ANTITUMOR AGENT FOR UNDIFFERENTIATED GASTRIC CANCER

• US 20090264464A1
• Filed: 08/27/2007
• Published: 10/22/2009
• Est. Priority Date: 08/28/2006
• Status: Active Grant

• Current Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Original Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Inventors: Nakagawa, Takayuki, Matsushima, Tomohiro, Obaishi, Hiroshi, Yamamoto, Yuji, Tsuruoka, Akihiko
• Granted Patent: US 8,865,737 B2
• Time in Patent Office: Days
• US Class Current: 514/312
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 215/22 attached in position 2 or 4
• CPC Class Codes: C07D 215/48 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57446 of stomach or intestine

Abstract

The present invention relates to a therapeutic agent represented by the General formula (I), or a pharmacologically acceptable salt thereof, or a solvate of the compound or the salt thereof:

The therapeutic agent comprises a substance having the activity of inhibiting kinase activity of fibroblast growth factor receptor 2 (“FGFR2”). The therapeutic agent can be used for treating undifferentiated gastric cancer, and can also be used to treat organisms comprising a cell overexpressing FGFR2 or a cell expressing mutant FGFR2, or both. The present invention further relates to a pharmaceutical composition comprising an FGFR2 inhibitory and methods of treatment therewith. The present invention also relates to a method for predicting the effect of an FGFR2 inhibitory substance on a patient.

Claims

1. :

A therapeutic agent for treating undifferentiated gastric cancer, comprising a compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof;

2. :

A therapeutic agent according to claim 1, wherein R¹ is a C_1-6 alkyl group (provided that R¹ may have at least one substituent selected from the group consisting of a 3-10-membered nonaromatic heterocyclic group, a hydroxyl group, a C_1-6 alkoxy group, an amino group, a mono-C_1-6 alkylamino group and a di-C_1-6 alkylamino group which may have a C_1-6 alkyl group).

3. :

A therapeutic agent according to claim 1, wherein R¹ is a methyl group or a group represented by any one of the following formulae

4. :

A therapeutic agent according to claim 1, wherein R¹ is a methyl group or a 2-methoxyethyl group.

5. :

A therapeutic agent according to claim 1, wherein R² is a cyano group or a group represented by Formula —

CONV^a11V^a12 (wherein, V^a11 represents a hydrogen atom, an optionally substituted C_1-6 alkyl group, an optionally substituted C_2-6 alkenyl group, an optionally substituted C_2-6 alkynyl group, an optionally substituted C_3-8 cycloalkyl group, an optionally substituted C_6-10 aryl group, an optionally substituted 5-10-membered heteroaryl group or an optionally substituted 3-10-membered nonaromatic heterocyclic group;

V^a12 represents a hydrogen atom, an optionally substituted C_1-6 alkyl group, an optionally substituted C_2-6 alkenyl group, an optionally substituted C_2-6 alkynyl group, an optionally substituted C_3-8 cycloalkyl group, an optionally substituted C_6-10 aryl group, an optionally substituted 5-10-membered heteroaryl group, an optionally substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl group, an optionally substituted C_1-6 alkoxy group or an optionally substituted C_3-8 cycloalkoxy group).

6. :

A therapeutic agent according to claim 1, wherein R² is a cyano group or a group represented by Formula —

CONHV^a16 (wherein, V^a16 represents a hydrogen atom, a C_1-6 alkyl group, a C_3-8 cycloalkyl group, a C_1-6 alkoxy group or a C_3-8 cycloalkoxy group, provided that V^a16 may have at least one substituent selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C_1-6 alkoxy group).

7. :

A therapeutic agent according to claim 1, wherein R² is a group represented by Formula —

CONHV^a17 (wherein, V^a17 represents a hydrogen atom, a C_1-6 alkyl group or a C_1-6 alkoxy group).

8. :

A therapeutic agent according to claim 1, wherein R² is a group represented by Formula —

CONHV^a18 (wherein, V^a18 represents a hydrogen atom, a methyl group or a methoxy group).

9. :

A therapeutic agent according to claim 1, wherein Y¹ is a group represented by the following formula

10. :

A therapeutic agent according to claim 1, wherein R³ and R⁴ are hydrogen atoms.

11. :

A therapeutic agent according to claim 1, wherein R⁵ is a hydrogen atom, a C_1-6 alkyl group, a C_3-8 cycloalkyl group or a C_6-10 aryl group (provided that R⁵ may have at least one substituent selected from the group consisting of a halogen atom and a methanesulfonyl group).

12. :

A therapeutic agent according to claim 1, wherein R⁵ is a methyl group, an ethyl group or a cyclopropyl group.

13. :

A therapeutic agent according to claim 1, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is at least one compound selected from the group consisting of;

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′

-(4-fluorophenyl)urea;

N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′

-cyclopropylurea;

N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′

-(4-fluorophenyl)urea;

N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′

-(4-fluorophenyl)urea;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;

4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;

4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′

-cyclopropylurea;

N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′

-cyclopropylurea;

N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′

-(3-(methylsulfonyl)phenyl)urea;

4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide; and

N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′

-cyclopropylurea,

a pharmacologically acceptable salt thereof or a solvate thereof.

14. :

A therapeutic agent according to claim 1, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is at least one compound selected from the group consisting of;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide; and

N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,

a pharmacologically acceptable salt thereof or a solvate thereof.

15. :

A therapeutic agent according to claim 1, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, a pharmacologically acceptable salt thereof or a solvate thereof.

16. :

A therapeutic agent according to claim 1, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is methanesulfonate of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.

18. :

A therapeutic agent according to claim 1, wherein the undifferentiated gastric cancer comprises at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2.

19. :

A therapeutic agent according to claim 18, wherein the mutant FGFR2 comprises a mutation site where an amino acid sequence downstream from at least position 813 is deleted in amino acids 22-822 of the amino acid sequence represented by SEQ ID NO;

2, or a mutation site where an amino acid sequence downstream from at least position 812 is deleted in amino acids 22-821 of the amino acid sequence represented by SEQ ID NO;

4.

20. :

A therapeutic agent according to claim 1, wherein the undifferentiated gastric cancer is at least one gastric cancer selected from the group consisting of poorly differentiated adenocarcinoma, signet-ring cell carcinoma, mucinous carcinoma and scirrhous gastric cancer.

17. :

A therapeutic agent for treating undifferentiated gastric cancer, comprising at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl] indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea, a pharmacologically acceptable salt thereof or a solvate thereof.

21. :

A pharmaceutical composition to be administered to an organism comprising at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2, the pharmaceutical composition comprising a compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof;

22. :

A pharmaceutical composition according to claim 21, wherein R¹ is a C_1-6 alkyl group (provided that R¹ may have at least one substituent selected from the group consisting of a 3-10-membered nonaromatic heterocyclic group, a hydroxyl group, a C_1-6 alkoxy group, an amino group, a mono-C_1-6 alkylamino group and a di-C_1-6 alkylamino group which may have a C_1-6 alkyl group).

23. :

A pharmaceutical composition according to claim 21, wherein R¹ is a methyl group or a group represented by any one of the following formulae

24. :

A pharmaceutical composition according to claim 21, wherein R¹ is a methyl group or a 2-methoxyethyl group.

25. :

A pharmaceutical composition according to claim 21, wherein R² is a cyano group or a group represented by Formula —

CONV^a11V^a12 (wherein, V^a11 represents a hydrogen atom, an optionally substituted C_1-6 alkyl group, an optionally substituted C_2-6 alkenyl group, an optionally substituted C_2-6 alkynyl group, an optionally substituted C_3-8 cycloalkyl group, an optionally substituted C_6-10 aryl group, an optionally substituted 5-10-membered heteroaryl group or an optionally substituted 3-10-membered nonaromatic heterocyclic group;

V^a12 represents a hydrogen atom, an optionally substituted C_1-6 alkyl group, an optionally substituted C_2-6 alkenyl group, an optionally substituted C_2-6 alkynyl group, an optionally substituted C_3-8 cycloalkyl group, an optionally substituted C_6-10 aryl group, an optionally substituted 5-10-membered heteroaryl group, an optionally substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl group, an optionally substituted C_1-6 alkoxy group or an optionally substituted C_3-8 cycloalkoxy group).

26. :

A pharmaceutical composition according to claim 21, wherein R² is a cyano group or a group represented by Formula —

CONHV^a16 (wherein, V^a16 represents a hydrogen atom, a C_1-6 alkyl group, a C_3-8 cycloalkyl group, a C_1-6 alkoxy group or a C_3-8 cycloalkoxy group, provided that V^a16 may have at least one substituent selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C_1-6 alkoxy group).

27. :

A pharmaceutical composition according to claim 21, wherein R² is a group represented by Formula —

CONHV^a17 (wherein, V^a17 represents a hydrogen atom, a C_1-6 alkyl group or a C_1-6 alkoxy group).

28. :

A pharmaceutical composition according to claim 21, wherein R² is a group represented by Formula —

CONHV^a18 (wherein, V^a18 represents a hydrogen atom, a methyl group or a methoxy group).

29. :

A pharmaceutical composition according to claim 21, wherein Y¹ is a group represented by the following formula

30. :

A pharmaceutical composition according to claim 21, wherein R³ and R⁴ are hydrogen atoms.

31. :

A pharmaceutical composition according to claim 21, wherein R⁵ is a hydrogen atom, a C_1-6 alkyl group, a C_3-8 cycloalkyl group or a C_6-10 aryl group (provided that R⁵ may have at least one substituent selected from the group consisting of a halogen atom and a methanesulfonyl group).

32. :

A pharmaceutical composition according to claim 21, wherein R⁵ is a methyl group, an ethyl group or a cyclopropyl group.

33. :

A pharmaceutical composition according to claim 21, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is at least one compound selected from the group consisting of;

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′

-(4-fluorophenyl)urea;

N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′

-cyclopropylurea;

N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′

-(4-fluorophenyl)urea;

N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′

-(4-fluorophenyl)urea;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;

4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(ethyl)aminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;

4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′

-cyclopropylurea;

N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′

-cyclopropylurea;

N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′

-(3-(methylsulfonyl)phenyl)urea;

4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide; and

N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′

-cyclopropylurea,

a pharmacologically acceptable salt thereof or a solvate thereof.

34. :

A pharmaceutical composition according to claim 21, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is at least one compound selected from the group consisting of;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide; and

N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,

a pharmacologically acceptable salt thereof or a solvate thereof.

35. :

A pharmaceutical composition according to claim 21, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, a pharmacologically acceptable salt thereof or a solvate thereof.

36. :

A pharmaceutical composition according to claim 21, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is methanesulfonate of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.

38. :

A pharmaceutical composition according to claim 21, wherein the mutant FGFR2 comprises a mutation site where an amino acid sequence downstream from at least position 813 is deleted in amino acids 22-822 of the amino acid sequence represented by SEQ ID NO;

2, or a mutation site where an amino acid sequence downstream from at least position 812 is deleted in amino acids 22-821 of the amino acid sequence represented by SEQ ID NO;

4.

39. :

A pharmaceutical composition according to claim 21, wherein the organism is a patient suffering from undifferentiated gastric cancer.

40. :

A pharmaceutical composition according to claim 39, wherein the undifferentiated gastric cancer is at least one gastric cancer selected from the group consisting of poorly differentiated adenocarcinoma, signet-ring cell carcinoma, mucinous carcinoma and scirrhous gastric cancer.

37. :

A pharmaceutical composition to be administered to an organism comprising at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2, the pharmaceutical composition comprising at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof.

41. :

A method for treating undifferentiated gastric cancer, characterized by administering an effective dosage of a compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof to a patient;

42. :

A method for treating undifferentiated gastric cancer, characterized by administering an effective dosage of at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof to a patient.

43. :

A method for treating a disease, characterized by administering an effective dosage of a compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof to an organism comprising at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2;

44. :

A method for treating a disease, characterized by administering an effective dosage of at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof to an organism comprising at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2.

45. :

Use of a compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof for producing a therapeutic agent for treating undifferentiated gastric cancer;

46. :

Use of at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof for producing a therapeutic agent for treating undifferentiated gastric cancer.

47. :

Use of a compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof for producing a pharmaceutical composition to be administered to an organism comprising at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2;

48. :

Use of at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl] indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof for producing a pharmaceutical composition to be administered to an organism comprising at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2.

49. :

A compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof for a therapeutic agent for treating undifferentiated gastric cancer;

General Formula (I)

50. :

At least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof for a therapeutic agent for treating undifferentiated gastric cancer.

51. :

A compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof for a pharmaceutical composition to be administered to an organism comprising at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2;

52. :

At least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof for a pharmaceutical composition to be administered to an organism comprising at least one selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2.

53. :

A FGFR2 inhibitor comprising a compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof;

54. :

A FGFR2 inhibitor comprising at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof.

55. :

A method for predicting whether or not a patient is highly sensitive to a compound represented by the following General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof, by using at least one selected from the group consisting of an expression level of FGFR2 and the presence or the absence of FGFR2 mutation in the cell as a biomarker;

56. :

A method according to claim 55, wherein R¹ is a C_1-6 alkyl group (provided that R¹ may have at least one substituent selected from the group consisting of a 3-10-membered nonaromatic heterocyclic group, a hydroxyl group, a C_1-6 alkoxy group, an amino group, a mono-C_1-6 alkylamino group and a di-C_1-6 alkylamino group which may have a C_1-6 alkyl group).

57. :

A method according to claim 55, wherein R¹ is a methyl group or a group represented by any one of the following formulae

58. :

A method according to claim 55, wherein R¹ is a methyl group or a 2-methoxyethyl group.

59. :

A method according to claim 55, wherein R² is a cyano group or a group represented by Formula —

CONV^a11V^a12 (wherein, V^a11 represents a hydrogen atom, an optionally substituted C_1-6 alkyl group, an optionally substituted C_2-6 alkenyl group, an optionally substituted C_2-6 alkynyl group, an optionally substituted C_3-8 cycloalkyl group, an optionally substituted C_6-10 aryl group, an optionally substituted 5-10-membered heteroaryl group or an optionally substituted 3-10-membered nonaromatic heterocyclic group;

V^a12 represents a hydrogen atom, an optionally substituted C_1-6 alkyl group, an optionally substituted C_2-6 alkenyl group, an optionally substituted C_2-6 alkynyl group, an optionally substituted C_3-8 cycloalkyl group, an optionally substituted C_6-10 aryl group, an optionally substituted 5-10-membered heteroaryl group, an optionally substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl group, an optionally substituted C_1-6 alkoxy group or an optionally substituted C_3-8 cycloalkoxy group).

60. :

A method according to claim 55, wherein R² is a cyano group or a group represented by Formula —

CONHV^a16 (wherein, V^a16 represents a hydrogen atom, a C_1-6 alkyl group, a C_3-8 cycloalkyl group, a C_1-6 alkoxy group or a C_3-8 cycloalkoxy group, provided that V^a16 may have at least one substituent selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C_1-6 alkoxy group).

61. :

A method according to claim 55, wherein R² is a group represented by Formula —

CONHV^a17 (wherein, V^a17 represents a hydrogen atom, a C_1-6 alkyl group or a C_1-6 alkoxy group).

62. :

A method according to claim 55, wherein R² is a group represented by Formula —

CONHV^a18 (wherein, V^a18 represents a hydrogen atom, a methyl group or a methoxy group).

63. :

A method according to claim 55, wherein Y¹ is a group represented by the following formula

64. :

A method according to claim 55, wherein R³ and R⁴ are hydrogen atoms.

65. :

A method according to claim 55, wherein R⁵ is a hydrogen atom, a C_1-6 alkyl group, a C_3-8 cycloalkyl group or a C_6-10 aryl group (provided that R⁵ may have at least one substituent selected from the group consisting of a halogen atom and a methanesulfonyl group).

66. :

A method according to claim 55, wherein R⁵ is a methyl group, an ethyl group or a cyclopropyl group.

67. :

A method according to claim 55, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is at least one compound selected from the group consisting of;

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′

-(4-fluorophenyl)urea;

N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′

-cyclopropylurea;

N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′

-(4-fluorophenyl)urea;

N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′

-(4-fluorophenyl)urea;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;

4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;

4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′

-cyclopropylurea;

N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;

4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;

N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′

-cyclopropylurea;

N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′

-(3-(methylsulfonyl)phenyl)urea;

4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide; and

N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′

-cyclopropylurea,

a pharmacologically acceptable salt thereof or a solvate thereof.

68. :

A method according to claim 55, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is at least one compound selected from the group consisting of;

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;

N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;

4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide; and

N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,

a pharmacologically acceptable salt thereof or a solvate thereof.

69. :

A method according to claim 55, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, a pharmacologically acceptable salt thereof or a solvate thereof.

70. :

A method according to claim 55, wherein the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof is methanesulfonate of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.

72. :

A method according to claim 55, wherein the FGFR2 mutation is deletion of an amino acid sequence downstream from at least position 813 in amino acids 22-822 of the amino acid sequence represented by SEQ ID NO;

2, or deletion of an amino acid sequence downstream from at least position 812 in amino acids 22-821 of the amino acid sequence represented by SEQ ID NO;

4.

73. :

A method according to claim 55, wherein the patient is a patient suffering from undifferentiated gastric cancer.

74. :

A method according to claim 73, wherein the undifferentiated gastric cancer is at least one gastric cancer selected from the group consisting of poorly differentiated adenocarcinoma, signet-ring cell carcinoma, mucinous carcinoma and scirrhous gastric cancer.

75. :

A method according to claim 55, wherein the method for predicting comprises the steps of;

determining at least one selected from the group consisting of an expression level of FGFR2 and the presence or the absence of FGFR2 mutation in the cell; and

predicting that the patient is highly sensitive to the compound represented by General Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof when FGFR2 is overexpressed or when mutant FGFR2 is expressed in the cell, or when both of the cases apply.

77. :

A method according to claim 75, wherein the determination of the presence or the absence of FGFR2 mutation in the cell is carried out by dideoxynucleotide chain termination technique.

78. :

A method according to claim 75, wherein the determination of the presence or the absence of FGFR2 mutation in the cell is carried out by RT-PCR.

79. :

A method according to claim 75, wherein the determination of the expression level of FGFR 2 in the cell or the determination of the presence or the absence of FGFR2 mutation in the cell is carried out by an immunochemical method.

71. :

A method for predicting whether or not a patient is highly sensitive to at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof where at least one selected from the group consisting of an expression level of FGFR2 and the presence or the absence of FGFR2 mutation in the cell is used as a biomarker.

76. :

A method according to claim 71, wherein the method for predicting comprises the steps of;

determining at least one selected from the group consisting of an expression level of FGFR2 and the presence or the absence of FGFR2 mutation in the cell; and

predicting that the patient is highly sensitive to at least one compound selected from the group consisting of;

N-(3-trifluoromethyl-4-chlorophenyl)-N′

-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea;

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole;

5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′

-(5-methyl-3-isoxazolyl)urea,

a pharmacologically acceptable salt thereof or a solvate thereof when FGFR2 is overexpressed or when mutant FGFR2 is expressed in the cell, or when both of the cases apply.

80. :

A method according to claim 76, wherein the determination of the presence or the absence of FGFR2 mutation in the cell is carried out by dideoxynucleotide chain termination technique.

81. :

A method according to claim 76, wherein the determination of the presence or the absence of FGFR2 mutation in the cell is carried out by RT-PCR.

82. :

A method according to claim 76, wherein the determination of the expression level of FGFR 2 in the cell or the determination of the presence or the absence of FGFR2 mutation in the cell is carried out by an immunochemical method.