4-arylamino-quinazolines and analogs as activators of caspases and inducers of apoptosis and the use thereof

1. A compound according to Formula VIb:

or pharmaceutically acceptable salts thereof, wherein:

R 1 is methyl or ethyl;

R 5 is H or F;

R 2 is halo, N 3 , NH 2 , C 1-6 alkyl, -thio-C 1-6 alkyl, C 2-8 alkynyl, C 1-6 alkoxy, halo-C 1-6 alkyl, hydroxy-C 1-6 alkyl, —C(O)O—C 1-6 alkyl, —N(R a )(R b ), N(R a )(R b )—C 1-6 alkyl-, wherein R a and R b are independently H, OH (R a and R b are not both OH), C 2-6 hydroxyalkyl, or C 1-6 alkyl, or R a and R b together with the nitrogen atom to which they are both linked form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl, wherein when R a and/or R b are C 1-6 alkyl, then R a and R b are independently optionally substituted with C 2-8 alkenyl or —N(R aa )(R bb ), wherein R aa and R bb are independently H, C 1-6 alkyl or R aa and R bb together with the nitrogen atom to which they are both linked form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl;

R 3 , is H, halo, C 1-6 alkyl, or C 1-6 alkoxy;

R 4 , is H, halo, C 1-6 alkyl, or C 1-6 alkoxy, N 3 , nitro, or —N(R a )(R b ), wherein R a and R b are independently H or C 1-6 alkyl;

R 6 , is H, halo, or C 1-6 alkyl;

R 7 , R 8 , R 10 , and R 11 are H, halo, or C 1-6 alkoxy;

and

R 9 is H, halo, N 3 , OH, nitro, NH 2 , C 1-6 alkyl, C 1-6 alkoxy optionally substituted with 1-3 halo substituents, thio-C 1-6 alkyl, —C(O)O—C 1-6 alkyl, —N(R a )(R b ), wherein R a and R b are independently H or C 1-6 alkyl wherein optionally R 9 and R 10 together form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl;

provided that when R 9 is H then R 8 and R 10 are not both H or one H and the other halo.

2. The compound of claim 1 , wherein when R 9 is H then at least one of R 8 and R 10 is not H or halo.

3. The compound of claim 1 , wherein: R 1 is methyl or ethyl; R 2 it is methyl, ethyl, Cl, F, fluoromethyl, C 1-3 hydroxyalkyl, NH 2 , NH 2 OH, NHCH 2 CH 2 OH, NHCH 3 , N(CH 3 ) 2 , N 3 , morpholino, OCH 3 , OC 2 H 5 , or SCH 3 ; R 3 is H, CH 3 , OCH 3 , F, or Cl; R 4 is H, CH 3 , NH 2 , N 3 , F, or Cl; R 5 is H; R 6 is H, CH 3 , F, or Cl; R 7 and R 11 are independently H, F, or OCH 3 ; R 8 and R 10 are independently H, F, Cl, or OCH 3 ; and R 9 is selected from the group consisting of H, OH, N 3 , Cl, C 1-3 alkyl, or —OR 9a where R 9a is C 1-3 alkyl or C 1-3 haloalkyl, —N(R 2b )(R 2c ) wherein R 2b and R 2c are independently C 1-3 alkyl, or —COOR 9b where R 9b is C 1-3 alkyl, and optionally R 10 and R 9 together form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl; provided that when R 9 is H, at least one of R 8 and R 10 is OCH 3 , and when R 9 is C 1-3 alkyl or C 1-3 haloalkyl or Cl, R 2 is Cl or methyl or ethyl.

4. The compound of claim 1 , wherein R 9 is H; OH; Cl; N 3 ; C 1-3 alkyl; —OR 9a where R 9a is C 1-4 alkyl or C 1-3 haloalkyl; —NH(R a ) or —N(R a )(R b ) where R a and R b are independently C 1-3 alkyl; or —COOR 9b where R 9b is C 1-3 alkyl; and optionally R 9 and R 10 together form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl.

5. The compound of claim 1 , wherein R 2 is halo; N 3 ; C 1-6 alkyl optionally substituted with OH or halo; —XR 2a wherein X is S or O, and R 2a is C 1-6 alkyl; —CO 2 R d wherein R d is C 1-3 alkyl; or —N(R a )(R b ) wherein R a and R b are independently H, OH (R a and R b are not both OH), C 1-6 alkyl, C 1-6 hydroxyalkyl, or C 1-6 alkyl that is optionally substituted with —N(R e )(R f ) wherein R e and R f are independently H, or C 1-3 alkyl, and wherein optionally R a and R b together with the nitrogen atom to which they are both linked may form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl.

6. The compound of claim 1 , wherein R 2 is halo; C 1-3 alkyl optionally substituted with OH or halo; —XR 2a wherein X is S or O and R 2a is C 1-3 alkyl; or —N(R a )(R b ) wherein R a and R b are independently H, OH (R a and R b are not both OH), C 1-3 alkyl, C 2-3 hydroxyalkyl.

7. The compound of claim 1 , wherein R 2 is methyl, ethyl, Cl, F, fluoromethyl, C 1-3 hydroxyalkyl, NH 2 , NHOH, —NHCH 2 CH 2 OH, NHCH 3 , N(CH 3 ) 2 , N 3 , morpholino, OCH 3 , OC 2 H 5 or SCH 3 .

8. The compound of claim 1 , wherein R 2 is methyl, Cl, —CH 2 OH, —NH 2 , —NHCH 3 , —NHCH 2 CH 2 OH, —OCH 3 , —SCH 3 , or —CH 2 F.

9. The compound of claim 1 , wherein when R 9 is H, then R 8 or R 10 or both are C 1-3 alkoxy.

10. The compound of claim 1 , wherein when R 9 is C 1-6 alkyl or C 1-6 haloalkyl, then R 2 is methyl, ethyl, Cl, F, fluoromethyl, C 1-3 hydroxyalkyl, NH 2 , NHOH, —NHCH 2 CH 2 OH, NHCH 3 , N(CH 3 ) 2 , N 3 , morpholino, OCH 3 , OC 2 H 5 , or SCH 3 .

11. The compound of claim 1 , wherein R 9 is N 3 ; —OR 9a , wherein R 9a is C 1-3 alkyl optionally substituted with 1-3 F; —N(R a )(R b ) where R a and R b are independently C 1-3 alkyl; or —COOR 9b where R 9b is C 1-3 alkyl.

12. The compound of claim 1 , wherein R 9 is —OCH 3 , —OC 2 H 5 , —N(CH 3 ) 2 , —CO 2 CH 3 , —OCHF 2 , or N 3 .

13. The compound of claim 1 , wherein R 1 is CH 3 ; R 2 is methyl, ethyl, Cl, F, fluoromethyl, CH 2 OH, NH 2 , NHCH 3 , N(CH 3 ) 2 , —NHCH 2 CH 2 OH, OCH 3 , or SCH 3 ; R 3 is H, CH 3 , OCH 3 , F, or Cl; R 4 is H, CH 3 , NH 2 , F, or Cl; R 5 is H; R 6 is H, F or Cl; R 7 and R 11 are independently H, F, or OCH 3 ; R 8 and R 10 are independently H, F, Cl, or OCH 3 ; and R 9 is selected from the group consisting of —OR 12 where R 12 is methyl, ethyl, fluoromethyl or fluoroethyl, —NHCH 3 , N(CH 3 ) 2 , N 3 , and —COOR 13 where R 13 is methyl or ethyl.

14. The compound of claim 1 , wherein R 1 is CH 3 ; R 2 is methyl, Cl, —CH 2 OH, —NH 2 , —NHCH 3 , —NHCH 2 CH 2 OH, —OCH 3 , —SCH 3 , or —CH 2 F; R 3 is H, —CH 3 , OCH 3 , or Cl; R 4 is H, CH 3 , or NH 2 ; R 5 is H; R 6 is H, or CH 3 ; R 7 and R 11 are independently H, or F; R 8 and R 10 are independently H, or F or OCH 3 ; and R 9 is —OCH 3 or —OC 2 H 5 , —N(CH 3 ) 2 , —CO 2 CH 3 , —OCHF 2 , or N 3 .

15. The compound of claim 1 , wherein R 1 is CH 3 ; R 2 is Cl, methyl or CH 2 F; R 3 is H, CH 3 , F or Cl; R 4 , R 5 and R 6 are H; R 7 , R 8 , R 10 and R 11 are independently H or F; and R 9 is —OCH 3 or —N(CH 3 ) 2 .

16. A compound selected from the group consisting of:

N 2 -Hydroxyl-N 4 -(4-methoxy-phenyl)-N 4 -methyl-quinazoline-2,4-diamine;

N 2 -(2-Hydroxylethyl)-N 4 -(4-methoxy-phenyl)-N 4 -methyl-quinazoline-2,4-diamine;

4-(4-methoxy-phenyl)-N 4 -methyl-quinazoline-2,4-diamine;

N 2 -(3,7-Dimethyl-octa-2,6-dienyl)-N 4 -(4-methoxy-phenyl)-N 4 -methyl-quinazoline-2,4-diamine;

4-(4-Methoxy-phenyl)-N 4 -methyl-N 2 -(2-morpholin-4-yl-ethyl)-quinazoline-2,4-diamine;

(4-Methoxy-phenyl)-methyl-(2-morpholin-4-yl-quinazolin-4-yl)-amine;

N 2 -[2-(1H-Imidazol-4-yl)-ethyl]-N 4 -(4-methoxy-phenyl)-N 4 -methyl-quinazoline-2,4-diamine;

N 2 -(3-Dimethylamino-propyl)-N 4 -(4-methoxy-phenyl)-N 4 -methyl-quinazoline-2,4-diamine;

5-Chloro-N 2 ,N 4 -bis-(4-methoxy-phenyl)-N 2 ,N 4 -dimethyl-quinazoline-2,4-diamine;

6-Chloro-N 2 ,N 4 -bis-(4-methoxy-phenyl)-N 2 ,N 4 -dimethyl-quinazoline-2,4-diamine;

(2-Dimethylamino-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine; and

(2-Methylamino-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

or a pharmaceutically acceptable salt thereof.

17. A compound selected from the group consisting of:

(2-Fluoromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(4-Methoxy-phenyl)-methyl-(2-methyl-quinazolin-4-yl)-amine;

(2-Chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(2-Ethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

Ethyl 4-(N-(4-methoxy-phenyl)-N-methylamino)quinazoline-2-carboxylate;

(2-hydroxymethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(2-Dimethylaminomethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(4-Difluoromethoxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(3-Fluoro-4-methoxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Isopropoxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Ethyl-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(5-Methoxy-2-methyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(4-Hydroxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(2-Fluoro-4-methoxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(2-Methyl-quinazolin-4-yl)-(4-nitro-phenyl)-methyl-amine;

(4-Amino-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Azido-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Amino-2,6-dibromo-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Amino-2-bromo-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Dimethylamino-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Ethoxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Methoxy-phenyl-2,3,5,6-d 4 )-(2-methyl-quinazolin-4-yl)-methyl-amine;

(4-Methoxy-phenyl)-(2-methyl-6-nitro-quinazolin-4-yl)-methyl-amine;

(6-Amino-2-methyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(6-Azido-2-methyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(2,4,6-Trimethoxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine; and

(4-Fluoro-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

or a pharmaceutically acceptable salt thereof.

18. A compound selected from the group consisting of:

(2-Chloro-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(4-methyl-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(4-chloro-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(4-nitro-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(4-trifluoromethoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(2,3-dimethoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-ethyl-(4-methoxy-phenyl)-amine;

(2-Chloro-quinazolin-4-yl)-(2,4-dimethoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(2,5-dimethoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(3-methoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(2-methoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(4-methylcarboxyphenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(4-hydroxyphenyl)-methylamine;

(2-Chloro-6-methyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(2-Chloro-5-methyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(2-Chloro-8-methyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(2,6-Dichloro-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(3,4-methylenedioxyphenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(3,4-dimethoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(4-propoxy-phenyl)-methyl-amine;

(2-Chloro-quinazolin-4-yl)-(4-ethoxy-phenyl)-methyl-amine;

(2,8-Dichloro-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine; and

(2,5-Dichloro-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine;

or a pharmaceutically acceptable salt thereof.

19. The compound (2-methoxy-quinazolin-4-yl)-(4-methoxyphenyl)-methylamine, or a pharmaceutically acceptable salt thereof.

20. The compound (2-methylthio-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine, or a pharmaceutically acceptable salt thereof.

21. The compound (2-azido-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine, or a pharmaceutically acceptable salt thereof.

22. The compound (4-methoxy-phenyl)-methyl-(2-methyl-quinazolin-4-yl)-amine hydrochloride.

23. The compound (4-Dimethylamino-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine, or a pharmaceutically acceptable salt thereof.

24. A compound according to Formula VIb:

or pharmaceutically acceptable salts thereof, wherein:

R 1 is methyl or ethyl;

R 5 is H or F;

R 2 is H, halo, N 3 , NH 2 , C 1-6 alkyl, C 2-8 alkynyl, C 1-6 alkoxy, halo-C 1-6 alkyl, hydroxy-C 1-6 alkyl, —C(O)O—C 1-6 alkyl, N(R a )(R b )—C 1-6 alkyl-, wherein R a and R b are independently H, OH (R a and R b are not both OH), C 2-6 hydroxyalkyl, or C 1-6 alkyl, or R a and R b together with the nitrogen atom to which they are both linked form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl, wherein when R a and/or R b are C 1-6 alkyl, then R a and R b are independently optionally substituted with C 2-8 alkenyl or —N(R aa )(R bb ), wherein R aa and R bb are independently H, C 1-6 alkyl or R aa and R bb together with the nitrogen atom to which they are both linked form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl;

R 3 , is H, halo, C 1-6 alkyl, or C 1-6 alkoxy;

R 4 , is H, halo, C 1-6 alkyl, or C 1-6 alkoxy, N 3 , nitro, or —N(R a )(R b ), wherein R a and R b are independently H or C 1-6 alkyl;

R 6 , is H, halo, or C 1-6 alkyl;

R 7 , R 8 , R 10 , R 11 are H, halo, or C 1-6 alkoxy; and

provided that R 9 is H; OH; Cl; N 3 ; C 1-3 alkyl; C 1-3 haloalkyl; —OR 9a where R 9a is C 1-4 alkyl or C 1-3 haloalkyl; —NH(R a ) or —N(R a )(R b ) where R a and R b are independently C 1-3 alkyl; or —COOR 9b where R 9b is C 1-3 alkyl; and optionally R 9 and R 10 together form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl; and

provided that when R 9 is H then R 8 and R 10 are not both H or one H and the other halo.

25. The compound of claim 24 , wherein when R 9 is H then at least one of R 8 and R 10 is not H or halo.

26. The compound of claim 24 , wherein R 1 is methyl or ethyl; R 2 is H, methyl, ethyl, Cl, F, fluoromethyl, C 1-3 hydroxyalkyl, NH 2 , NH 2 OH, NHCH 2 CH 2 OH, NHCH 3 , N(CH 3 ) 2 , N 3 , morpholino, OCH 3 , OC 2 H 5 , or SCH 3 ; R 3 is H, CH 3 , OCH 3 , F, or Cl; R 4 is H, CH 3 , NH 2 , N 3 , F, or Cl; R 5 is H; R 6 is H, CH 3 , F, or Cl; R 7 and R 11 are independently H, F, or OCH 3 ; R 8 and R 10 are independently H, F, Cl, or OCH 3 ; and R 9 is selected from the group consisting of H, OH, N 3 , Cl, C 1-3 alkyl, C 1-3 haloalkyl, or —OR 9a where R 9a is C 1-3 alkyl or C 1-3 haloalkyl, —N(R 2b )(R 2c ) wherein R 2b and R 2c are independently C 1-3 alkyl, or —COOR 9b where R 9b is C 1-3 alkyl, and optionally R 10 and R 9 together form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl; provided that when R 9 is H, at least one of R 8 and R 10 is OCH 3 , and when R 9 is C 1-3 alkyl or Cl, R 2 is Cl or methyl or ethyl.

27. The compound of claim 24 , wherein R 2 is H; halo; N 3 ; C 1-6 alkyl optionally substituted with OH or halo; —XR 2a wherein X is S or O, and R 2a is C 1-6 alkyl; —CO 2 R d wherein R d is C 1-3 alkyl; or —N(R a )(R b ) wherein R a and R b are independently H, OH (R a and R b are not both OH), C 1-6 alkyl, C 1-6 hydroxyalkyl, or C 1-6 alkyl that is optionally substituted with —N(R e )(R f ) wherein R e and R f are independently H or C 1-3 alkyl, and wherein optionally R a and R b together with the nitrogen atom to which they are both linked may form a 5 or 6-membered heterocycle selected from the group consisting of: tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, morpholinyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl.

28. The compound of claim 24 , wherein R 2 is H; halo; C 1-3 alkyl optionally substituted with OH or halo; —XR 2a wherein X is S or O and R 2a is C 1-3 alkyl; or —N(R a )(R b ) wherein R a and R b are independently H, OH (R a and R b are not both OH), C 1-3 alkyl, C 2-3 hydroxyalkyl.

29. The compound of claim 24 , wherein R 2 is H, methyl, ethyl, Cl, F, fluoromethyl, C 1-3 hydroxyalkyl, NH 2 , NHOH, —NHCH 2 CH 2 OH, NHCH 3 , N(CH 3 ) 2 , N 3 , morpholino, OCH 3 , OC 2 H 5 or SCH 3 .

30. The compound of claim 24 , wherein R 2 is H, methyl, Cl, —CH 2 OH, —NH 2 , —NHCH 3 , —NHCH 2 CH 2 OH, —OCH 3 , —SCH 3 , or —CH 2 F.

31. The compound of claim 24 , wherein when R 9 is H, then R 8 or R 10 or both are C 1-3 alkoxy.

32. The compound of claim 24 , wherein R 9 is N 3 ; —OR 9a , wherein R 9a is C 1-3 alkyl optionally substituted with 1-3 F; —N(R a )(R b ) where R a and R b are independently C 1-3 alkyl; or —COOR 9b where R 9b is C 1-3 alkyl.

33. The compound of claim 24 , wherein R 9 is —OCH 3 , —OC 2 H 5 , —N(CH 3 ) 2 , —CO 2 CH 3 , —OCHF 2 , or N 3 .

34. The compound of claim 24 , wherein R 1 is CH 3 ; R 2 is H, methyl, ethyl, Cl, F, fluoromethyl, CH 2 OH, NH 2 , NHCH 3 , N(CH 3 ) 2 , —NHCH 2 CH 2 OH, OCH 3 , or SCH 3 ; R 3 is H, CH 3 , OCH 3 , F, or Cl; R 4 is H, CH 3 , NH 2 , F, or Cl; R 5 is H; R 6 is H, CH 3 , F, or Cl; R 7 and R 11 are independently H, F, or OCH 3 ; R 8 and R 10 are independently H, F, Cl, or OCH 3 ; and R 9 is selected from the group consisting of —OR 12 where R 12 is methyl, ethyl, fluoromethyl or fluoroethyl, —NHCH 3 , N(CH 3 ) 2 , N 3 , and —COOR 13 where R 13 is methyl or ethyl.

35. The compound of claim 24 , wherein R 1 is CH 3 ; R 2 is H, methyl, Cl, —CH 2 OH, —NH 2 , —NHCH 3 , —NHCH 2 CH 2 OH, —OCH 3 , —SCH 3 , or —CH 2 F; R 3 is H, —CH 3 , OCH 3 , or Cl; R 4 is H, CH 3 , or NH 2 ; R 5 is H; R 6 is H, or CH 3 ; R 7 and R 11 are independently H, or F; R 8 and R 10 are independently H, or F or OCH 3 ; and R 9 is —OCH 3 or —OC 2 H 5 , —N(CH 3 ) 2 , —CO 2 CH 3 , —OCHF 2 , or N 3 .

36. The compound of claim 24 , wherein R 1 is CH 3 ; R 2 is Cl, methyl or CH 2 F; R 3 is H, CH 3 , F or Cl; R 4 , R 5 and R 6 are H; R 7 , R 8 , R 10 and R 11 are independently H or F; and R 9 is —OCH 3 or —N(CH 3 ) 2 .

37. A compound selected from the group consisting of:

(4-Methoxy-phenyl)-methyl-quinazolin-4-yl-amine; and

(4-Methyl-phenyl)-methyl-quinazolin-4-yl-amine;

or a pharmaceutically acceptable salt thereof.

38. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound according to claim 1 .

39. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound according to claim 24 .

40. The compound (4-methoxy-phenyl)-methyl-(2-methyl-quinazolin-4-yl)-amine, or a pharmaceutically acceptable salt thereof.

41. A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to claim 1 .

42. A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to claim 16 .

43. A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to claim 17 .

44. A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to claim 18 .

45. A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to claim 22 .

46. A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to claim 24 .

47. A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to claim 37 .

48. A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to claim 40 .