Substituted quinazoline compounds and their use in treating angiogenesis-related diseases

1. A compound of the following formula:

in which

each of R 1 , R 2 , R 3 , R 4 , R 5 , R 8 , R 9 , and R 10 , independently, is H, halo, amino, hydroxy, alkyl, alkenyl, alkynyl, heterocycloalkyl, alkoxy, alkylthio,-carboxy, alkoxycarbonyl, carbonylamino, or sulfonylamino, or R 3 and R 4 , together with the carbon atoms to which they are attached, form a 4- to 7-membered saturated, unsaturated, or aromatic ring, optionally containing 1-3 hetero atoms selected from N, O and S;

R 6 is alkyl;

R 7 is alkoxycarbonyl, aminocarbonyl, or aminosulfonyl;

X is O; and

Z is N;

wherein each of alkyl, alkenyl, alkynyl, heterocycloalkyl, and alkoxy is optionally substituted with at least one substituent chosen from halo, hydroxyl, amino, cyano, nitro, mercapto, alkoxycarbonyl, amido, carboxy, alkanesulfonyl, alkylcarbonyl, carbamido, carbamoyl, carboxyl, thioureido, thiocyanato, sulfonamido, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl.

2. A compound of the following formula:

wherein

each of R 1 , R 2 , R 3 , R 4 , R 5 , R 8 , R 9 , and R 10 , independently, is H, halo, amino, hydroxy, alkyl, alkenyl, alkynyl, heterocycloalkyl, alkoxy, alkylthio,-carboxy, alkoxycarbonyl, carbonylamino, or sulfonylamino, or R 3 and R 4 , together with the carbon atoms to which they are attached, form a 4- to 7-membered saturated, unsaturated, or aromatic ring, optionally containing 1-3 hetero atoms selected from N, O and S;

R 6 is alkyl;

R 7 is —C(O)NR a R b , each of R a and R b , independently, being H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, or R a and R b , together with the nitrogen atom to which they are attached, represent a 3-8 membered ring containing 1-3 heteroatoms;

X is O; and

Z is N;

wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and alkoxy is optionally substituted with at least one substituent chosen from halo, hydroxyl, amino, cyano, nitro, mercapto, alkoxycarbonyl, amido, carboxy, alkanesulfonyl, alkylcarbonyl, carbamido, carbamoyl, carboxyl, thioureido, thiocyanato, sulfonamido, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl.

3. The compound of claim 1 , wherein R 6 is optionally substituted methyl.

4. The compound of claim 3 , wherein R 6 is methyl.

5. The compound of claim 1 , wherein each of R 3 and R 4 is optionally substituted alkoxy.

6. The compound of claim 2 , wherein each of R 3 and R 4 is optionally substituted alkoxy.

7. The compound of claim 2 , wherein each of R a and R b , independently, is H, optionally substituted alkyl, or optionally substituted cycloalkyl.

8. The compound of claim 7 , wherein R a is H and R b is optionally substituted methyl.

9. The compound of claim 7 , wherein each of R 3 and R 4 is methoxy.

10. A compound of the formula:

11. A pharmaceutical composition comprising a compound of the following formula:

wherein

each of R 1 , R 2 , R 3 , R 4 , R 5 , R 8 , R 9 , and R 10 , independently, is H, halo, amino, hydroxy, alkyl, alkenyl, alkynyl, heterocycloalkyl, alkoxy, alkylthio,-carboxy, alkoxycarbonyl, carbonylamino, or sulfonylamino, or R 3 and R 4 , together with the carbon atoms to which they are attached, form a 4- to 7-membered saturated, unsaturated, or aromatic ring, optionally containing 1-3 hetero atoms selected from N, O and S;

R 6 is alkyl;

R 7 is alkoxycarbonyl, aminocarbonyl, or aminosulfonyl;

X is O; and

Z is N;

wherein each of alkyl, alkenyl, alkynyl, heterocycloalkyl, and alkoxy is optionally substituted with at least one substituent chosen from halo, hydroxyl, amino, cyano, nitro, mercapto, alkoxycarbonyl, amido, carboxy, alkanesulfonyl, alkylcarbonyl, carbamide, carbamoyl, carboxyl, thioureido, thiocyanato, sulfonamido, alkyl, alkenyl, alkynyl, alkyloxy, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;

and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising a compound of the formula:

and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising a compound of the following formula:

wherein

each of R 1 , R 2 , R 3 , R 4 , R 5 , R 8 , R 9 , and R 10 , independently, is H, halo, amino, hydroxy, alkyl, alkenyl, alkynyl, heterocycloalkyl, alkoxy, alkylthio,-carboxy, alkoxycarbonyl, carbonylamino, or sulfonylamino, or R 3 and R 4 , together with the carbon atoms to which they are attached, form a 4- to 7-membered saturated, unsaturated, or aromatic ring, optionally containing 1-3 hetero atoms selected from N, O and S;

R 6 is alkyl;

R 7 is —C(O)NR a R b , each of R a and R b , independently, being H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, or R a and R b , together with the nitrogen atom to which they are attached, represent a 3-8 membered ring containing 1-3 heteroatoms;

X is O; and

Z is N;

wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with at least one substituent chosen from halo, hydroxyl, amino, cyano, nitro, mercapto, alkoxycarbonyl, amido, carboxy, alkanesulfonyl, alkylcarbonyl, carbamido, carbamoyl, carboxyl, thioureido, thiocyanato, sulfonamido, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;

and a pharmaceutically acceptable carrier.

14. The compound of claim 2 , wherein R 6 is optionally substituted methyl.

15. The compound of claim 14 , wherein R 6 is methyl.

16. The compound of claim 7 , wherein R 6 is optionally substituted methyl.

17. The compound of claim 16 , wherein R 6 is methyl.