IP Library › Granted Patent US 7,678,803

Granted Patent B2

US 7,678,803 · App. 11/844,584 · Granted Mar 16, 2010

Quinazoline derivatives for the treatment of cancer

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Quick Facts

Patent No.: US 7,678,803
App. No.: 11/844,584
Granted: Mar 16, 2010
Kind: B2

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Abstract

The current invention is directed toward compounds and pharmaceutically acceptable salts of Formula I wherein Q 1 is CR 1 , Q 2 is N, Q 4 and Q 5 are each CR 1 , Q 3 is CR 2 , X 1 is N or CRc, Y is CR c , X 2 and X 3 are each C(R 5 )(R 6 ), R 7 is O. Compounds of Formula I are useful in the treatment of diseases and/or conditions related to cell proliferation, such as cancer The current invention is also directed toward pharmaceutical compositions comprising compounds of the invention.

Claims (285)

1. A compound according to the formula I,

or pharmaceutically acceptable salts thereof, wherein

R 0 is hydrogen, halogen, cyano, nitro, or —A—R 0′ ,

wherein

A is a bond, —O—, —S—, —N(R 0′ )—, —N(R 0′ )CO—, —N[C(O)R 0′ ]C(O)—, —N(R 0′ )SO 2 —, —SO 2 N(R 0′ )—, —SO 2 —, —CO—, —CO 2 —, or —C(O)N(R 0′ )—; and

each R 0 is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di—(C 1 -C 6 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl, wherein

the aryl and heteroaryl groups are optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, hydroxy, amino, mono- or di-(C 1 -C 6 ) alkylamino, halo(C 1 -C 6 )alkyl, or carboxamide;

Q 1 , Q 4 , and Q 5 are each CR 1 , wherein

each R 1 is hydrogen, halogen, cyano, nitro, or —B—R 1 ,

wherein

B is a bond, —O—, —S—, —N(R 1′ )—, —N(R 1′ )CO—, —N[C(O)R 1′ ]—C(O)—, —N(R 1′ )SO 2 , —SO 2 N(R 1′ )—, —SO 2 —, —CO—, —CO 2 —, or —C(O)N(R 1′ )—; and

each R 1 is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 —C 6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di-(C 1 -C 6 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl, wherein

the aryl and heteroaryl groups are optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, hydroxy, amino, mono- or di—(C 1 -C 6 ) alkylamino, halo(C 1 -C 6 )alkyl, or carboxamide;

Q 2 is N, Q 3 is CR 2 , wherein

each R 2 is independently

(a)H,

(b) halogen, or

(c) a C 1 -C 15 alkyl group where up to five of the carbon atoms in said alkyl group are optionally replaced independently by R 22, carbonyl, ethenyl, ethynyl or a moiety selected from N, O, S SO 2 or SO, with the proviso that two O atoms, two S atoms, or an O and S atom are not immediately adjacent each other, wherein

R 22 is

(i) heteroaryl,

(ii) aryl,

(iii) saturated or unsaturated C 3 -C 10 cycloalkyl, or

(iv) saturated or unsaturated C 2 -C 10 heterocycloalkyl, wherein each aryl, heteroaryl, saturated or unsaturated cycloalkyl, or saturated or unsaturated heterocycloalkyl, independently, is optionally substituted with at least one group, which independently is hydroxy, halo, amino, cyano, carboxy, carboxamido, nitro, oxo, —S—(C 1 -C 6 )alkyl, —SO 2 —(C 1 - C 6 )alkyl, —SO 2 —aryl, —SO—(C 1 -C 6 )alkyl, —SO—aryl, —SO 2 NH 2 , —SO 2 NH—(C 1 -C 6 )alkyl, —SO 2 NH—aryl, (C 1 -C 6 )alkoxy, or mono- or di—(C 1 -C 10 )alkylamino; and

each R 22 is optionally fused to a C 6 -C 10 aryl group, C 5 —C 8 saturated cyclic group,

or a C 5 —C 10 heterocycloalkyl group;

wherein each (c) is optionally substituted at any available position with C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, hydroxy, carboxy, carboxamido, oxo, halo, amino, cyano, nitro, —SH, —S—(C 1 -C 6 )alkyl, —SO 2 —(C 1 -C 6 )alkyl, —SO 2 NH 2, —SO 2 NH—(C 1 -C 6 )alkyl, —SO 2 NH—aryl, —SO 2 —aryl, —SO—(C 1 -C 6 )alkyl, —SO 2 —aryl, C 1 - C 6 alkoxy, C 2 -C 10 alkenyloxy, C 2 -C 10 alkynyloxy, mono-or di—(C 1 -C 10 )alkylamino, or R 23, wherein

R 23 is

(1) heteroaryl,

(2) aryl,

(3) saturated or unsaturated C 5 -C 10 cycloalkyl, or

(4) saturated or unsaturated C 5 -C 10 heterocycloalkyl, and

the R 23 groups are optionally substituted at least one group which is independently hydroxy, oxo, halo, amino, cyano, nitro, —SH, —S—(C 1 - C 6 )alkyl, —SO 2 —(C 1 -C 6 )alkyl, —SO 2 —aryl, —SO—(C 1 -C 6 )alkyl, —SO—aryl, —SO 2 NH 2, —SO 2 NH—(C 1 -C 6 )alkyl, —SO 2 NH—aryl, (C 1 -C 6 )alkoxy, or mono- or di—(C 1 -C 10 )alkylamino;

R 7 is O—;

X 1 is N or CR c , Y is CR c , wherein

each R c independently is hydrogen, halogen, cyano, nitro, C 1 -C 10 alkyl,C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl(C 1 -C 10 )alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, hydroxy, amino, mono- or di—(C 1 -C 6 ) alkylamino, cyano, nitro, halo (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl, wherein

X 2 and X 3 are independently C(R 5 )(R 6 ), wherein

each R 5 and R 6 is independently hydrogen, C 1 -C 6 alkyl, or mono- or di—(C 1 -C 6 )alkylamino(C 1 -C 6 )alkykl;

n is 1.

2. The compound according to claim 1 , wherein

R 0 is hydrogen, halogen, C 1 -C 3 alkyl, or —A—R 0′ , wherein

A is —O—, —N(R 0′ )—, —N(R 0′ )CO—, —N[C (O)R 0′ ]C(O)—, or—N(R 0′)SO 2 —; and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

3. The compound according to claim 2 , wherein

R 0 is —N(R 0′ ) 2 —, wherein

each R 0 is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 —C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

4. The compound according to claim 3 , wherein

R 0 is —N(R 0′ ) 2 —, wherein

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl.

5. The compound according to claim 1 , wherein

R 1 is hydrogen, or —B—R 1 ,

wherein

B is a bond, —O—, or —N(R 1′ )—, and

each R 1′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

6. The compound according to claim 1 , wherein X 1 is N.

7. The compound according to claim 1 , wherein X 1 is CR c .

8. The compound according to claim 1 , wherein X 1 is N, Y is CR c ,

R c is hydrogen, halogen, C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl(C 1 -C 10 )alkyl.

9. The compound according to claim 1 , wherein X 1 is CR c , Y is CR c , wherein

each R c is independently hydrogen, halogen, C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, or 3 -C 7 cycloalkyl(C 1 -C 10 )alkyl.

10. The compound according to claim 1 , of the formula IA

wherein

R 0 is hydrogen, halogen, C 1 -C 3 alkyl, or —A—R 0′ , wherein

A is — 0 —, —N(R 0′ )—, —N(R 0′ )CO—, —N[C(O)R 0′ ]C(O)—, or—N(R 0′ )SO 2 —; and

each R 0 is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 0 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di—(C 1 —C 6 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl.

11. The compound according to claim 10 , wherein

R 0 is —N(R 0′ ) 2 —, wherein

each R 0 is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

12. The compound according to claim 10 , wherein

Q 1 is CR 1 ,

wherein R 1 is hydrogen, or —B—R 1′ , wherein

B is a bond, —O—, or —N(R 1′ )—, and

each R 1 is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 C 6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di—(C 1 -C 6 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl.

13. The compound according to claim 10 , wherein

Q 3 is CR 2 wherein

each R 2 is independently

(a)H,

(b) halogen, or

wherein each (c) is optionally substituted at any available position with C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, hydroxy, carboxy, carboxamido, oxo, halo, amino, cyano, nitro, —SH, —S—(C 1 - C 6 )alkyl, —SO 2 -(C 1 -C 6 )alkyl, —SO 2 NH 2 , —SO 2 NH—(C 1 -C 6 )alkyl, —SO 2 NH—aryl, —SO 2 —aryl, —SO—(C 1 C 6 )alkyl, —SO 2 —aryl, C 1 -C 10 alkoxy, C 2 C 10 alkenyloxy, C 2 C 10 alkynyloxy, mono(C 1 -C 10 )alkylamino, or di(C 1 -C 10 )alkylamino.

14. The compound according to claim 10 , wherein X 1 is N.

15. The compound according to claim 10 , wherein X 1 is CR c .

16. The compound according to claim 14 , wherein Y is CR c ,

wherein R c is hydrogen, halogen, C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl(C 1 C 10 )alkyl.

17. The compound according to claim 15 , wherein Y is CR c ,

wherein each R c is independently hydrogen, halogen, C 1 C 10 alkyl, C 1 C 10 haloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl(C 1 C 10 )alkyl.

18. The compound according to claim 1 , of the formula IB

wherein

R 0 is hydrogen, halogen, C 1 -C 3 alkyl, or A—R 0′ , wherein

A is —O—, —N(R 0′ )—, —N(R 0′ )CO—, —N[C(O)R 0′ ] C(O)—, or —N(R 0′ )SO 2 —; and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

19. The compound according to claim 18 , wherein

R 0 is —N(R 0′ ) 2 —, and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 —C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

20. The compound according to claim 18 , wherein

R 1 is hydrogen, or —B—R 1′ ,

wherein

B is a bond, —O—, or —N(R 1′ )—, and

each R 1′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di-(C 1 -C 6 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl.

21. The compound according to claim 18 , wherein X 1 is N.

22. The compound according to claim 18 , wherein X 1 is CR c .

23. The compound according to claim 18 , wherein Y is CR c ,

wherein each R c is independently hydrogen, halogen, C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl(C 1 -C 10 )alkyl.

24. The compound according to claim 1 , of the formula IC

wherein

R 0 is hydrogen, halogen, C 1 -C 3 alkyl, or —A—R 0′ , wherein

A is —O—, —N(R 0′ )—, —N(R 0′ )CO—, —N[C(O)R 0′ ] C(O)—, or—N(R 0′ )SO 2 —; and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

25. The compound according to claim 24 , wherein

R 0 is —N(R 0′ ) 2 —, and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di—(C 1 -C 8 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl.

26. The compound according to claim 24 , wherein

R 1 is hydrogen, or —B—R 1′ ,

wherein

B is a bond, —O—, or —N(R 1′ )—, and

each R 1′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 - C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 1 -C 1 -C 6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di—(C 1 -C 6 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl.

27. The compound according to claim 24 , wherein

R c is hydrogen, halogen, C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl(C 1 -C 10 )alkyl.

28. The compound according to claim 1 , of the formula ID

wherein

R 1 is hydrogen, or —B—R 1′ ,

wherein

B is a bond, —O—, or —N(R 1′ )—, and

each R 1′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

29. The compound according to claim 28 , wherein

R c is hydrogen, halogen, C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl(C 1 -C 10 )alkyl.

30. The compound according to claim 1 , of the formula IE

wherein

R 0 is hydrogen, halogen, C 1 -C 3 alkyl, or —A—R 0′ , wherein

A is —O—, —N(R 0′ )—, —N(R 0′ )CO—, —N[0(O)R 0′ ]C(O)—, or —N(R 0′ )SO 2 -; and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 6 alkyl, C 0 -C 6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di—(C 1 C 6 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl.

31. The compound according to claim 30 , wherein

R 0 is —N(R 0′ ) 2 —, and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

32. The compound according to claim 30 , wherein

R 1′ is hydrogen, or —B—R 1′ ,

wherein

B is a bond, —O—, or —N(R 1′ )—, and

each R 1′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

33. The compound according to claim 30 , wherein R c is hydrogen, halogen, C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl(C 1 -C 10 )alkyl.

34. The compound according to claim 1 , of the formula IF

wherein

R 1 is hydrogen, or —B—R 1′ ,

wherein

B is a bond, —O—, or —N(R 1′ )—, and

each R 1 is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

35. The compound according to claim 34 , wherein R c is hydrogen, halogen, C 1 -C 10 alkyl, C 1 -C 10 haloalkyl, C 3 -C 7 cycloalkyl, or C 3 -C 7 cycloalkyl(C 1 -C 10 )alkyl.

36. The compound according to claim 1 , of the formula IG

wherein

R 0 is hydrogen, halogen, C 1 -C 3 alkyl, or —A—R 0′ , wherein

A is —N(R 0′ )—, —N(R 0′ )CO—, —N[C(O)R 0′ ]C(O)—, or —N(R 0′ )SO 2 -; and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

37. The compound according to claim 36 , wherein R 0 is hydroxyl.

38. The compound according to claim 36 , wherein

R 0 is —N(R 0′ ) 2 —, and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, or C 1 -C 10 alkyl.

39. The compound according to claim 38 , wherein R 0 is —NH 2 .

40. The compound according to claim 1 , of the formula IH

wherein

R 0 is hydrogen, halogen, hydroxyl, C 1 -C 3 alkyl or —A—R 0′ , wherein

A is —N(R 0′ )—, —N(R 0′ CO—, —N[C(O)R 0′ ]C(O)—, or —N(R 0′ )SO 2 —; and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, C 1 -C 10 alkyl, or C 3 -C 10 cycloalkyl, C 2 -C 10 heterocycloalkyl, aryl, heteroaryl, wherein

each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C 1 -C 10 alkyl, C 3 -C 10 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di—(C 1 -C 6 ) alkylamino, cyano, nitro, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl.

41. The compound according to claim 40 , wherein R 0 is hydroxyl.

42. The compound according to claim 40 , wherein

R 0 is —N(R 0′ ) 2 —, and

each R 0′ is independently hydrogen, C 1 -C 10 haloalkyl, or C 1 -C 10 alkyl.

43. The compound according to claim 42 , wherein R 0 is —NH 2 .

44. The compound according to claim 1 , selected from the group consisting of

1-(4-Amino-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one;

1-(4-Amino-2-methyl-quinazolin-7-yl)-3,6,6-trimethyl-1 ,5,6,7-tetrahydro-indol-4-one;

1-(2,4-Diamino-q uinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one;

1-(4-Amino-8-fluoro-quinazolin-7-yI)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one;

1-[4-Amino-8-(2-methoxy-ethoxy)-quinazol in-7-yI]-3,6,6-trim ethyl-1,5,6,7-tetrahyd ro-indol-4-one;

1-[4-Amino-8-(2-dimethylamino-ethoxy)-quinazolin-7-yI]-3 ,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one;

1-(4-Amino-quinazolin-7-yI)-3-methyl-1,5,6,7-tetrahydro-indol-4-one;

1-(4-Amino-quinazolin-7-yI)-6,6-dimethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-indazol-4-one;

1-[4-Amino-8-(2-methoxy-ethylamino)-quinazolin-7-yI]-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4- one;

1-(4-Amino-5-fluoro-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one;

1-(4-Amino-5-butylsulfanyl-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one

1-(4-Amino-quinazolin-7-yl)-3-cyclopropylmethyl-3,6,6-dimethyl- 1,5,6,7-tetrahydro-indazol-4-one;

1-(4-Cyclopropylamino-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one;

1-(2-Amino-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one; and

1-(2-Amino-4-methyl-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one;

or pharmaceutically acceptable salts thereof.

45. The compound according to claim 1 , selected from the group consisting of

1-(4-aminoquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-2-methylquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(2,4-diaminoq uinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-fluoroquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-aminoquinazolin-7-yl)-3-methyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-methoxyethoxy)q u inazol in-7-yl)-3,6,6-trimethyl-6, 7-dihydro-1H-indol-4(5H )-one;

1-(4-aminoquinazolin-7-yl)-6,6-dimethyl-3-(trifluoromethyl)-6,7-dihydro-1H-indazol-4(5H)-one;

1-(4-amino-8-(2-(dimethylamino)ethoxy)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1-(4-amino-8-butoxyquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(butylthio)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(butylamino)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-methoxyethylamino)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-hydroxyethoxy)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(3-hydroxypropoxy)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-(dimethylamino)ethylamino)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro- 1H-indol-4(5H )-one;

1-(4-amino-8-(3-methoxypropoxy)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-methoxyquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-ethoxyquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-5-fluoroquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one; 1-(4-amino-8-mercaptoquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-fluoroquinazolin-7-yI)-3,6-dimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(8-(allylthio)-4-aminoquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one; 1-(4-amino-8-hydroxyquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(prop-2-ynyloxy)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(but-3-ynyloxy)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-5-(prop-2-ynyloxy)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(butylthio)quinazolin-7-yI)-3,6-dimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-5-(butylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-aminoethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-(dimethylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1-(4-amino-5-methoxyquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

tert-butyl 2-(4-amino-7-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-1-yI)quinazolin-8-ylthio)ethylcarbamate;

1-(4-amino-5-(3,5-dimethoxybenzyloxy)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1-(4-amino-5-hydroxyquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-chloroquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-(neopentylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1 -(4-aminoquinazolin-7-yI)-3-ethyl-6,6-dimethyl-6,7-dihydro-1H-indazol-4(5H)-one;

1 -(4-aminoquinazolin-7-yI)-3-(cyclopropylmethyl)-6,6-dimethyl-6,7-dihydro-1H-indazol-4(5H)-one;

1-(4-amino-5-fluoroquinazolin-7-yI)-3-ethyl-6,6-dimethyl-6,7-dihydro-1H-indazol-4(5H)-one;

1-(4-aminoquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indazol-4(5H)-one;

1-(4-aminoquinazolin-7-yI)-3-isobutyl-6,6-dimethyl-6,7-dihydro-1H-indazol-4(5H)-one;

1-(4-aminoquinazolin-7-yI)-3-methyl-6,7-dihydro-1H-indazol-4(5H)-one;

1-(4-(cyclopropylamino)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-hydroxyquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-aminoquinazolin-7-yI)-2,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-aminoquinazolin-7-yI)-2,3,6,6-tetramethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-hydroxyethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-fluoroquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indazol-4(5H)-one;

2-(4-amino-7-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-1-yI)quinazolin-8- ylthio)acetaldehyde;

1-(4-amino-8-(butylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indazol-4(5H)-one;

1-(2-aminoquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-(isobutylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1-(4-amino-8-(2-(tert-butylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1-(4-amino-8-(2-(isopropylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one; 1-(4-amino-8-(2-(cyclopropylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1-(4-amino-8-(2-(cyclopropylmethylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(2-(methylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1 H-indol-4(5H )-one;

1-(4-amino-8-(2-(ethylamino)ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1 H-indol-4(5H)-one;

1-(4-amino-8-(pyridin-2-ylmethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indazol-4(5H )-one;

1-(4-amino-8-(phenylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(methylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(ethylsulfinyl)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(2,4-diamino-5-fluoroquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(2,4-diamino-5-(ethylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(2-amino-4-methylquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(2-amino-4-methylquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one; 1-(4-amino-8-(2-aminophenylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(isopropylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(dimethylamino)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(cyclopentylthio)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-amino-8-(tetrahydro-2H-pyran-4-yloxy)quinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1-(2-amino-4-ethylquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(2-amino-5-methoxy-4-methylquinazolin-7-yI)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(2-amino-4-methylquinazolin-7-yI)-2,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(2-am ino-4-methylquinazolin-7-yI)-6,7-dihydro-1H-indol-4(5H)-one; 1-(4-amino-8-(3,5-dimethoxybenzyloxy)quinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H )-one;

1-(2-amino-4-chloroquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

1-(4-Amino-quinazolin-7-yl)-3-methyl-1,5,6,7-tetrahydro-indol-4-one;

1-(4-Amino-quinazolin-7-yl)-6,6-dimethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-indazol-4-one; and

1-(2-amino-4-chloroquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one;

or pharmaceutically acceptable salts thereof.

46. A pharmaceutical composition comprising the compound or salt according to claim 1 , and a pharmaceutically acceptable excipient.