Inhibitors of hedgehog pathway

1. A Compound of Formula I

or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof, where

R 1 is alkyl, cycloalkyl, phenyl, or heteroaryl where the cycloalkyl, phenyl, and heteroaryl are optionally substituted with 1, 2, or 3 R 6 ;

R 2 and R 3 together with the pyrimidinyl to which they are attached form a quinazolinyl optionally substituted at the 5-, 6-, 7-, and 8-positions with one or two groups independently selected from alkyl, alkoxy, halo, hydroxy, heterocycloalkylalkyloxy, heterocycloalkyl, and heterocycloalkyl substituted with alkyl; or

R 2 and R 3 together with the pyrimidinyl to which they are attached form a pyrido[3,2-d]pyrimidinyl, pyrido[4,3-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, or pyrido[2,3-d]pyrimidinyl, each of which is optionally substituted at a carbon atom at the 5-, 6-, 7-, and 8-positions with one or two groups independently selected from alkyl, alkoxy, halo, hydroxy, heterocycloalkylalkyloxy, heterocycloalkyl, and heterocycloalkyl substituted with alkyl; or

R 2 and R 3 together with the pyrimidinyl to which they are attached form a 6,7-dihydro-5H-cyclopenta[d]pyrimidinyl, 5,6,7,8-tetrahydroquinazolinyl, or 6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidinyl; or

R 2 and R 3 together with the pyrimidinyl to which they are attached form a 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidinyl, or 5,6,7,8-tetrahydropyrido[2,3-d]pyrimidinyl, each of which is optionally substituted at the 5-, 6-, 7-, and 8-positions with one or two groups independently selected from alkyl, alkoxycarbonyl, benzyloxycarbonyl, and optionally substituted phenylalkyl;

each R 6 , when R 6 is present, is independently selected from alkyl, alkoxy, amino, alkylamino, dialkylamino, halo, haloalkyl, haloalkoxy, halophenyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxyalkyl, alkoxycarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminoalkylamino, alkylaminoalkylamino, dialkylaminoalkylamino, alkyloxyalkylamino, heterocycloalkyl, and heterocycloalkylalkyl; where the heterocycloalkyl, either alone or as part of heterocycloalkylalkyl, is optionally substituted with alkyl or alkoxycarbonyl;

R 40 is hydrogen or alkyl;

R 50 is selected from

n1 is 0, 1, or 2;

each R 5 , when R 5 is present, is independently alkyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, halo, nitro, heterocycloalkyl, heterocycloalkylamino, or heterocycloalkylalkyloxy;

where each heterocycloalkyl, either alone or as part of another group in R 5 , is independently optionally substituted with alkyl or alkoxycarbonyl;

R 4a is hydrogen or alkyl;

R 4 is heteroaryl substituted with one R 8 and additionally substituted with 1 or 2 R 8a , wherein heteroaryl is selected from 1,2,3,4-tetrahydroisoquinolinyl or 2,3,4,5-tetrahydro-1,4-benzoxazepinyl; or R 4 is phenyl substituted with one R 29 and additionally substituted with 1 or 2 R 9a ;

each R 8 is independently alkyl, cycloalkyl, phenylalkyloxyalkyl, or R 9b ;

each R 8a is independently hydrogen, halo, or R 8 ;

each R 9a is independently hydrogen, R 9b , or R 9c ;

R 29 is alkyl substituted with —NR 15 R 15a ; or alkyl substituted with optionally substituted heterocycloalkyl;

each R 9b , when R 9b is present, is independently amino, alkylamino, dialkylamino, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyloxy, aminoalkyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, optionally substituted heteroaryl, cyano, —C(O)R 14 , —CR 14a (═NR 14b ), —C(═NR 24 )R 24a , —S(O) 2 NR 13 R 13a , —NR 23 C(O)R 23a —C(O)NR 12 R 12a , or alkyl substituted with one or two R 11 ;

each R 9c , when R 9c is present, is independently alkyl, haloalkyl, hydroxyalkyl, halo, hydroxy, alkoxy, cyano, nitro, or phenylcarbonyl;

each R 11 is independently selected from hydroxy, —NR 15 R 15a coptionally substituted heteroaryl, optionally substituted heterocycloalkyl, and optionally substituted cycloalkyl;

R 12 is hydrogen or alkyl and R 12a is hydrogen, hydroxy, alkoxy, alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, hydroxyalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, or optionally substituted heteroaryl; or R 12 and R 12a together with the nitrogen to which they are attached form a heterocycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from alkyl, hydroxyalkyl, haloalkyl, alkylcarbonyl, alkoxycarbonyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted phenyl, and optionally substituted phenylalkyl;

R 13 is hydrogen or alkyl;

R 13a is alkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl;

each R 14 is independently hydrogen, alkyl, hydroxy, alkoxy, optionally substituted heteroarylalkyl, or optionally substituted heterocycloalkylalkyl;

each R 14a is hydrogen or alkyl;

R 14b is alkoxy, amino, alkylamino, dialkylamino, or optionally substituted heterocycloalkyl;

R 15 is hydrogen, alkyl, alkoxyalkyl, hydroxyalkyl, or haloalkyl;

R 15a is hydrogen, alkyl, alkoxyalkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, optionally substituted cycloalkyl, or optionally substituted phenylalkyl;

R 23 is hydrogen or alkyl;

R 23a is hydrogen, alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or optionally substituted heterocycloalkylalkyl;

R 24 is hydrogen or alkyl, hydroxy, or alkoxy; and

R 24a is hydroxy, alkoxy, amino, alkylamino, or dialkylamino.

2. The Compound of claim 1 selected from N-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylpyrido[2,3-d]pyrimidin-2-yl)amino]benzamide; and a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

3. The Compound of claim 1 where R 40 is hydrogen and R 2 and R 3 together with the pyrimidinyl to which they are attached form a quinazolinyl optionally substituted at the 5-, 6-, 7- , and 8-positions with one or two groups independently selected from alkyl, alkoxy, halo, and hydroxy; or a single isomer thereof and optionally as a pharmaceutically acceptable salt-thereof.

4. The Compound of claim 3 selected from

4-[(6-chloro-4-phenylquinazolin-2-yl)amino]-N-[2-(pyrrolidin-1-

ylmethyl)phenyl]benzamide;

4-[(6-chloro-4-phenylquinazolin-2-yl)amino]-N-[2-(morpholin-4-

ylmethyl)phenyl]benzamide;

4-[(6-chloro-4-phenylquinazolin-2-yl)amino]-N-{3-

[(dimethylamino)methyl]phenyl}benzamide;

4-[(6-chloro-4-phenylquinazolin-2-yl)amino]-N-{5-

[(dimethylamino)methyl]-2-methylphenyl}benzamide;

4-[(6-chloro-4-phenylquinazolin-2-yl)amino]-N-[2-methyl-5-

(morpholin-4-ylmethyl)phenyl]benzamide;

a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

5. The Compound of claim 3 where R 2 and R 3 together with the pyrimidinyl to which they are attached form a quinazolinyl that is not substituted at the 5-, 6-, 7-, or 8-position; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

6. The Compound of claim 5 where R 1 is alkyl; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

7. The Compound of claim 5 where R 1 is heteroaryl optionally substituted with 1, 2, or 3 R 6 ; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

8. The Compound of claim 5 where R 1 is cycloalkyl optionally substituted with 1, 2, or 3 R 6 ; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

9. The Compound of claim 5 where R 1 is phenyl substituted with one or two R 6 where each R 6 is independently amino, alkylamino, dialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, heterocycloalkylalkyl (optionally substituted with alkyl or alkoxycarbonyl), aminoalkylamino, alkylaminoalkylamino, or dialkylaminoalkylamino; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

10. The Compound of claim 5 where R 1 is unsubstituted phenyl; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

11. The Compound of claim 3 where R 50 is

or a single isomer thereof and optionally as a pharmaceutically acceptable salt-thereof.

12. The Compound of claim 11 where R 4 is heteroaryl substituted with one R 8 , wherein heteroaryl is selected from 1,2,3,4-tetrahydroisoquinolinyl or 2,3,4,5-tetrahydro-1,4-benzoxazepinyl; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

13. The Compound of claim 12 selected from

N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(2,6-dimethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(4-methyl-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[2-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinolin-5-yl]-4-

[(4-phenylquinazolin-2-yl)amino]benzamide;

N-(2-{2-[(phenylmethyl)oxy]ethyl}-1,2,3,4-tetrahydroisoquinolin-

5-yl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide;

4-[(4-phenylquinazolin-2-yl)amino]-N-(2,3,3-trimethyl-1,2,3,4-

tetrahydroisoquinolin-7-yl)benzamide; and

a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

14. The Compound of claim 11 where R 4 is phenyl substituted with R 29 and additionally substituted with 1 or 2 R 9a ; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

15. The Compound of claim 14 where each R 9a is independently hydrogen or alkyl; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

16. The Compound of claim 5 where R 1 is alkyl, cycloalkyl, or heteroaryl, where the cycloalkyl and heteroaryl are optionally substituted with 1, 2, or 3 R 6 ; R 50 is

R 4 is phenyl substituted with one R 29 and additionally substituted with 1 or 2 R 9a and each R 9a is independently hydrogen or R 9c ; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

17. The Compound of claim 1 according to Formula Ic

or a single isomer thereof and optionally as a pharmaceutically acceptable salt-thereof.

18. The Compound of claim 17 selected from N-[2-(hydroxymethyl)-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide; and a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

19. The Compound of claim 17 where R 1 is alkyl or heteroaryl substituted with one R 6 ; and each R 9a is independently hydrogen or R 9c , where R 9c is alkyl; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

20. The Compound of claim 17 where R 1 is phenyl substituted with one or two R 6 where each R 6 , is independently alkylaminoalkyl, dialkylaminoalkyl, amino, alkylamino, dialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, heterocycloalkylalkyl (optionally substituted with alkyl or alkoxycarbonyl), aminoalkylamino, alkylaminoalkylamino, or dialkylaminoalkylamino; and R 9a is hydrogen or R 9c , where R 9c is alkyl; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

21. The Compound of claim 17 where R 1 is unsubstituted phenyl; each R 9a is independently hydrogen or alkyl; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

22. The Compound of claim 20 where R 29 is alkyl substituted with —NR 15 R 15a ; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

23. The Compound of claim 21 where R 29 is alkyl substituted with —NR 15 R 15a ; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

24. The Compound of claim 23 selected from N-{3-[(dimethylamino)methyl]phenyl}-4-[(4-phenylquinazolin-2-yl)amino]benzamide; and a single isomer thereof and optionally as a pharmaceutically acceptable salt-thereof.

25. The Compound of claim 1 according to Formula III

or a single isomer thereof and optionally as a pharmaceutically acceptable salt-thereof.

26. The Compound of claim 25 selected from

N-{5-[(dimethylamino)methyl]-2-methylphenyl}-4-{[4-(4-

fluorophenyl)quinazolin-2-yl]amino}benzamide;

N-{5-[(dimethylamino)methyl]-2-methylphenyl}-4-{[4-(2-

fluorophenyl)quinazolin-2-yl]amino}benzamide;

4-{[4-(3-bromophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(4-chlorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(2-chlorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

N-{5-[(dimethylamino)methyl]-2-methylphenyl}-4-{[4-(1-methylethyl)

quinazolin-2-yl]amino}benzamide;

4-{[4-(2,6-difluorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(2,4-difluorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(2-bromophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(2′-bromobiphenyl-2-yl)quinazolin-2-yl]amino}-N-{5-

[(dimethylamino)methyl]-2-methylphenyl}benzamide;

4-{[4-(3-chlorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(3,5-dichlorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(2,3-dichlorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

N-{5-[(dimethylamino)methyl]-2-methylphenyl}-4-{[4-(1-methyl-1H-

pyrrol-2-yl)quinazolin-2-yl]amino}benzamide;

4-{[4-(2,4-dichlorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(3,4-dichlorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(2,5-dichlorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

N-{5-[(dimethylamino)methyl]-2-methylphenyl}-4-{[4-(2-thienyl)

quinazolin-2-yl]amino}benzamide;

N-{5-[(dimethylamino)methyl]-2-methylphenyl}-4-[(4-pyridin-2-

ylquinazolin-2-yl)amino]benzamide;

4-{[4-(3,5-difluorophenyl)quinazolin-2-yl]amino}-N-{5-[(dimethylamino)

methyl]-2-methylphenyl}benzamide;

4-{[4-(4-fluorophenyl)quinazolin-2-yl]amino}-N-[2-methyl-5-

(morpholin-4-ylmethyl)phenyl]benzamide;

N-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-methylquinazolin-2-

yl)amino]benzamide;

4-[(4-ethylquinazolin-2-yl)amino]-N-[2-methyl-5-(morpholin-4-

ylmethyl)phenyl]benzamide;

4-[(4-cyclopropylquinazolin-2-yl)amino]-N-[2-methyl-5-(morpholin-4-

ylmethyl)phenyl]benzamide;

4-{[4-(1-methylethyl)quinazolin-2-yl]amino}-N-(2-methyl-5-(morpholin-4-

ylmethyl(phenylm]benzamide;

4-{[4-(1-methylethyl)quinazolin-2-]amino}-N-(2-methyl-5-

{[methyl(phenylmethyl)amino]methyl}phenyl)benzamide;

N-(2-methyl-5-{[methyl(phenylmethyl)amino]methyl}phenyl)-4-[(4-

methylquinazolin-2-yl)amino]benzamide;

4-[(4-ethylquinazolin-2-yl)amino]-N-(2-methyl-5-

{[methyl(phenylmethyl)amino]methyl}phenyl)benzamide;

N-[5-(aminomethyl)-2-methylphenyl]-4-{[4-(4-chlorophenyl)quinazolin-2-

yl]amino}benzamide;

2-chloro-N-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

2-fluoro-N-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

3-fluoro-N-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

27. The Compound of claim 25 where R 1 is unsubstituted phenyl; n1 is 0; or a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

28. The Compound of claim 27 selected from

N-{5-[(dimethylamino)methyl]-2-methylphenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-{2-methyl-5-[(4-methylpiperazin-1-yl)methyl]phenyl}-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[2-methyl-5-(pyrrolidin-1-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-{3-[(dimethylamino)methyl]-2-methylphenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-{5-[(diethylamino)methyl]-2-methylphenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-[2-methyl-5-(piperidin-1-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(5-{[cyclohexyl(methyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-{5-[(2,6-dimethylpiperidin-1-yl)methyl]-2-methylphenyl}-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-{2-methyl-5-[(2,2,6,6-tetramethylpiperidin-1-yl)methyl]phenyl}-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[(1,1-dimethylethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[5-(azepan-1-ylmethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(2-methyl-5-{[(1,1,3,3-tetramethylbutyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2-methyl-5-{[(phenylmethyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[5-(3,4-dihydroisoquinolin-2(1H)-ylmethyl)-2-methylphenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2-methyl-5-{[methyl(phenylmethyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2-methyl-5-{[(1-methylethyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[bis(1-methylethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[ethyl(methyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[ethyl(1-methylethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-{5-[1-(dimethylamino)ethyl]-2-methylphenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-[2-methyl-5-(1-morpholin-4-ylethyl)phenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(2-methyl-5-{[(2-methylpropyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2-methyl-5-{[(1-phenylethyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[(1,2-dimethylpropyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{1-[ethyl(3,3,3-trifluoropropyl)amino]ethyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{1-[bis(3,3,3-trifluoropropyl)amino]ethyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2-methyl-5-{[methyl(1-methylethyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[5-(3,4-dihydroquinolin-1(2H)-ylmethyl)-2-methylphenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2-methyl-5-{[(1-methylpropyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-{5-[(cyclopropylamino)methyl]-2-methylphenyl}-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

1-({4-methyl-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)

amino]phenyl}methyl)azetidine-3-carboxylic acid;

N-(5-{[(2-hydroxyethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[(2-hydroxyethyl)(methyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-{5-[(ethylamino)methyl]-2-methylphenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-{2-methyl-5-[(propylamino)methyl]phenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(5-{[(1,3-dimethylbutyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[2-methyl-3-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-[5-({[2-hydroxy-1-(hydroxymethyl)ethyl]amino}methyl)-2-

methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide;

N-[2-methyl-5-({[2-(methyloxy)ethyl]amino}methyl)phenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[(2-hydroxy-1,1-dimethylethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-{5-[(4-acetylpiperazin-1-yl)methyl]-2-methylphenyl}-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[4-(2,2-dimethylpropanoyl)piperazin-1-yl]methyl}-2-

methylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[bis(2-hydroxyethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[5-({bis[2-(methyloxy)ethyl]amino}methyl)-2-methylphenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[4-(cyclopentylcarbonyl)piperazin-1-yl]methyl}-2-methylphenyl)-

4-[(4-phenylquinazolin-2-yl)amino]benzamide;

N-(2-methyl-5-{[4-(phenylcarbonyl)piperazin-1-yl]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[2-methyl-5-({4-[(methyloxy)acetyl]piperazin-1-yl}methyl)phenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[ethyl(2,2,2-trifluoroethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[5-(7-azabicyclo[2.2.1]hept-7-ylmethyl)-2-methylphenyl]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[ethyl(2-hydroxyethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[5-(aminomethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-{4-[(dimethylamino)methyl]-2-methylphenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(4-{[ethyl(1-methylethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2-methyl-4-{[methyl(phenylmethyl)amino]methyl}phenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-{2-methyl-5-[(methylamino)methyl]phenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-{4-[(diethylamino)methyl]-2-methylphenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-[2-methyl-4-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(5-{[4-(cyclopropylcarbonyl)piperazin-1-yl]methyl}-2-methylphenyl)-

4-[(4-phenylquinazolin-2-yl)amino]benzamide;

N-{3-[(diethylamino)methyl]-2-methylphenyl}-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-[3-(azepan-1-ylmethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

N-(4-{[(2-hydroxyethyl)amino]methyl}-2-methylphenyl)-4-

[(4-phenylquinazolin-2-yl)amino]benzamide;

N-(4-{[ethyl(2-hydroxyethyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(5-{[cyclopropyl(methyl)amino]methyl}-2-methylphenyl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-[5-(hydroxymethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)

amino]benzamide;

N-{5-[(cyclopentylamino)methyl]-2-methylphenyl}-4-[(4-

phenylquinazolin-2-yl)amino]benzamide; and

a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

29. A Compound selected from

N-(2-methyl-5-nitrophenyl)-4-[(4-phenylquinazolin-2-

yl)amino]benzamide;

4-[(4-phenylquinazolin-2-yl)amino]-N-(1,2,3,4-tetrahydroisoquinolin-7-

yl)benzamide;

N-(2,6-dimethylphenyl)-4-{[4-(1-methylpiperidin-4-yl)quinazolin-2-

yl]amino}benzamide;

N-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-morpholin-4-

ylquinazolin-2-yl)amino]benzamide;

N-(2,6-dimethylphenyl)-4-[(4-morpholin-4-ylquinazolin-2-

yl)amino]benzamide;

N-(2,6-dimethylphenyl)-4-[(4-phenylpyrido[2,3-d]pyrimidin-2-

yl)amino]benzamide;

N-(2,6-dimethylphenyl)-4-[(4-phenyl-5,6,7,8-tetrahydropyrido[3,4-

d]pyrimidin-2-yl)amino]benzamide;

N-(2,6-dimethylphenyl)-4-{[4-phenyl-7-(phenylmethyl)-5,6,7,8-

tetrahydropyrido[3,4-d]pyrimidin-2-yl]amino}benzamide;

N-(2,6-dimethylphenyl)-4-{[4-phenyl-6-(phenylmethyl)-5,6,7,8-

tetrahydropyrido[4,3-d]pyrimidin-2-yl]amino}benzamide;

N-(2,6-dimethylphenyl)-4-[(4-phenyl-5,6,7,8-tetrahydropyrido[4,3-

d]pyrimidin-2-yl)amino]benzamide;

N-(2,6-dimethylphenyl)-2-(4-methylpiperazin-1-yl)-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2,6-dimethylphenyl)-2-[(1-methylpiperidin-4-yl)amino]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2,6-dimethylphenyl)-2-[(2-morpholin-4-ylethyl)oxy]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2,6-dimethylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]-2-[(2-

pyrrolidin-1-ylethyl)oxy]benzamide;

N-(2,6-dimethylphenyl)-3-[(2-morpholin-4-ylethyl)oxy]-4-[(4-

phenylquinazolin-2-yl)amino]benzamide;

N-(2,6-dimethylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]-3-[(2-

pyrrolidin-1-ylethyl)oxy]benzamide;

N-(2,6-dimethylphenyl)-4-({7-[(3-morpholin-4-ylpropyl)oxy]-4-

phenylquinazolin-2-yl}amino)benzamide; and

a single isomer thereof and optionally as a pharmaceutically acceptable salt thereof.

30. The compound of claim 28 which is N-{2-methyl-5-[(methylamino)methyl]phenyl}-4-[(4-phenylquinazolin-2-yl)amino]benzamide, having the structure

optionally as a pharmaceutically acceptable salt thereof.

31. A pharmaceutical composition comprising a compound according to claim 1 or a single isomer thereof, optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent.

32. A method of preparing a compound of claim 1 which method comprises

reacting an intermediate of formula 8, or a salt, hydrate, solvate, or combination thereof:

where A is CH or N, and D is CH; with an intermediate of formula 9:

to yield a Compound of Formula XI:

and optionally separating individual isomers; and optionally modifying any of the R 6 , R 29 , and R 9a groups; and optionally forming a pharmaceutically acceptable salt thereof; or

reacting an intermediate of formula 11, or a salt, hydrate, solvate, or combination thereof:

where A is CH or N, and D is CH; with an intermediate of formula NHR 12 R 12a to yield a Compound of formula 8f

and optionally separating individual isomers; and optionally modifying any of the R 6 , R 9a , and R 12b groups; and optionally forming a pharmaceutically acceptable salt thereof; or

reacting an intermediate of formula 13, or a salt, hydrate, solvate, or combination thereof:

where A is CH or N, and D is CH; with an intermediate of formula NHR 15 R 15a to yield a Compound of Formula XII:

and optionally separating individual isomers; and optionally modifying any of the R 6 , R 9a , and R 15 groups; and optionally forming a pharmaceutically acceptable salt thereof; or

reacting an intermediate of formula 15a, or a salt, hydrate, solvate, or combination thereof:

where A is CH or N, and D is CH; with an intermediate of formula NH 2 R 15 to yield a Compound of Formula XIII:

and optionally separating individual isomers; and optionally modifying any of the R 6 , R 9a , and R 15 groups; and optionally forming a pharmaceutically acceptable salt thereof; or

reacting an intermediate of formula 23, or a salt, hydrate, solvate, or combination thereof:

where A is CH or N, and D is CH; with an intermediate of formula R 23a C(O)OH or R 23a C(O)Cl to yield a Compound of Formula XIV

and optionally separating individual isomers; and optionally modifying any of the R 6 , R 9a , and R 23a groups; and optionally forming a pharmaceutically acceptable salt thereof; or

reacting an intermediate of formula 26, or a salt, hydrate, solvate, or combination thereof:

where A is CH or N, and D is CH; with an intermediate of formula R″B(OH) 2 where R″ is optionally substituted heteroaryl to yield a Compound of Formula XV:

and optionally separating individual isomers; and optionally modifying any of the R 6 , R 9a , and R″ groups; and optionally forming a pharmaceutically acceptable salt thereof;

reacting an intermediate of formula 31, or a salt, hydrate, solvate, or combination thereof:

where R 1 is cycloalkyl, and D is CH; with an intermediate of formula 9 as defined above to yield a Compound of the Invention of Formula XVI

where R 29 and R 9a are as defined in the Summary of the Invention for a Compound of Formula I; and optionally separating individual isomers; and optionally modifying any of the R 6 , R 1 , R 9a , and R 29 groups; and optionally forming a pharmaceutically acceptable salt thereof; or

reacting an intermediate of formula 33, or a salt, hydrate, solvate, or combination thereof:

where R 1 is phenyl or heteroaryl each of which is optionally substituted with 1, 2, or 3 R 6 and R is alkyl, alkoxycarbonyl, benzyloxycarbonyl, and optionally substituted phenylalkyl with an intermediate of formula 34

where R 29 and R 9a are as defined in the Summary of the Invention for a Compound of Formula I to yield a Compound of the Invention of Formula XVIIa

and optionally separating individual isomers; and optionally modifying any of the R, R 6 , R 1 , R 9a , and R 29 groups; and optionally forming a pharmaceutically acceptable salt thereof.