Quinoline derivatives and quinazoline derivatives having azolyl group

1. A compound represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof:

wherein

X represents N,

Z represents CH;

Y represents O or S;

R 1 , R 2 , and R 3 , which may be the same or different, represent a hydrogen atom, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, nitro, or amino; wherein the C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, and C 2-6 alkynyl groups are optionally substituted by a halogen atom; hydroxyl; C 1-4 alkyl; C 1-4 alkoxycarbonyl; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl optionally substituted by hydroxyl or C 1-4 alkoxy; a group R 12 R 13 N—C(═O)—O— wherein R 12 and R 13 , which may be the same or different, represent a hydrogen atom or C 1-4 alkyl optionally substituted by hydroxyl or C 1-4 alkoxy; or a group R 14 —(S) m — wherein R 14 represents a saturated or unsaturated three- to seven-membered carbocyclic or heterocyclic group optionally substituted by C 1-4 alkyl and m is 0 or 1;

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, C 1-4 alkoxy, C 1-4 alkylthio, trifluoromethyl, nitro, or amino;

R 9 and R 10 , which may be the same or different, represent a hydrogen atom, C 1-6 alkyl, or C 1-4 alkylcarbonyl; wherein the alkyl portion of the C 1-6 alkyl or C 1-4 alkylcarbonyl group is optionally substituted by a halogen atom; C 1-4 alkoxy; amino optionally substituted by C 1-4 alkyl optionally substituted by C 1-4 alkoxy; or a saturated or unsaturated three- to seven-membered carbocyclic or heterocyclic group; and

R 11 represents azolyl on which one or more hydrogen atoms are optionally substituted by a halogen atom; C 1-4 alkyl; C 1-4 alkoxy; C 1-4 alkylthio; trifluoromethyl; nitro; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl group(s) which may be the same or different; C 1-4 alkoxycarbonyl C 1-4 alkyl, C 1-4 alkylcarbonyl, or C 3-5 cyclic alkyl.

2. The method according to claim 1 , wherein R 1 , R 9 , and R 10 represent a hydrogen atom.

3. The compound according to claim 1 , which is represented by formula (Ia):

wherein

X represents CH or N,

R 15 and R 16 , which may be the same or different, represent C 1-6 alkoxy,

R 17 , R 18 , R 19 , and R 20 , which may be the same or different, represent a hydrogen atom, a halogen atom, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylthio, trifluoromethyl, nitro, or amino,

R 21 represents azolyl on which one or more hydrogen atoms are optionally substituted by a halogen atom; C 1-4 alkyl; C 1-4 alkoxy; C 1-4 alkylthio; trifluoromethyl; nitro; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl group(s) which may be the same or different; C 1-4 alkoxycarbonyl C 1-4 alkyl; C 1-4 alkylcarbonyl; or C 3-5 cyclic alkyl.

4. The compound according to claim 3 , wherein R 15 and R 16 represent methoxy.

5. The compound according to claim 3 , wherein at least one of R 17 , R 18 , R 19 , and R 20 represents a halogen atom.

6. The compound according to claim 3 , wherein at least one of R 17 , R 18 , R 19 , and R 20 represents a chlorine or fluorine atom.

7. The compound according to claim 3 , wherein at least one of R 17 , R 18 , R 19 , and R 20 represents C 1-4 alkyl.

8. The compound according to claim 3 , wherein at least one of R 17 , R 18 , R 19 , and R 20 represents C 1-4 alkoxy.

9. The compound according to claim 3 , wherein at least one of R 17 , R 18 , R 19 , and R 20 represents C 1-4 alkylthio, trifluoromethyl, nitro, or amino.

10. The compound according to claim 3 , wherein R 21 represents group (i):

wherein Q represents O, S, or NH, and R 22 and R 23 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-4 alkyl; C 1-4 alkoxy; C 1-4 alkylthio; trifluoromethyl; nitro; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl group(s) which may be the same or different; C 1-4 alkoxycarbonyl C 1-4 alkyl; C 1-4 alkylcarbonyl; or C 3-5 cyclic alkyl.

11. The compound according to claim 3 , wherein R 21 represents group (ii):

wherein Q represents O, S, or NH, and R 22 and R 23 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-4 alkyl; C 1-4 alkoxy; C 1-4 alkylthio; trifluoromethyl; nitro; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl group(s) which may be the same or different; C 1-4 alkoxycarbonyl C 1-4 alkyl; C 1-4 alkylcarbonyl; or C 3-5 cyclic alkyl.

12. The compound according to claim 3 , wherein R 21 represents group (iii):

wherein Q represents O, S, or NH, and R 22 and R 23 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-4 alkyl; C 1-4 alkoxy; C 1-4 alkylthio; trifluoromethyl; nitro; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl group(s) which may be the same or different; C 1-4 alkoxycarbonyl C 1-4 alkyl; C 1-4 alkylcarbonyl; or C 3-5 cyclic alkyl.

13. The compound according to claim 3 , wherein R 21 represents group (iv):

wherein Q represents O, S, or NH, and R 22 represents a hydrogen atom; a halogen atom; C 1-4 alkyl; C 1-4 alkoxy; C 1-4 alkylthio; trifluoromethyl; nitro; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl group(s) which may be the same or different; C 1-4 alkoxycarbonyl C 1-4 alkyl; C 1-4 alkylcarbonyl; or C 3-5 cyclic alkyl.

14. The compound according to claim 3 , wherein R 21 represents optionally substituted thiazolyl.

15. The compound according to claim 3 , wherein R 21 represents optionally substituted oxazolyl.

16. The compound according to claim 3 , wherein R 21 represents optionally substituted isothiazolyl.

17. The compound according to claim 3 , wherein R 21 represents optionally substituted isoxazolyl.

18. The compound according to claim 3 , wherein R 21 represents optionally substituted pyrazolyl.

19. The compound according to claim 3 , wherein R 21 represents optionally substituted 1,2,4-thiadiazolyl.

20. The compound according to claim 3 , wherein R 21 represents optionally substituted 1,2,4-oxadiazolyl.

21. The compound according to claim 3 , wherein R 21 represents optionally substituted 1,3,4-thiadiazolyl.

22. The compound according to claim 3 , wherein R 21 represents optionally substituted 1,3,4-oxadiazolyl.

23. The compound according to claim 1 , which is represented by formula (Ib):

wherein

MeO represents methoxy;

X represents N;

R 17 , R 18 , and R 19 , which may be the same or different, represent a hydrogen atom, a halogen atom, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylthio, trifluoromethyl, nitro, or amino; and

R 21 represents group (i), (ii),(iii), or (iv).

wherein Q represents O, S, or NH, and R 22 and R 23 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-4 alkyl; C 1-4 alkoxy; C 1-4 alkylthio; trifluoromethyl; nitro; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl group(s) which may be the same or different; C 1-4 alkoxycarbonyl C 1-4 alkyl; C 1-4 alkylcarbonyl; or C 3-5 cyclic alkyl.

24. The compound according to claim 23 , wherein R 21 represents group (iii) wherein Q represents S.

25. The compound according to claim 24 , wherein both R 22 and R 23 represent a hydrogen atom, or one of R 22 and R 23 represents a hydrogen atom and the other represents C 1-4 alkyl.

26. The compound according to claim 1 , wherein R 11 represents

wherein Q represents O, S, or NH, and R 22 and R 23 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-4 alkyl; C 1-4 alkoxy; C 1-4 alkylthio; trifluoromethyl; nitro; amino on which one or two hydrogen atoms are optionally substituted by C 1-4 alkyl group(s) which may be the same or different; C 1-4 alkoxycarbonyl C 1-4 alkyl; C 1-4 alkylcarbonyl; or C 3-5 cyclic alkyl.

27. A compound selected from the group consisting of:

N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenyl}-N′-(5-methyl-3-isoxazolyl)urea;

N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenyl}-N′-(3-methyl-5-isoxazolyl)urea;

N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea;

N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(3-methyl-5-isoxazolyl)urea;

N-{3-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea;

N-{3-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(3-methyl-5-isoxazolyl)urea;

N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenyl}-N′-(3-methyl-5-isothiazolyl)urea;

N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(3-methyl-5-isothiazolyl)-urea;

N-{3-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(3-methyl-5-isothiazolyl)-urea;

N-{2-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(1,3-thiazol-2-yl)urea;

N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(5-methyl-1,3-thiazol-2-yl)urea;

N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(4,5-dimethyl-1,3-thiazol-2-yl)urea;

N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(4-methyl-1,3-thiazol-2-yl)urea;

N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenyl}-N′-(1,3-thiazol-2-yl)urea;

N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenyl}-N′-(5-methyl-1,3-thiazol-2-yl)urea;

N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenyl}-N′-(4-methyl-1,3-thiazol-2-yl)urea;

N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenyl}-N′-(4,5-dimethyl-1,3-thiazol-2-yl)urea;

N-{3-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(1,3-thiazol-2-yl)urea;

N-{3-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(5-methyl-1,3-thiazol-2-yl)urea;

N-{3-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(4-methyl-1,3-thiazol-2-yl)urea; and

N-{3-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(4,5-dimethyl-1,3-thiazol-2-yl)urea;

or a pharmaceutically acceptable salt or solvate thereof.

28. A pharmaceutical composition comprising the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof as active ingredient.

29. A method for treating a disease selected from the group consisting of a diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma, comprising:

administering to a mammal a therapeutically effective amount of at least one compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

30. A method for treating Kaposi's sarcoma comprising:

administering to a mammal a therapeutically effective amount of at least one compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

31. A method for treating colon cancer comprising:

administering to a mammal a therapeutically effective amount of at least one compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

32. A method for treating lung cancer comprising:

administering to a mammal a therapeutically effective amount of at least one compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

33. A method for inhibiting the angiogenesis of a target blood vessel, comprising:

bringing a compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof into contact with the vascular endothelial cells of a target blood vessel.