Use of substituted quinazoline compounds in treating angiogenesis-related diseases

1. A method of mediating kinase insert domain receptor activity comprising

administering to a subject in need thereof an effective amount of 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;

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, hydroxy, amino, cyano, nitro, mercapto, alkoxycarbonyl, amido, carboxy, alkanesulfonyl, alkylcarbonyl, carbamido, carbamoyl, thioureido, thiocyanato, sulfonamido, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl.

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

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

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

5. The method of claim 1 , wherein R 7 is —C(O)NR a R b , each of R a and R b , independently, being H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, 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;

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

6. The method of claim 5 , wherein each of R a and R b , independently, is H, optionally substituted alkyl, or optionally substituted cycloalkyl.

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

8. The method of claim 6 , wherein R a is H and R b is optionally substituted methyl.

9. The method of claim 6 , wherein each of R 3 and R 4 is methoxy.

10. A method of treating a solid tumor mediated by kinase insert domain receptor activity comprising administering to a subject in need thereof an effective amount of a compound chosen from