Quinoline derivative and quinazoline derivative inhibiting self-phosphorylation of hepatocytus prolifertor receptor and medicinal composition containing the same

1. A method for treating gastric cancer, comprising the step of administering a therapeutically effective amount of a compound represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof to a mammal

wherein

X represents CH;

Z represents O or S;0

L represents O or S;

M represents

—C(—R 10 )(—R 11 )— where R 10 and R 11 , which may be the same or different, represent a hydrogen atom, C 1-4 alkyl, or C 1-4 alkoxy, or

—N(—R 12 )— wherein R 12 represents a hydrogen atom or C 1-4 alkyl;

R 1 , R 2 , and R 3 , which may be the same or different, represent

a hydrogen atom,

hydroxyl,

a halogen atom,

nitro,

amino,

C 1-6 alkyl,

C 2-6 alkenyl,

C 2-6 alkynyl, or

C 1-6 alkoxy,

in which one or two hydrogen atoms on the amino group are optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy, and

in which the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy groups are optionally substituted by hydroxyl; a halogen atom; C 1-6 alkoxy; C 1-6 alkylcarbonyl; C 1-6 alkoxy carbonyl; amino on which one or two hydrogen atoms is optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy; or a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy;

R 4 represents a hydrogen atom;

R 5 , R 6 , R 7 , and R 8 , which may be the same or different, represent a hydrogen atom, a halogen atom, C 1-4 alkyl, or C 1-4 alkoxy;

R 9 represents

C 1-6 alkyl on which one or more hydrogen atoms are substituted by —R 14 , -T-R 15 , or —NR 16 R 17 wherein T represents —O—, —S—, or —NH—; R 14 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; R 15 , R 16 , and R 17 , which may be the same or different, represent C 1-6 alkyl or a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; the three- to eight-membered carbocyclic or heterocyclic group represented by R 14 , R 15 , R 16 , and R 17 is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring; when the three- to eight-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form an alkylene chain; and the three- to eight-membered carbocyclic or heterocyclic group may be a bicyclic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group, or

—N(—R 18 )(—R 19 ) wherein R 18 and R 19 , which may be the same or different, represent a hydrogen atom; C 1-6 alkyl which is optionally substituted by C 1-6 alkoxy, C 1-6 alkylthio, or a saturated or unsaturated three- or eight-membered carbocyclic or heterocyclic group in which the three- to eight-membered carbocyclic or heterocyclic group is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring and, when the three- to eight-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form an alkylene chain, or the three- to eight-membered carbocyclic or heterocyclic group may be a bicyclic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; or a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring and in which, when the three- to eight-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form an alkylene chain, or the three- to eight-membered carbocyclic or heterocyclic group may be a bicyclic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group.

2. The method according to claim 1 , wherein R 1 and R 4 a hydrogen atom and R 2 and R 3 represent a group other than a hydrogen atom.

3. The method according to claim 1 , wherein all of R 5 , R 6 , R 7 , and R 8 represent a hydrogen atom, or any one or two of R 5 , R 6 , R 7 , and R 8 represent a group other than a hydrogen atom with all the remaining groups representing a hydrogen atom.

4. The method according to claim 1 , wherein the substituted alkyl group represented by R 9 represents —(CH 2 )p-R 14 , —(CH 2 )p-T-R 15 , or —(CH 2 )p-NR 16 R 17 wherein p is an integer of 1 to 6 and R 14 , R 15 , R 16 , R 17 , and T are as defined in claim 1 .

5. The method according to claim 1 , wherein R 18 represents a hydrogen atom or C 1-6 alkyl; R 19 represents C 1-6 alkyl which is optionally substituted by an optionally substituted saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group; or an optionally substituted saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group.

6. The method according to claim 1 , wherein X represents CH, Z represents O, L represents O, M represents —N(—R 12 )—, R 1 and R 4 represent a hydrogen atom, R 2 represents unsubstituted C 1-6 alkoxy, R 3 represents optionally substituted C 1-6 alkoxy, and all of R 5 , R 6 , R 7 , and R 8 represent a hydrogen atom, or any one of R 5 , R 6 , R 7 , and R 8 represents a group other than a hydrogen atom with all the remaining groups representing a hydrogen atom.

7. The method according to claim 1 , wherein X represents CH, Z represents O, L represents O, M represents —C(—R 10 )(—R 11 )—, R 1 and R 4 represent a hydrogen atom, R 2 represents unsubstituted C 1-6 alkoxy group, R 3 represents optionally substituted C 1-6 alkoxy, and all of R 5 , R 6 , R 7 , and R 8 represent a hydrogen atom, or any one of R 5 , R 6 , R 7 , and R 8 represents a group other than a hydrogen atom with all the remaining groups representing a hydrogen atom.

8. The method according to claim 1 , wherein X represents CH, Z represents O, L represents S, M represents —N(—R 12 )—, R 1 and R 4 represent a hydrogen atom, R 2 represent unsubstituted C 1-6 alkoxy, R 3 represents optionally substituted C 1-6 alkoxy, and all of R 5 , R 6 , R 7 , and R 8 represent a hydrogen atom, or any one of R 5 , R 6 , R 7 , and R 8 represents a group other than a hydrogen atom with all the remaining groups representing a hydrogen atom.

9. The method according to claim 1 , wherein said compound is represented by formula (100):

wherein

R 103 represents hydroxyl or C 1-4 alkoxy which is optionally substituted by a halogen atom; hydroxyl; amino on which one or two hydrogen atoms are optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy; or a saturated or unsaturated five- to seven-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy,

R 105 , R 106 , R 107 , R 108 , which may be the same or different, represents a hydrogen atom, a halogen atom, C 1-4 alkyl, or C 1-4 alkoxy, and

R 109 represents

C 1-6 alkyl on which one or more hydrogen atoms are substituted by —R 114 , -T-R 115 , or —NR 116 R 117 in which T represents —O—, —S—, or —NH—; R 114 represents saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; R 115 represents C 1-6 alkyl or a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; R 116 and R 117 , which may be the same or different, represent C 1-6 alkyl or a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; the three- to eight-membered carbocyclic or heterocyclic group represented by R 114 , R 115 , R 116 , and R 117 is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring; when the three- to eight-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form an alkylene chain, or the three- to eight-membered carbocyclic or heterocyclic group may be a bicylic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group.

10. The method according to claim 9 , wherein the substituted alkyl group represented by R 109 represents —(CH 2 )p-R 114 , —(CH 2 )p-T-R 115 , or —(CH 2 )p-NR 116 R 117 in which p is an integer of 1 to 6, R 114 , R 115 , R 116 , R 117 , and T are as defined in claim 9 .

11. The method according to claim 1 , wherein said compound is represented by formula (200):

wherein

R 203 represents hydroxyl or C 1-4 alkoxy which is optionally substituted by a halogen atom; hydroxyl; amino on which one or two hydrogen atoms are optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy; or a saturated or unsaturated five- to seven-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy,

R 205 , R 206 , R 207 , and R 208 , which may be the same or different, represent a hydrogen atom, a halogen atom, C 1-4 alkyl, or C- 1-4 alkoxy, and

R 209 represents

C 1-6 alkyl on which one or more hydrogen atoms are substituted by —R 214 , -T-R 215 , or —NR 216 R 217 wherein T represents —O—, —S—, or —NH—; R 214 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; R 215 represents C 1-6 alkyl or a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; R 216 and R 217 , which may be the same or different, represent C 1-6 alkyl or a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group; the three- to eight-membered carbocyclic or heterocyclic group represented by R 214 , R 215 , R 216 , and R 217 is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring; when the three- to eight-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form an alkylene chain; and the three- to eight-membered carbocyclic or heterocyclic group may be a bicylic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group.

12. The method according to claim 11 , wherein the substituted alkyl group represented by R 209 represents —(CH 2 )p-R 214 , —(CH 2 )p-T-R 215 , or —(CH 2 )p-NR 216 R 217 in which p is an integer of 1 to 6.

13. The method according to claim 1 , wherein said compound is represented by formula (300):

wherein

R 303 represents hydroxyl or C 1-4 alkoxy which is optionally substituted by a halogen atom or a saturated or unsaturated six-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy,

R 305 , R 306 , R 307 , and R 308 , which may be the same or different, represent a hydrogen atom, a halogen atom, C 1-4 alkyl, or C 1-4 alkoxy,

R 310 and R 311 represent a hydrogen atom, C 1-4 alkyl, or C 1-4 alkoxy,

R 318 represents a hydrogen atom or C 1-4 alkyl,

R 319 represents

C 1-4 alkyl which is optionally substituted by a saturated or unsaturated six-membered carbocyclic group which is optionally substituted by C 1-6 alkyl; C 1-6 alkoxy; a halogen atom; nitro; trifluoromethyl; C 1-6 alkoxy carbonyl; cyano; cyano C 1-6 alkyl; C 1-6 alkylthio; phenoxy; acetyl; or a saturated or unsaturated five- or six-membered heterocyclic ring and in which, when substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form an alkylene chain, or may be a bicylic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group, or

a saturated or unsaturated four- to seven-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring; when the four- to seven-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form an alkylene chain; and the four- to seven-membered carbocyclic or heterocyclic group may be a bicyclic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group.

14. The method according to claim 1 , wherein said compound is represented by formula (400):

wherein

R 405 , R 406 , R 407 , and R 408 , which may be the same or different, represent a hydrogen atom, a halogen atom, C 1-4 alkyl, or C 1-4 alkoxy,

R 419 represents an unsaturated five- or six-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring; when the five- or six-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form an alkylene chain; and the five- or six-membered carbocyclic or heterocyclic group may be a bicylic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group.

15. The method according to claim 1 , wherein said compound is represented by formula (500):

wherein

X represents CH,

when L represents O and M represents —N(—R 12 )—, Q represents CH 2 or NH,

when L represents O and M represents —C(—R 10 )(—R 11 )—, Q represents NH,

when L represents S and M represents —N(—R 12 )—, Q represents CH 2 ,

R 503 represents hydroxyl or C 1-4 alkoxy which is optionally substituted by a halogen atom; hydroxyl; amino on which one or two hydrogen atoms are optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy; or a saturated or unsaturated five- to seven-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl which is optionally substituted by hydroxyl or C 1-6 alkoxy,

R 505 , R 506 , R 507 , and R 508 , which may be the same or different, represent a hydrogen atom, a halogen atom, C 1-4 alkyl, or C 1-4 alkoxy, and

R 520 represents a saturated or unsaturated five- or six-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, or a halogen atom.

16. The method according to claim 1 , wherein said compound is selected from:

(1) N-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]-N′-phenylacetylthiourea;

(2) N-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-N′-[2-(4-fluorophenyl)acetyl]thiourea;

(3) N-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-N′-[2-(4-fluorophenyl)acetyl]urea;

(4) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-phenyl-acetylurea;

(5) N-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-N′-(4-fluorophenyl)malonamide;

(6) N-[3-chloro-4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-N′-(2,4-difluorophenyl)malonamide;

(7) 1-(2-cyclopentylsulfanylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]urea;

(8) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-3-[2-(2,3-dihydro-1H-1-indol-1-yl)acetyl]-urea;

(9) N-phenyl-({[4-(6,7-dimethoxy-quinolin-4-yloxy)-anilino]carbonyl}amino)methanamide;

(10) N-(4-fluorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(11) 1-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)quinolin-4-yloxy]phenyl}-3-phenylacetylurea;

(12) 1-(3-fluoro-4-{6-methoxy-7-[4-(4-methyl-piperazin-1-yl)-butoxy]quinolin-4-yloxy}phenyl)-3-phenylacetylurea;

(13) 1-{3-fluoro-4-[6-methoxy-7-(2-piperidin-1-yl-ethoxy)quinolin-4-yloxy]phenyl}-3-phenylacetylurea;

(14) 1-{4-[7-(3-chloro-propoxy)-6-methoxyquinolin-4-yloxy]-3-fluorophenyl}-3-phenylacetylurea;

(15) N-(2,4-difluorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-2-methylmalonamide;

(16) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluorophenyl]-3-phenylacetylurea;

(17) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]-3-phenylacetylurea;

(18) 1-[3-chloro-4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-3-phenylacetylurea;

(19) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-(2-thiophen-3-ylacety)urea;

(20) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-(2-thiophen-3-ylacety)urea;

(21) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-3-(2-thiophen-3-ylacetyl)urea;

(22) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-[2-(4-fluorophenyl)acetyl]urea;

(23) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro-phenyl]-3-[2-(4-fluorophenyl)acetyl]urea;

(24) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(4-fluorophenyl)acetyl]urea;

(25) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-[2-(2-fluorophenyl)acetyl]urea;

(26) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(2-fluorophenyl)acetyl]urea;

(27) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(2-fluorophenyl)acetyl]urea;

(28) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-3-[2-(2-fluorophenyl)acetyl]urea;

(29) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-thiophen-2-ylacetyl)urea;

(30) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-(2-thiophen-2-ylacety)urea;

(31) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-(2-thiophen-2-ylacety)urea;

(32) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-3-(2-thiophen-2-ylacetyl)urea;

(33) 1-[2-(2,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluoropphenyl]urea;

(34) 1-[2-(2,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoropphenyl]urea;

(35) 1-[2-(3,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)acetyl]urea;

(36) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(3-fluorophenyl)acetyl]urea;

(37) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(3-fluorophenyl)acetyl]urea;

(38) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-methoxyphenyl]-3-[2-(4-fluorophenyl)]urea;

(39) 1-[2-(3,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]urea;

(40) 1-[4-(7-benzyloxy-6-methoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(4-fluorophenyl)acetyl]urea;

(41) 1-{3-fluoro-4-[6-methoxy-7-(4-morpholin-4-yl-butoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-acetyl]urea;

(42) 1-{3-fluoro-4-[6-methoxy-7-(4-piperidine-1-yl-butoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-acetyl]urea;

(43) 1-(3-fluoro-4-{6-methoxy-7-[4-(4-methyl-piperazin-1-yl)-butoxy]quinolin-4-yloxy}phenyl)-3-[2-(4-fluorophenyl)acetyl]urea;

(44) 1-{2-fluoro-4-[6-methoxy-7-(4-morpholin-4-yl-butoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-actyl]urea;

(45) 1-{2-fluoro-4-[6-methoxy-7-(4-piperidine-1-yl-butoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-acetyl]urea;

(46) 1-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-acetyl]urea;

(47) 1-{3-fluoro-4-[6-methoxy-7-(3-piperidin-1-yl-propoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-acetyl]urea;

(48) 1-{3-fluoro-4-[6-methoxy-7-(2-piperidin-1-yl-ethoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-acetyl]urea;

(49) 1-(3-fluoro-4-{6-methoxy-7-[2-(4-methyl-piperazin-1-yl)-ethoxy]quinolin-4-yloxy}phenyl)-3-[2-(4-fluorophenyl)acetyl]urea;

(50) 1-{2-fluoro-4-[6-methoxy-7-(3-piperidin-1-yl-propoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-acetyl]urea;

(51) 1-(2-fluoro-4-{6-methoxy-7-[3-(4-methyl-piperazin-1-yl)-propoxy]quinolin-4-yloxy}phenyl)-3-[2-(4-fluorophenyl)acetyl]urea;

(52) 1-{3-fluoro-4-[6-methoxy-7-(3-piperidin-1-yl-propoxy)quinolin-4-yloxy]phenyl}-3-phenylacetylurea;

(53) 1-(3-fluoro-4-{6-methoxy-7-[3-(4-methyl-piperazin-1-yl)-propoxy]-quinolin-4-yloxy}phenyl)-3-phenylacetylurea;

(54) 1-{3-fluoro-4-[6-methoxy-7-(2-morpholin-4-yl-ethoxy)quinolin-4-yloxy]phenyl}-3-phenylacetylurea;

(55) 1-{3-fluoro-4-[6-methoxy-7-(2-morpholin-4-yl-ethoxy)quinolin-4-yloxy]phenyl}-3-[2-(4-fluorophenyl)-acetyl]urea;

(58) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluorophenyl]-3-phenylacetylthiourea;

(59) 1-[2-(2-chlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]thiourea;

(60) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-phenylacetylthiourea;

(61) 1-(2-cyclohexylacetyl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]thiourea;

(62) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(3-ethoxypropionyl)thiourea;

(63) 1-[3-chloro-4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-3-phenylacetylthiourea;

(64) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-(3-o-tolylpropionyl)thiourea;

(65) 1-[2-chloro-4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-3-phenylacetylthiourea;

(66) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-thiophen-2-ylacetyl)thiourea;

(67) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-methyl-phenyl]-3-phenylacetylthiourea;

(68) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-methoxyphenyl]-3-phenylacetylthiourea;

(69) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-methoxyphenyl]-3-phenylacetylthiourea;

(70) 1-[3,5-dichloro-4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-phenylacetylthiourea;

(71) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(4-fluorophenyl)acetyl]thiourea;

(72) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluoro-phenyl]-3-[2-(4-fluorophenyl)acetyl]thiourea;

(73) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-3-[2-(4-fluorophenyl)acetyl]thiourea;

(74) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluoro-phenyl]-3-[2-(3-fluorophenyl)acetyl]thiourea;

(75) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(3-fluorophenyl)acetyl]thiourea;

(76) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-3-[2-(3-fluorophenyl)acetyl]thiourea;

(77) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-m-tolylacetyl)thiourea;

(78) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-3-(2-m-tolylacetyl)thiourea;

(79) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-o-tolylacetyl)thiourea;

(80) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluoro-phenyl]-3-[2-(2-fluorophenyl)acetyl]thiourea;

(81) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(2-fluorophenyl)acetyl]thiourea;

(82) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-3-(2-p-tolylacetyl)thiourea;

(83) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(2-methoxyphenyl)acetyl]thiourea;

(84) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]-3-(2-o-tolylacetyl)thiourea;

(85) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-(2-thiophen-3-ylacetyl)thiourea;

(86) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-methoxyphenyl]-3-(2-thiophen-3-ylacetyl)thiourea;

(87) 1-[2-(2-chlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(88) 1-(2-bicyclo[2.2.1]hepto-7-ylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]thiourea;

(89) 1-(2-bicyclo[2.2.1]hepto-7-ylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]thiourea;

(90) 1-(2-bicyclo[2.2.1]hepto-7-ylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(91) 1-(2-bicyclo[2.2.1]hepto-7-ylacetyl)-3-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]thiourea;

(92) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluorophenyl]-3-(2-p-tolylacetyl)thiourea;

(93) 1-[2-(2,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(94) 1-[2-(2,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(95) 1-[2-(2,6-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(96) 1-[2-(2,5-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(97) 1-[2-(2,6-dichlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(98) N-(2,4-difluorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluorophenyl]malonamide;

(99) N-(2,4-difluorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]malonamide;

(100) N-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-N′-phenylmalonamide;

(101) N-cycloheptyl-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(102) N-(2,4-difluorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(103) N-(2,4-difluorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-2-methoxymalonamide;

(104) N-(2,4-difluorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-2,2-dimethylmalonamide;

(105) N-(4-methyl-2-pyridyl)-({[4-(,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(106) 1-[3-fluoro-4-(7-hydroxy-6-methoxy-quinolin-4-yloxy)phenyl]-3-phenylacetylurea;

(110) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(2-diethylaminoacetyl)urea;

(111) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(2-pyrrolidin-1-ylacetyl)urea;

(112) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(isopropylmethylamino)acetyl]urea;

(113) 1-(2-cyclohexylsulfanylacetyl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]urea;

(114) 1-(2-cyclohexylsulfanylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]urea;

(115) 1-(2-cyclohexylsulfanylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]urea;

(116) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(2-cyclopentylsulfanylacetyl)urea;

(117) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-o-tolylaminoacetyl)urea;

(118) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-thiophen-3-ylacetyl)urea;

(119) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(6-methyl-3,4-dihydro-2H-quinolin-1-yl)acetyl]urea;

(120) 1-[2-(4-benzyl-piperidin-1-yl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]urea;

(121) 1-[2-(2,3-dihydro-1H-1-indol-1-yl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]urea;

(122) 1-[2-(2,3-dihydro-1H-1-indol-1-yl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]urea;

(123) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(2-[1,2,3]triazol-1-ylacetyl)urea;

(124) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluorophenyl]-3-(2-p-tolylacetyl)urea;

(125) 1-(2-bicyclo[2.2.1]hepto-7-ylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]urea;

(126) 1-(2-bicyclo[2.2.1]hepto-7-ylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]urea;

(127) 1-(2-bicyclo[2.2.1]hepto-7-ylacetyl)-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]urea;

(128) 1-(2-bicyclo[2.2.1]hepto-7-ylacetyl)-3-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]urea;

(129) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-phenylsulfanylacetyl)urea;

(130) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(1-methyl-1H-imidazlo-2-ylsulfanyl)-acetyl]urea;

(131) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(2-thiomorpholin-4-ylacetyl)urea;

(132) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(2-thiomorpholin-4-ylacetyl)urea;

(133) 1-[2-(2,5-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]urea;

(134) 1-[2-(2,6-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]urea;

(135) 1-[2-(2,6-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]urea;

(136) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(2-trifluoromethylphenyl)acetyl]urea;

(137) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(2-trifluoromethyl)acetyl]urea;

(138) 1-[2-(2,3-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]urea;

(139) 1-[2-(2,3-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]urea;

(140) 1-[2-(3,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]urea;

(141) 1-[2-(3,5-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]urea;

(142) 1-[2-(3,5-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]urea;

(147) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-(3-methylsulfanylpropionyl)thiourea;

(148) 1-(4-chloro-butyryl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]thiourea;

(149) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(2-o-tolylacetyl)thiourea;

(151) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2-fluorophenyl)acetyl]thiourea;

(152) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2-fluorophenyl)acetyl]thiourea;

(153) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2-methoxyphenyl)acetyl]thiourea;

(154) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2-methoxyphenyl)acetyl]thiourea;

(155) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2-nitrophenyl)acetyl]thiourea;

(156) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2-nitrophenyl)acetyl]thiourea;

(157) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(2-phenoxyacetyl)thiourea;

(158) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-phenylpropionyl)thiourea;

(159) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(3-ethoxypropionyl)thiourea;

(161) 1-(3-cyclopentylpropionyl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]thiourea;

(162) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-methylphenyl]-3-phenylacetylthiourea;

(163) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2,5-dimethylphenyl]-3-phenylacetylthiourea;

(164) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(3-fluorophenyl)acetyl]thiourea;

(165) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-(3-ethoxypropionyl)thiourea;

(166) 1-(2-cyclohexylacetyl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluorophenyl]thiourea;

(167) 1-(2-butoxyacetyl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]thiourea;

(168) 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-3-(2-p-tolylacetyl)thiourea;

(169) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(2-methoxyphenyl)acetyl]thiourea;

(170) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-(2-o-tolylacetyl)thiourea;

(171) 1-[2-(3-chlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]thiourea;

(172) 1-[2-(3-chlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(173) 1-[2-(3-chlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(174) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(3-chlorophenyl)acetyl]thiourea;

(175) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-(2-m-tolylacetyl)thiourea;

(176) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-(2-m-tolylacetyl)thiourea;

(180) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-(3-methoxy-propionyl)thiourea;

(181) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(3-methoxyphenyl)acetyl]thiourea;

(182) 1-[2-(2-chlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(183) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2-chlorophenyl)acetyl]thiourea;

(184) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(3-methoxyphenyl)acetyl]thiourea;

(185) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(3-methoxyphenyl)acetyl]thiourea;

(186) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(3-methoxyphenyl)acetyl]thiourea;

(187) 1-[2-(4-chlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]thiourea;

(188) 1-[2-(4-chlorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(189) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(4-chlorophenyl)acetyl]thiourea;

(190) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-(2-p-tolylacetyl)thiourea;

(191) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(4-methyl-cyclohexyl)acetyl]thiourea;

(192) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(4-methyl-cyclohexyl)acetyl]thiourea;

(193) 1-(2-butoxyacetyl)-3-[3-chloro-4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]thiourea;

(194) 1-[2-(2,3-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(195) 1-[2-(2,5-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(196) 1-[2-(3,5-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(197) 1-[2-(3,5-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(198) 1-[2-(3,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(199) 1-[2-(3,4-difluorophenyl)acetyl]-3-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]thiourea;

(200) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(2-trifluoromethylphenyl)acetyl]-thiourea;

(201) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(2-trifluoromethylphenyl)acetyl]-thiourea;

(202) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(3-trifluoromethylphenyl)acetyl]-thiourea;

(203) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(3-trifluoromethylphenyl)acetyl]-thiourea;

(204) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2,3,6-trifluorophenyl)acetyl]-thiourea;

(205) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-3-[2-(2,3,6-trifluorophenyl)acetyl]-thiourea;

(206) 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-3-[2-(2,3,6-trifluorophenyl)acetyl]-thiourea;

(207) 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-3-[2-(2,3,6-trifluorophenyl)acetyl]-thiourea;

(208) 1-[2-(2,6-dichlorophenyl)acetyl]-3-[4-(,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]thiourea;

(209) N-butyl-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(210) N-(3-chlorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(211) N-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-N′-(2-methoxyphenyl)malonamide;

(212) N-cyclobutyl-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(213) methyl 3-{2-[4-(6,7-dimethoxyquinolin-4-yloxy)phenylcarbamoyl]acetylamino}benzoate;

(214) N-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-N′-(1-phenylethyl)malonamide;

(215) N-benzyl-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(216) N-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]-N′-methyl-N′-phenylmalonamide;

(217) N-cyclohexyl-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(218) N-cyclohexylmethyl-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(219) N-(4-chlorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)phenyl]malonamide;

(220) N-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-N′-(3-hydroxyphenyl)malonamide;

(221) N-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-N′-(3,3-dimethyl-butyl)malonamide;

(222) N-[2-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-N′-(2,4-difluorophenyl)malonamide;

(223) N-(2,4-difluorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-methylphenyl]malonamide;

(224) N-(2,4-difluorophenyl)-N′-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2,5-dimethylphenyl]malonamide;

(225) N-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-2-methyl-N′-phenylmalonamide;

(226) N-cyclohexyl-N′-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-2-methylmalonamide;

(227) N-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-N′-pyridin-3-ylmalonamide;

(228) N-[4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-2,2-dimethyl-N′-phenylmalonamide;

(229) N-(2,4-difluorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(230) N-(3-bromo-5-methyl-2-pyridyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(231) N-(5-chloro-2-pyridyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(232) N-(5-methyl-3-isoxazolyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(233) N-(3-methyl-2-pyridyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(234) N-(6-methyl-2-pyridyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(235) N-(5-methyl-2-pyridyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(236) N-(2-pyridyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(237) N-(1-methyl-1H-5-pyrazolyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(238) N-(2,3-dihydro-1,4-benzodioxin-6-yl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(239) N-(3-cyanophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(240) N-[2-(trifluoromethyl)phenyl]-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)methan-amide;

(241) N-[4-(cyanomethyl)phenyl]-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(242) N-(4-chloro-2-methylphenyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(243) N-(2,3-dihydro-1H-5-indenyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(244) N-(3-methoxyphenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(245) methyl 2-({({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)carbonyl}amino)benzoate;

(246) N-(2-benzylphenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(247) N-(2-bromophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(248) N-(2-chlorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(249) N-(4-chlorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(250) N-(2-chloro-4-fluorophenyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(251) N-(3-fluorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(252) N-(2-fluorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(253) N-[2-(methylsulfanyl)phenyl]-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(254) N-(4-nitrophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(255) N-(2-phenoxyphenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(256) N-(3-methylphenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(257) N-(4-methylphenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(258) N-(2,6-dimethylphenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(259) N-[2-(1H-1-pyrrolyl)phenyl]-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(260) N-(8-quinolyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(261) N-(3-acetylphenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(262) N-(5-quinolyl)-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(263) N-(2,6-dichlorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(264) N-(3,4-difluorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(265) N-(2,6-difluorophenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(266) N-(2-methoxyphenyl)-({[4-(6,7-dimethoxy-quinolin-4-yloxy)anilino]carbonyl}amino)methanamide;

(267) N-[2-(2-hydroxyethyl)phenyl]-({[4-(6,7-dimethoxyquinolin-4-yloxy)anilino]carbonyl}amino)-methanamide;

(268) N-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)quinolin-4-yloxy]phenyl}-N′-phenylacetyl-thiourea;

(269) N-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)quinolin-4-yloxy]phenyl}-N′-(4-fluorophenyl)-malonamide;

(270) 1-(3-fluoro-4-{6-methoxy-7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-quinolin-4-yloxy}-phenyl)-3-phenylacetyl-thiourea;

(271) 1-(3-fluoro-4-{6-methoxy-7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-quinolin-4-yloxy}-phenyl)-3-[2-(4-fluorophenyl)-acetyl]-thiourea;

(272) 1-{4-[7-(2-diethylamino-ethoxy)-6-methoxy-quinolin-4-yloxy]-3-fluorophenyl}-3-phenylacetylthio-urea;

(273) 1-(3-fluoro-4-{6-methoxy-7-[2-(4-methyl-[1,4]diazepan-1-yl)-ethoxy]-quinolin-4-yloxy}-phenyl)-3-phenylacetyl-thiourea;

(275) 1-{4-[7-(2-diethylamino-ethoxy)-6-methoxy-quinolin-4-yloxy]-3-fluorophenyl}-3-[2- 9 2-(4-fluoro-phenyl)-acetyl]thiourea;

(276) 1-{3-fluoro-4-[6-methoxy-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-thiourea;

(277) 1-{3-fluoro-4-[6-methoxy-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(4-fluorophenyl)-acetyl]-thiourea;

(278) 1-{3-fluoro-4-[6-methoxy-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(2-fluorophenyl)-acetyl]-thiourea;

(279) 1-{3-fluoro-4-[6-methoxy-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(3-fluorophenyl)-acetyl]-thiourea;

(282) 1-(3-fluoro-4-{7-[2-(4-hydroxymethyl-piperidin-1-yl)-ethoxy]-6-methoxy-quinolin-4-yloxy}-phenyl)-3-[2-(4-fluoro-phenyl)-acetyl]-thiourea;

(283) 1-(3-fluoro-4-{7-[2-(4-hydroxymethyl-piperidin-1-yl)-ethoxy]-6-methoxy-quinolin-4-yloxy}-phenyl)-3-phenylacetylurea;

(284) 1-(3-fluoro-4-{7-[2-(4-hydroxymethyl-piperidin-1-yl)-ethoxy]-6-methoxy-quinolin-4-yloxy}-phenyl)-3-phenylacetyl-thiourea;

(285) 1-[2-(2-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-thiourea;

(286) 1-{2-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(4-fluorophenyl)-acetyl]-urea;

(287) 1-{2-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-phenyl-acetyl-urea;

(288) 1-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(2-fluoro-phenyl)-acetyl]-thiourea;

(289) 1-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(3-fluoro-phenyl)-acetyl]-thiourea;

(291) 1-{4-[7-(3-diethylamino-propoxy)-6-methoxy-quinolin-4-yloxy]-3-fluoro-phenyl}-3-phenylacetyl-urea;

(292) 1-{3-fluoro-4-[6-methoxy-7-(3-pyrrolidin-1-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-urea;

(293) 1-{4-[7-(3-diethylamino-propoxy)-6-methoxy-quinolin-4-yloxy]-3-fluorophenyl}

(294) 1-{3-fluoro-4-[6-methoxy-7-(3-pyrrolidin-1-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(2-fluoro-phenyl)-acetyl]-urea;

(295) 1-{3-fluoro-4-[6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(2-fluorophenyl)-acetyl]-urea;

(296) 1-(3-fluoro-4-{6-methoxy-7-[3-(4-methyl-piperazin-1-yl)-propoxy]-quinolin-4-yloxy}-phenyl)-3-[2-(2-fluorophenyl)-acetyl]-urea;

(297) 1-(3-fluoro-4-{6-methoxy-7-[3-(4-methyl-piperazin-1-yl)-propoxy]-quinolin-4-yloxy}-phenyl)-3-(2-m-toluyl-acetyl)-thiourea;

(298) 1-{3-chloro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(2-fluoro-phenyl)-acetyl]-thiourea;

(299) 1-{3-chloro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-[2-(3-fluoro-phenyl)-acetyl]-thiourea;

(300) 1-{3-chloro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-thiourea;

(301) 1-{3-chloro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-(2-o-toluyl-acetyl)-thiourea;

(302) 1-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-(2-o-toluyl-acetyl)-thiourea;

(303) 1-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-(2-m-toluyl-acetyl)-thiourea;

(304) 1-{3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-3-(2-p-toluyl-acetyl)-thiourea;

(305) 1-{3-fluoro-4-[7-(3-imidazol-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]phenyl}-3-phenylacetyl-urea;

(306) 1-{3-fluoro-4-[7-(3-imidazol-1-yl-propoxy)-6-methoxy-quinolin-4yloxy]-phenyl}-3-[2-(2-fluoro-phenyl)-acetyl]-urea;

(307) 1-{3-fluoro-4-[7-(3-imidazol-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-thiourea;

(308) 1-(3-fluoro-4-{7-[3-(4-hydroxymethyl-piperidin-1-yl)-propoxy]-6-methoxy-quinolin-4-yloxy}-phenyl)-3-phenylacetyl-urea;

(309) 1-(3-fluoro-4-{7-[3-(4-hydroxymethyl-piperidin-1-yl)-propoxy]-6-methoxy-quinolin-4-yloxy}-phenyl)-3-phenylacetyl-thiourea;

(310) 1-(3-fluoro-4-{7-[3-(4-hydroxymethyl-piperidin-1-yl)-propoxy]-6-methoxy-quinolin-4-yloxy}-phenyl)-3-[2-(4-fluorophenyl)-acetyl]-thiourea;

(311) 1-(2-fluoro-4-{7-[3-(4-hydroxymethyl-piperidin-1-yl)-propoxy]-6-methoxy-quinolin-4-yloxy}-phenyl)-3-phenylacetyl-urea;

(312) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-4-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-thiourea;

(313) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-4-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-thiourea;

(314) 1-[2-(2-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-4-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(315) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-4-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-[2-(2-fluoro-phenyl)-acetyl]-thiourea;

(316) 1-[2-(2-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-piperidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(317) 1-[2-(2-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(318) 1-{3-fluoro-4-[7-(2-hydroxy-3-piperidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-[2-(2-fluoro-phenyl)-acetyl]-thiourea;

(319) 1-{3-fluoro-4-[7-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-[2-(2-fluoro-phenyl)-acetyl]-thiourea;

(320) 1-[2-(3-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-4-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(321) 1-[2-(3-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-piperidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(322) 1-[2-(3-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(323) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-4-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-[2-(3-fluoro-phenyl)-acetyl]-thiourea;

(324) 1-{3-fluoro-4-[7-(2-hydroxy-3-piperidin-1-yl-propoxy)-6-methoxy-quinolin-4yloxy]-phenyl}-3-[2-(3-fluoro-phenyl)-acetyl]-thiourea;

(325) 1-{3-fluoro-4-[7-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-[2-(3-fluoro-phenyl)-acetyl]-thiourea;

(326) 1-[2-(4-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-4-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(327) 1-[2-(4-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-piperidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(328) 1-[2-(4-chloro-phenyl)-acetyl]-3-{3-fluoro-4-[7-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-thiourea;

(329) 1-{3-fluoro-4-[7-(2-hydroxy-3-piperidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-[2-(4-fluoro-phenyl)-acetyl]-thiourea;

(330) 1-{3-fluoro-4-[7-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-[2-(4-fluoro-phenyl)-acetyl]-thiourea;

(331) 1-{3-fluoro-4-[7-(2-hydroxy-3-piperidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-(2-phenylacetyl)-thiourea;

(332) 1-{3-fluoro-4-[7-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-(2-phenylacetyl)-thiourea;

(333) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-(2-o-toluyl-acetyl)-thiourea;

(334) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-(2-m-toluyl-acetyl)-thiourea;

(335) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-(2-p-toluyl-acetyl)-thiourea;

(336) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-1-yl-propoxy)-6-methoxy-quinolin-4yloxy]-phenyl}-3-[2-(4-fluoro-phenyl)-acetyl]-urea; and

(337) 1-{3-fluoro-4-[7-(2-hydroxy-3-morpholin-1-yl-propoxy)-6-methoxy-quinolin-4-yloxy]-phenyl}-3-(2-phenylacetyl)-urea.

17. The method according to claim 9 , wherein R 103 represents C 1-4 alkoxy.

18. The method according to claim 9 , wherein R 103 represents methoxy.

19. The method according to claim 9 , wherein R 105 , R 106 , R 107 , and R 108 , which may be the same or different, represents a hydrogen or C 1-4 alkoxy.

20. The method according to claim 9 , wherein R 105 , R 106 , R 107 , and R 108 , which may be the same or different, represents a hydrogen or methoxy.

21. The method according to claim 9 , wherein R 105 represents methoxy, R 106 , R 107 , and R 108 represent a hydrogen atom.

22. The method according to claim 9 , wherein R 109 represents C 1-6 alkyl substituted by —R 114 ; R 114 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted.

23. The method according to claim 9 , wherein R 109 represents C 1-6 alkyl substituted by —R 114 ; R 114 represents optionally substituted phenyl.

24. The method according to claim 9 , wherein R 109 represents methyl substituted by —R 114 ; R 114 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted.

25. The method according to claim 9 , wherein R 109 represents methyl substituted by —R 114 ; R 114 represents optionally substituted phenyl.

26. The method according to claim 9 , wherein R 109 represents C 1-6 alkyl substituted by —R 114 ; R 114 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted by a halogen atom.

27. The method according to claim 9 , wherein R 109 represents C 1-6 alkyl substituted by —R 114 ; R 114 represents phenyl optionally substituted by a halogen atom.

28. The method according to claim 9 , wherein R 109 represents methyl substituted by —R 114 ; R 114 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted by a halogen atom.

29. The method according to claim 9 , wherein R 109 represents methyl substituted by —R 114 ; R 114 represents phenyl optionally substituted by a halogen atom.

30. The method according to claim 9 , wherein R 109 represents C 1-6 alkyl substituted by —R 114 ; R 114 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted by a fluorine atom.

31. The method according to claim 9 , wherein R 109 represents C 1-6 alkyl substituted by —R 114 ; R 114 represents phenyl which is optionally substituted by a fluorine atom.

32. The method according to claim 9 , wherein R 109 represents methyl substituted by —R 114 ; R 114 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted by a fluorine atom.

33. The method according to claim 9 , wherein R 109 represents methyl substituted by —R 114 ; R 114 represents phenyl which is optionally substituted by a fluorine atom.

34. The method according to claim 9 , wherein R 103 represents C 1-4 alkoxy which is substituted by a saturated or unsaturated five- to seven-membered heterocyclic group which is optionally substituted by C 1-6 alkyl.

35. The method according to claim 9 , wherein R 103 represents C 3 alkoxy which is substituted by a saturated six-membered heterocyclic group.

36. The method according to claims 34 or 35 , wherein R 105 , R 106 , R 107 , and R 108 , which may be the same or different, represents a hydrogen or a halogen atom.

37. The method according to claims 34 or 35 , wherein R 105 represents a halogen atom, R 106 , R 107 , and R 108 represent a hydrogen atom.

38. The method according to claims 34 or 35 , wherein R 106 represents a halogen atom, R 105 , R 107 , and R 108 represent a hydrogen atom.

39. The method according to any one of claims 34 or 35 , wherein R 109 represents C 1 alkyl substituted by —R 114 ; R 114 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring, when the three- to eight-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form a C 1-3 alkylene chain, or the three-to eight-membered carbocyclic or heterocyclic group may be a bicyclic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group.

40. The method according to any one of claims 34 or 35 , wherein R 109 represents C 1 alkyl substituted by —R 114 ; R 114 represents phenyl which is optionally substituted by a halogen atom.

41. The method according to claim 11 , wherein R 203 represents C 1-4 alkoxy which is optionally substituted by a saturated or unsaturated five- to seven-membered heterocyclic group which is optionally substituted by C 1-6 alkyl.

42. The method according to claim 11 , wherein R 203 represents C 1 alkoxy.

43. The method according to any one of claims 11 , 41 or 42 , wherein R 205 , R 206 , R 207 , and R 208 , which may be the same or different, represents a hydrogen or a halogen atom.

44. The method according to any one of claims 11 , 41 or 42 , wherein R 205 represents a halogen atom, R 206 , R 207 , and R 208 represent a hydrogen atom.

45. The method according to any one of claims 11 , 41 or 42 , wherein R 206 represents a halogen atom, R 205 , R 207 , and R 208 represent a hydrogen atom.

46. The method according to any one of claims 11 , 41 , or 42 , wherein R 209 represents C 1 alkyl substituted by —R 214 ; R 214 represents a saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group which is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy, a halogen atom, nitro, trifluoromethyl, C 1-6 alkoxy carbonyl, cyano, cyano C 1-6 alkyl, C 1-6 alkylthio, phenoxy, acetyl, or a saturated or unsaturated five- or six-membered heterocyclic ring, when the three- to eight-membered carbocyclic or heterocyclic group is substituted by two C 1-6 alkyl groups, the two alkyl groups may combine together to form a C 1-3 alkylene chain, or the three-to eight-membered carbocyclic or heterocyclic group may be a bicyclic group condensed with another saturated or unsaturated three- to eight-membered carbocyclic or heterocyclic group.

47. The method according to any one of claims 11 , 41 or 42 , wherein R 209 represents C 1 alkyl substituted by —R 214 ; R 214 represents phenyl which is optionally substituted by a halogen atom.