6 alkylamino group, a C 1-6 alkanoylamino group, a C 1-6 alkylsulfonyl group, an optionally substituted C 6-14 aromatic hydrocarbon group, an optionally substituted saturated or unsaturated heterocyclic group, an optionally substituted saturated or unsaturated heterocyclic-carbonyl group, an optionally substituted C 1-6 alkylaminocarbonyl group, or an optionally substituted saturated or unsaturated heterocyclic-carbonyl group;

R 3 is a methyl group;

R 4 is a fluorine atom or a chlorine atom;

R 5 is a hydrogen atom; and

R 6 is a hydrogen atom, a fluorine atom, or a chlorine atom.

5. The acylthiourea compound according to claim 1 or a salt thereof, wherein R 2 is a C 1-4 alkyl group which may have a substituent, said substituent being a hydroxyl group, a cyclohexyl group, a C 1-3 alkoxy group, a C 1-6 alkylamino group, an acetylamino group, a methylsulfonyl group, a phenyl group, a 5- to 7-membered heterocyclic group having 1 to 4 nitrogen and/or oxygen atom(s), a C 1-6 alkylaminocarbonyl group, or a 5- to 7-membered heterocyclic-carbonyl group having 1 or 2 nitrogen and/or oxygen atom(s), wherein said C 1-3 alkoxy group may further have a hydroxyl group as a substituent; said C 1-6 alkylaminocarbonyl group may further have as a substituent a hydroxyl group or a C 1-6 alkoxy group; said heterocyclic group may further have as a substituent a C 1-6 alkyl group or an oxo group; and said heterocyclic-carbonyl group may further have a C 1-6 alkyl group as a substituent, said C 1-6 alkyl group optionally having a halogen atom or a hydroxyl group.

6. The acylthiourea compound according to claim 1 or a salt thereof, wherein R 2 is a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, or a sec-butyl group, wherein the substituent of any one of said alkyl groups is a hydroxyl group, a cyclohexyl group, a methoxy group, an ethoxy group, an isopropyloxy group, a diethylamino group, an acetylamino group, a methylsulfonyl group, a phenyl group, a pyrrolidinyl group, a morpholino group, a dioxolanyl group, a tetrahydropyranyl group, a pyridyl group, a triazolyl group, an ethylaminocarbonyl group, a dimethylaminocarbonyl group, a methylbutylaminocarbonyl group, a pyrrolidinylcarbonyl group, or a morpholinocarbonyl group; said alkoxy group may further have a hydroxyl group as a substituent; said heterocyclic group may further have as a substituent a methyl group or an oxo group; said alkylaminocarbonyl group may further have as a substituent a hydroxyl group or a methoxy group; and said heterocyclic-carbonyl group may further have as a substituent a fluorine atom or a methyl group optionally having a hydroxyl group.

7. The acylthiourea compound according to claim 1 or a salt thereof, which is selected from the group consisting of:

4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide;

4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-(methoxyethyl)quinoline-6-carboxamide;

4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-(2-morpholinoethyl)quinoline-6-carboxamide;

4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-(2-morpholino-2-oxoethyl)quinoline-6-carboxamide;

4-(2-fluoro-4-(3-(2-(4-fluorophenyl)acetyl)thioureido)phenoxy)-N-(2-hydroxybutyl)-7-methoxyquinoline-6-carboxamide;

4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-N-(2-hydroxy-2-methylpropyl)-7-methoxyquinoline-6-carboxamide;

(S)-4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-N-(1-hydroxybutan-2-yl)-7-methoxyquinoline-6-carboxamide;

4-(2-fluoro-4-(3-(2-(4-fluorophenyl)acetyl)thioureido)phenoxy)-7-methoxy-N-(2-morpholinoethyl)quinoline-6-carboxamide;

(S)-4-(2-fluoro-4-(3-(2-(4-fluorophenyl)acetyl)thioureido)phenoxy)-N-(1-hydroxybutan-2-yl)-7-methoxyquinoline-6-carboxamide;

(S)-4-(2-fluoro-4-(3-(2-(2-fluorophenyl)acetyl)thioureido)phenoxy)-N-(1-hydroxybutan-2-yl)-7-methoxyquinoline-6-carboxamide; and

(S)-4-(4-(3-(2-(4-chlorophenyl)acetyl)thioureido)-2-fluorophenoxy)-N-(1-hydroxybutan-2-yl)-7-methoxyquinoline-6-carboxamide.

8. A pharmaceutical agent, comprising, as an active ingredient, the acylthiourea compound according to any one of claims 1 to 7 or a salt thereof.

9. An antitumor agent, comprising, as an active ingredient, the acylthiourea compound according to any one of claims 1 to 7 or a salt thereof.

10. A pharmaceutical composition, comprising:

the acylthiourea compound according to any one of claims 1 to 7 or a salt thereof; and

a pharmaceutically acceptable carrier.

11. A method of producing an antitumor agent, the method comprising:

combining the acylthiourea compound according to any one of claims 1 to 7 or a salt thereof, with a pharmaceutically acceptable carrier.

12. A method for treatment of a tumor, the method comprising:

administering to a subject in need thereof, an effective amount of the acylthiourea compound according to any one of claims 1 to 7 or a salt thereof.