Pyrimidine derivatives

• US 8,927,547 B2
• Filed: 05/20/2011
• Issued: 01/06/2015
• Est. Priority Date: 05/21/2010
• Status: Active Grant

• Current Assignee: Noviga Research AB
• Original Assignee: Noviga Research AB
• Inventors: Hgberg, Marita, Johansson, Tommy, Dahlstedt, Emma, Smitt, Olof
• Primary Examiner(s): RAO, DEEPAK R
• Application Number:
  US13/697,954
• Publication Number:
  US 20130089518A1
• Time in Patent Office: 1,327 Days
• Field of Search: 544/122, 544/324, 514/235.8, 514/275
• US Class Current: 514/235.8
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

The invention provides novel pyrimidine derivatives of formula I, to methods of preparing such compounds, to pharmaceutical compositions containing such compounds, and to methods for using such compounds in treatment of diseases including cancer; wherein R¹, R², R³, R⁴, R⁵, L, A, D, E, Z, and Y are as defined in the specification.

Claims

1. A compound of formula I or a pharmaceutically acceptable solvate or salt thereof,

2. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein Z and E represent carbon;

and Y, D and A represent nitrogen.

3. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein Z and D represent carbon;

and Y, E and A represent nitrogen.

4. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein Z, A and D represent carbon;

and Y and E represent nitrogen.

5. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein Y and E represent carbon;

and Z, D and A represent nitrogen.

6. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein Y and D represent carbon;

and Z, E and A represent nitrogen.

7. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein Y, A and D represent carbon;

and Z and E represent nitrogen.

8. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein R⁴ represents a heteroaryl that is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, (C₁-C₄)alkyl, (C₁-C₄)alkyl(C₂-C₉) heterocyclyl, (C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl(CO)O(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH₂, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl-OH, (C₁-C₄)alkyl-O(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(C₆-C₁₀)aryl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-O(CO)(C₆-C₁₀)aryl, (C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(C₁-C₄)alkyl, (C₁-C₄)alkyl-N[(C₁-C₄)alkyl][(C₁-C₄)-alkyl], (C₁-C₄)alkyl-NH(CO)(C₁-C₄)alkyl, (C₁-C₄)alkyl-NH(CO)(C₁- C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(CO)(C₆-C₁₀)aryl, (C₁-C₄)alkyl(CN), (C₁-C₄)alkyl(C₆-C₁₀)aryl, (CO)OH, (CO)O(C₁-C₄)alkyl, (CO)NH₂, (CO)NH(C₁-C₄)alkyl, (CO)NH(C₁-C₄)alkyl(CO)OH, (CO)(C₁-C₄)alkyl, (CO)(C₁-C₄)alkyl(C₆-C₁₀)aryl, (CO)(C₁-C₄)alkyl(C₁-C₉)heteroaryl, (CO)(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, (CO)(C₂-C₉)heterocyclyl, (CO)(C₆-C₁₀)aryl, (CO)(C₁-C₉)heteroaryl, (C₆-C₁₀)aryl, (C₆-C₁₀)aryl-halogen, (C₆-C₁₀)aryl-OH, (C₆-C₁₀)aryl-NH₂, (C₆-C₁₀)aryl-O(C₁-C₄)alkyl, (C₁-C₉)heteroaryl, (C₁-C₉)heteroaryl-halogen, (C₁-C₉)heteroaryl-OH, (C₁-C₉)heteroaryl-NH₂, (C₁-C₉)heteroaryl(C₁-C₄)alkyl, (C₁-C₉)heteroaryl-O(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-NH₂, O(C₁-C₄)alkyl, O(C₁-C₄)alkyl(C₆-C₁₀)aryl, O(C₁-C₄)alkyl (C₆-C₁₀)heteroaryl , O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, O(C₁C₄)alkyl (C₂-C₉)heterocyclyl (C₁-C₄) alkyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, O(EtO )_1-3H, O(EtO )_1-3(C₁-C₄)alkyl, O(C₆-C₁₀)aryl, O(CO)(C₁-C₄)alkyl, O(CO)(C₁-C₄)alkyl-NH₂, O(CO)(C₆-C₁₀)aryl, OCF₃, OSO₂(C₁-C₄)alkyl, OSO₂OH, NH(C₁-C₄)alkyl, N[(C₁-C₄)alkyl][(C₁-C₄)alkyl], NH(CO)(C₁-C₄)alkyl, NH(CO)(C₁-C₄)alkyl-NH₂, NH(CO)(C₆-C₁₀)aryl, NHSO₂(C₁-C₄)alkyl, SO₂NH₂, and CF₃.

9. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein L-R⁴ is selected from:

10. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein R⁵ represents hydrogen.

11. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein R⁵ represents methyl.

12. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein R² represents amino.

13. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein R² represents hydrogen.

14. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein R² represents hydrogen;

and R³ represents hydrogen, methyl, trifluoromethyl or benzyl.

15. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein

Z and E represent carbon;

Y, D, and A represent nitrogen;

L represents a bond or C₂ alkyl;

R² represents hydrogen;

R³ represents hydrogen or methyl;

R⁴ represents a heteroaryl selected from indolyl, indazolyl, benzimidazolyl, or indolinonyl, said heteroaryl optionally substituted with one or two substituents selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, (C₁-C₄)alkyl, (C₁-C₄)alkyl(C₂-C₉)heterocyclyl, (C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl(CO)O(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH₂, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl-OH, (C₁-C₄)alkyl-O(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(C₆-C₁₀)aryl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-O(CO)(C₆-C₁₀)aryl, (C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(C₁-C₄)alkyl, (C₁-C₄)alkyl-N[(C₁-C₄)alkyl][(C₁-C₄)-alkyl], (C₁-C₄)alkyl-NH(CO)(C₁-C₄)alkyl , (C₁-C₄)alkyl-NH(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(CO)(C₆-C₁₀)aryl , (C₁-C₄)alkyl(CN), (C₁-C₄)alkyl(C₆-C₁₀)aryl, (CO)OH, (CO)O(C₁-C₄)alkyl , (CO)NH₂, (CO)NH(C₁-C₄)alkyl, (CO)NH(C₁-C₄)alkyl(CO)OH, (CO)(C₁-C₄)alkyl, (CO)(C₁-C₄)alkyl (C₆-C₁₀)aryl, (CO)(C₁-C₄)alkyl(C₁-C₉)heteroaryl, (CO)(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, (CO)(C₂-C₉)heterocyclyl, (CO)(C₆-C₁₀)aryl, (CO)(C₁-C₉)heteroaryl, (C₆-C₁₀)aryl, (C₆-C₁₀)aryl-halogen, (C₆-C₁₀)aryl-OH, (C₆-C₁₀)aryl-NH₂, (C₆-C₁₀)aryl-O(C₁-C₄)alkyl, (C₁-C₉)heteroaryl , (C₁-C₉)heteroaryl-halogen, (C₁-C₉)heteroaryl-OH, (C₁-C₉)heteroaryl-NH₂, (C₁-C₉)heteroaryl(C₁-C₄)alkyl, (C₁-C₉)heteroaryl-O(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-NH₂, O(C₁-C₄)alkyl, O(C₁-C₄)alkyl (C₆-C₁)aryl, O(C₁-C₄)alkyl(C₆-C₁₀)heteroaryl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, O(EtO)_1-3H, O (EtO )_1-3(C₁-C₄)alkyl, O(C₆-C₁₀)aryl, O(CO)(C₁-C₄)alkyl, O(CO)(C₁-C₄)alkyl-NH₂, O(CO)(C₆-C₁₀)aryl, OCF₃, OSO₂(C₁-C₄)alkyl, OSO₂OH, NH(C₁-C₄)alkyl, N[C₁-C₄)alkyl][(C₁-C₄)alkyl], NH(CO)(C₁-C₄)alkyl, NH(CO)(C₁ -C₄)alkyl-NH₂, NH(CO)(C₆-C₁₀)aryl, NHSO₂(C₁-C₄)alkyl, SO₂NH₂, and CF₃; and

R⁵ represents hydrogen or methyl.

16. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein

Z and D represent carbon;

Y, E and A represent nitrogen;

L represents a bond or C₂ alkyl;

R¹ represents hydrogen;

R² represents hydrogen;

R³ represents hydrogen or methyl;

R⁴ represents a heteroaryl selected from indolyl, indazolyl, benzimidazolyl, or indolinonyl, said heteroaryl optionally substituted with one or two substituents selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, (C₁-C₄)alkyl, (C₂-C₉)heterocyclyl, (C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl(CO)O(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH₂, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl-OH, (C₁-C₄)alkyl-O(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(C₆-C₁₀)aryl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-O(CO)(C₆-C₁₀)aryl, (C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH((C₁-C₄)alkyl, (C₁C₄)alkyl-N[(C₁C₄)alkyl][(C₁-C₄)-alkyl], (C₁-C₄)alkyl-NH(CO)(C₁-C₄)alkyl, (C₁-C₄)alkyl-NH(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(CO)(C₆-C₁₀)aryl, (C₁-C₄)alkyl(CN), (C₁-C₄)alkyl(C₆-C₁₀)aryl, (CO)OH, (CO)O(C₁-C₄)alkyl, (CO)NH₂, (CO)NH(C₁-C₄)alkyl, (CO)NH(C₁-C₄)alkyl(CO)OH, (CO)(C₁-C₄)alkyl, (CO)(C₁-C₄)alkyl(C₆-C₁₀)aryl, (CO)(C₁-C₄)alkyl(C₁-C₉)heteroaryl, (CO)(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, (CO)(C₂-C₉)heterocyclyl, (CO)(C₆-C₁₀)aryl, (CO)(C₁-C₉)heteroaryl, (C₆-C₁₀)aryl, (C₆-C₁₀)aryl-halogen, (C₆-C₁₀)aryl-OH, (C₆-C₁₀)aryl-NH₂, (C₆-C₁₀)aryl-O (C₁-C₄)alkyl, (C₁-C₉)heteroaryl, (C₁-C₉)heteroaryl-halogen, (C₁-C₉)heteroaryl-OH, (C₁-C₉)heteroaryl-NH₂, (C₁-C₉)heteroaryl(C₁-C₄)alkyl, (C₁-C₉)heteroaryl-O(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-NH₂, O(C₁-C₄)alkyl, O(C₁-C₄)alkyl(C₆-C₁₀)aryl, O(C₁-C₄)alkyl(C₆-C₁₀)heteroaryl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, O (EtO )_1-3H, O (EtO )_1-3(C₁-C₄)alkyl, O(C₆-C₁₀)aryl, O(CO)(C₁-C₄)alkyl, O(CO)(C₁-C₄)alkyl-NH₂, O(CO)(C₆-C₁₀)aryl, OCF₃, OSO₂(C₁-C₄)alkyl, OSO₂OH, NH(C₁-C₄)alkyl, N[(C₁-C₄)alkyl][(C₁-C₄)alkyl], NH(CO)(C₁-C₄)alkyl, NH(CO)(C₁-C₄)alkyl-NH₂, NH(CO)(C₆-C₁₀)aryl, NHSO₂(C₁-C₄)alkyl, SO₂NH₂, and CF₃; and

R⁵ represents hydrogen or methyl.

17. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein

Y and E represent carbon;

Z, D, and A represent nitrogen;

L represents a bond or C₂ alkyl;

R² represents hydrogen;

R³ represents hydrogen or methyl;

R⁴ represents a heteroaryl selected from indolyl, indazolyl, benzimidazolyl, or indolinonyl, said heteroaryl optionally substituted with one or two substituents selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, (C₁-C₄)alkyl, (C₁-C₄)alkyl(C₂-C₉)heterocyclyl, (C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl(CO)O(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH₂, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl-OH, (C₁-C₄)alkyl-O(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(C₆-C₁₀)aryl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl, (C₁C₄)alkyl-O(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-O(CO)(C₆-C₁₀)aryl, (C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(C₁-C₄)alkyl , (C₁-C₄)alkyl-N[(C₁-C₄)alkyl][(C₁-C₄)-alkyl], ((C₁-C₄)alkyl-NH(CO)(C₁-C₄)alkyl, (C₁-C₄)alkyl-NH(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(CO)(C₆-C₁₀)aryl, (C₁-C₄)alkyl(CN), (C₁-C₄)alkyl(C₆-C₁₀)aryl, (CO)OH, (CO)O(C₁-C₄)alkyl, (CO)NH₂, (CO)NH(C₁-C₄)alkyl, (CO)NH(C₁-C₄)alkyl(CO)OH, (CO)(C₁-C₄)alkyl, (CO)(C₁-C₄)alkyl(C₆-C₁₀)aryl, (CO)(C₁-C₄)alkyl(C₁-C₉)heteroaryl, (CO)(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, (CO)(C₂-C₉)heterocyclyl, (CO)(C₆-C₁₀)aryl, (CO)(C₁-C₉)heteroaryl, (C₆-C₁₀)aryl, (C₆-C₁₀)aryl-halogen, (C₆-C₁₀)aryl-OH, (C₆-C₁₀)aryl-NH₂, (C₆-C₁₀)aryl-O(C₁-C₄)alkyl, (C₁-C₉)heteroaryl, (C₁-C₉)heteroaryl-halogen, (C₁-C₉)heteroaryl-OH, (C₁-C₉)heteroaryl-NH₂, (C₁-C₉)heteroaryl(C₁-C₄)alkyl, (C₁-C₉)heteroaryl-O(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-NH₂, O(C₁-C₄)alkyl, O(C₁-C₄)alkyl(C₆-C₁₀)aryl, O(C₁-C₄)alkyl (C₆-C₁₀)heteroaryl , O(C₁-C₄)alkyl (C₂-C₉)heterocyclyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, O(EtO )_1-3H, O(EtO )_1-3(C₁-C₄)alkyl, O(C₆-C₁₀)aryl, O(CO)(C₁-C₄)alkyl, O(CO)(C₁-C₄)alkyl-NH₂, O(CO)(C₆-C₁₀)aryl, OCF₃, OSO₂(C₁-C₄)alkyl , OSO₂OH, NH(C₁-C₄)alkyl, N[(C₁-C₄)alkyl][(C₁-C₄)alkyl], NH(CO)(C₁-C₄)alkyl, NH(CO)(C₁-C₄)alkyl-NH₂, NH(CO)(C₆-C₁₀)aryl, NHSO₂(C₁-C₄)alkyl, SO₂NH₂, and CF₃; and

R⁵ represents hydrogen or methyl.

18. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein

Y and D represent carbon;

Z, E and A represent nitrogen;

L represents a bond or C₂ alkyl;

R^I represents hydrogen;

R² represents hydrogen;

R³ represents hydrogen or methyl;

R⁴ represents a heteroaryl selected from indolyl, indazolyl, benzimidazolyl, or indolinonyl, said heteroaryl optionally substituted with one or two substituents selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, (C₁-C₄)alkyl, (C₁-C₄)alkyl(C₂-C₉)heterocyclyl, (C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl(CO)O(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH₂, (C₁-C₄)alkyl (CO)NH(C₁-C₄)alkyl, (C₁-C₄)alkyl(CO)NH(C₁-C₄)alkyl(CO)OH, (C₁-C₄)alkyl-OH, (C₁-C₄)alkyl-O(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(C₆-C₁₀)aryl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl, (C₁-C₄)alkyl-O(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-O(CO)(C₆-C ₁₀)aryl, (C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(C₁-C₄)alkyl, (C₁-C₄)alkyl-N[(C₁-C₄)alkyl][(C₁-C₄)alkyl], (C₁C₄)alkyl-NH(CO)(C₁-C₄)alkyl, (C₁-C₄)alkyl-NH(CO)(C₁-C₄)alkyl-NH₂, (C₁-C₄)alkyl-NH(CO)(C₆-C₁₀)aryl, (C₁-C₄)alkyl(CN), (C₁-C₄)alkyl(C₆-C₁₀)aryl, (CO)OH, (CO)O(C₁-C₄)alkyl, (CO)NH₂, (CO)NH(C₁-C₄)alkyl, (CO)NH(C₁-C₄)alkyl(CO)OH, (CO)(C₁-C₄)alkyl, (CO)(C₁-C₄)alkyl (C₆-C₁₀)aryl, (CO)(C₁-C₄)alkyl(C₁-C₉)heteroaryl, (CO)(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, (CO)(C₂-C₉)heterocyclyl, (CO)(C₆-C₁₀)aryl, (CO)(C₁-C₉)heteroaryl, (C₆-C₁₀)aryl, (C₆-C₁₀)aryl-halogen, (C₆-C₁₀)aryl-OH, (C₆-C₁₀)aryl-NH₂, (C₆-C₁₀)aryl-O(C₁-C₄)alkyl, (C₁-C₉)heteroaryl, (C₁-C₉)heteroaryl-halogen, (C₁-C₉)heteroaryl-OH, (C₁-C₉)heteroaryl-NH₂, (C₁-C₉)heteroaryl(C₁-C₄)alkyl, (C₁-C₉)heteroaryl-O(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, (C₂-C₉)heterocyclyl(C₁-C₄)alkyl-NH₂, O(C₁-C₄)alkyl, O(C₁-C₄)alkyl(C₆-C₁₀)aryl, O(C₁-C₄)alkyl(C₆-C₁₀)heteroaryl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl, O(C₁-C₄)alkyl(C₂-C₉)heterocyclyl(C₁-C₄)alkyl-OH, O(EtO )_1-3H, O(EtO )_1-3(C₁-C₄)alkyl, O(C₆-C₁₀)aryl, O(CO)(C₁-C₄)alkyl, O(CO)(C₁-C₄)alkyl-NH₂, O(CO)(C₆-C₁₀)aryl, OCF₃, OSO₂(C₁-C₄)alkyl, OSO₂OH, NH(C₁-C₄)alkyl, N[(C₁-C₄)alkyl][(C₁-C₄)alkyl], NH(CO)(C₁-C₄)alkyl, NH(CO)(C₁-C₄)alkyl-NH₂, NH(CO)(C₆C₁₀)aryl, NHSO₂(C₁-C₄)alkyl, SO₂NH₂, and CF₃; and

R⁵ represents hydrogen or methyl.

19. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein

Z represents carbon or nitrogen;

Y represents carbon or nitrogen, wherein one of Z and Y represents nitrogen;

A, D and E is selected from carbon or nitrogen, wherein

A and D represent nitrogen and E represents carbon;

or A and E represent nitrogen and D represents carbon;

or E represents nitrogen and A and D represent carbon;

R¹ represents hydrogen or methyl, when D represents carbon, and R¹ is absent when D represents nitrogen;

R² represents hydrogen or amino;

R³ represents hydrogen, methyl, trifluoromethyl or (C₀-C₁)alkylaryl;

R⁵ represents hydrogen or methyl;

L-R⁴ is selected from the group consisting of;

20. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, wherein when A is nitrogen, L represents a bond or (C₂)alkyl.

21. The compound or pharmaceutically acceptable solvate or salt thereof according to claim 1, said compound being selected from the group consisting of:

N⁴(1H-indol -5-ylmethyl)-N²41H-indol-4-yppyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-(1H-indol-4-yppyrimidine-2,4-diamine;

N⁴-(1H-indol-5-ylmethyl)-N²(methyl-1H-indol -5-yl)pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²(1H-indazol-5yl-)pyrimidine-2,4-diamine;

N²-[2(1H-indol -3yl)ethyl]-N⁴(1H-indol-5-ylmethyl)pyrimidine-2,4-diamine;

3-{2[4-(1H-indol -5-ylmethylamino)-pyrimidin-2ylamino]ethyl}-1H-indol -5-ol;

N⁴-(1H-indol -5-ylmethyl)-N²[2(5-methyl-1H-indol -3yl)ethyl]pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²[2(5-methoxy-1H-indol-3yl)ethyl]pyrimidine-2,4-diamine;

N²-(1H-indol-4-yl)-N⁴(2-methyl-1H-indol-5ylmethyl)pyrimidine-2,4-diamine;

N²(1H-indol-3-yl)-ethyl)-N⁴(2-methyl-1H-indol -5ylmethyl)pyrimidine-2,4-diamine;

N²(1H-indol-4-yl)-N⁴-(1H-indazol-5ylmethyl)pyrimidine-2,4-diamine;

N⁴-(1H-benzo[d]imidazol-5-ylmethl)-N²(1H-indol-4- yl)pyrimidine-2,4-diamine;

N⁴(1H-indol -6-ylmethyl)-N²(1H-indol-4-yl)pyrimidine-2,4-diamine;

N²(1H-indol -5-ylmethyl)-N⁴-(1H-indol-4-yl)pyrimidine-2,4-diamine;

N²-(1H-indol -5-ylmethyl)-N⁴(2methyl-1H-indol -5-yl)pyrimidine-2,4-diamine;

N⁴[2-(1H-indol -3yl)ethyl]-N²(1H-indol-5-ylmethyl)pyrimidine-2,4-diamine;

3-{2-[2-(1H-indol -5-ylmethylamino)-pyrimidin-4-ylamino]ethyl}-1H-indol -5-ol;

N²(1H-indol -5-ylmethyl)-N⁴-[2(5-methyl-1H-indol -3yl)ethyl]pyrimidine-2,4-diamine;

N²(1H-indol -5-ylmethyl)-N⁴-[2(5-methoxy-1H-indol-3-yl)ethyl]pyrimidine-2,4-diamine;

N²-(1H-indazol-5 -ylmethyl)-N⁴-(1H-indol-4-yl)pyrimidine-2,4-diamine;

N²-(1H-indol -4-yl)-N⁴-(1H-indol -5ylmethyl)-6-methylpyrimidine-2,4-diamine;

3-{2[4(1H-indol -5 -ylmethylamino)-6-methyl-pyrimidin-2-ylamino]ethyl}-1H-indol -5-ol;

N⁴-(1H-indol -5 -ylmethyl)-N²-(2-methyl- 1H-indol -5 -yl)-6-trifluoromethylpyrimidine-2,4-diamine;

N²-(2-(1H-indol -3yl)ethyl)-N⁴-(1H-indol-5-ylmethyl)-6-trifluoromethylpyrimidine-2,4-diamine;

N⁴-(1H-indazol-5-ylmethyl)-N²-(1H-indol-4-yl)-6-methylpyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-(1H-indol -4-yl)pyrimidine-2,4,5-triamine;

N⁴-(1H-indol-5-ylmethyl)-N²-(1H-indol-5-yl)pyrimidine-2,4,5-triamine;

N⁴-(1H-indol -5-ylmethyl)-N²-(1H-indol-6-yl)pyrimidine-2,4,5-triamine;

N⁴-(2-methyl-1H-indol -5-yl)-N²-(2-methyl- 1H-indol -5-ylmethyl)pyrimidine-2,4-diamine;

N²-[2-(5-methoxy- 1H-indol -3-ypethyl]-N⁴-(2-methyl- 1H-indol -5-ylmethyl)pyrimidine-2,4-diamine;

N²-(1H-indazo1-5-ylmethyl)-N⁴-(2-methyl- 1H-indol -5-yl)pyrimidine-2,4-diamine;

N⁴-(1H-indazol-5-ylmethyl)-N²-[2-(5-methoxy- 1H-indol-3-yl)ethyl]pyrimidine-2,4-diamine;

N²-(1H-benzo [d]imidazol-5-ylmethyl)-N⁴-(2-methyl- 1 H-indol -5-yl)pyrimidine-2,4-diamine;

N⁴-(1H-benzo [d]imidazol-5-ylmethyl)-N²-[2-(5 -methoxy- 1H-indol -3-Yl)ethyl]pyrimidine-2,4-diamine;

N²-(1H-indol -6-ylmethyl)-N⁴-(2-methyl- 1H-indol -5 -yl)pyrimidine-2,4-diamine;

N⁴-(1H-indol -6-ylmethyl)-N²-[2-(5-methoxy- 1H-indol -3-yl)ethyl]pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²- {2-[5-(benzyloxy)- 1H-indol -3-yl]ethyl}pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-{2-[5-(2-morpholinoethoxy)- 1H-indol -3-yl]ethyl}pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-{2-[5-(2-methoxyethoxy)- 1H-indol -3-yl]ethyl}pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-(1-methyl- 1H-indol -4-yl)pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-(1H-indazol-4-yl)pyrimidine-2,4-diamine;

Methyl 4-[4-(1H-indol -5-ylmethylamino)pyrimidin-2-ylamino]- 1H-indole-6-carboxylate;

N²-(1H-indol -5-ylmethyl)-N⁴-(1H-indol-5-yl)pyrimidine-2,4-diamine;

N²-(1H-indol -5-ylmethyl)-6-methyl-N⁴-(2-methyl- 1H-indol -5-yl)pyrimidine-2,4-diamine;

N⁴-(1H-indol-5-ylmethyl)-N²-[2-(5-methoxy-1H-indol-3yl)ethyl]-6-methylpyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-6-benzyl-N²-[2-(5-methoxy- 1H-indol-3-yl)ethyl]pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-[2-(5-methoxy-7-methyl-1H-indol -3yl)ethyl]pyrimidine-2,4-diamine;

N⁴-(1H-indol -5 -ylmethyl)-N²-[2-(5-ethoxy- 1H-indol-3-yl)ethyl]pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-{[2-(trifluoromethoxy)- 1H-indol -3yl]ethyl}pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²[2-(5-fluoro-1H-indol-3-yl)ethyl]pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-[2-(6-methoxy- 1H-indol-3-yl)ethyl]pyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-[2-(7-methoxy- 1H-indol-3-yl)ethyl]pyrimidine-2,4-diamine;

N²-(1H-indol -5-ylmethyl)-N⁴-(1,2-dimethyl- 1H-indol -5-yl)pyrimidine-2,4-diamine;

methyl 5-[2-(1H-indol -5-ylmethylamino)pyrimidin-4-ylamino]-1H-indole-2-carboxylate;

N²-(1H-indol -5-ylmethyl)-N⁴-(2,3-dimethyl-1H-indol -5-yl)pyrimidine-2,4-diamine;

N²-(1H-indol -5-ylmethyl)-N⁴-(1H-benzo[d]imidazol-5yl)pyrimidine-2,4-diamine;

N²-(1H-indol -5-ylmethyl)-N⁴-(2-methyl-1H-benzo[d]imidazol-5-yl)pyrimidine-2,4-diamine;

N⁴-(1H-indol -5 -ylmethyl)-N²-(1H-indazol-4-yl)-6-methylpyrimidine-2,4-diamine;

N²-[2-(5-methoxy- 1H-indol -3yl)ethyl]-6-methyl-N⁴-[(2-methyl- 1H-indol -5-yl)methyl]pyrimidine-2,4-diamine;

N⁴-(1H-indazol-5-ylmethyl)-N²-[2-(5-methoxy- 1 H-indol-3yl)ethyl]-6-methylpyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-[2-(5-methoxy-2-methyl-1H-indol-3yl)ethyl]-6- methylpyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-[2-(4-methoxy- 1H-indol-3yl)ethyl]pyrimidine-2,4-diamine;

4-[4-(1H-indol -5-ylmethylamino)pyrimidin-2-ylamino]- 1 H-indole-6-carboxylic acid;

N²-(1H-indol -4-yl)-6-methyl-N⁴-[(2-methyl- 1H-indol -5-yl)methyl]pyrimidine-2,4-diamine;

{5-[2-(1H-indol -5-ylmethylamino)pyrimidin-4-ylamino]- 1H-indol -2-yl }methanol;

N²-(1H-indol -5 -ylmethyl)-N⁴-methyl-N⁴-(2-methyl- 1H-indol -5-yl)pyrimidine-2,4-diamine;

N²-(1H-indol -5-ylmethyl)-N⁴-(1,2-dimethyl- 1H-indol -5-yl)-N⁴-methylpyrimidine-2,4-diamine;

N⁴-(1H-indol -5-ylmethyl)-N²-[2-(5-methoxy- 1-methyl- 1H-indol-3-yl)ethyl]pyrimidine-2,4-diamine;

N⁴-(1H-indol-5-ylmethyl)-N²-[2-(5-methoxy- 1-methyl-1 H-indol-3 -yl)ethyl]-N²-methylpyrimidine-2,4-diamine; and

N⁴-(1H-indol -5-ylmethyl)-N²-[2-(5-methoxy- 1H-indol -3yl)ethyl]-N²-methylpyrimidine-2,4-diamine.

22. A pharmaceutical composition comprising the compound or pharmaceutically acceptable solvate or salt thereof according to claim 1 together with a pharmaceutically acceptable diluent or carrier.

23. A method for treatment of colon cancer or breast cancer, which comprises administering to a subject in need thereof, a therapeutically effective amount of the compound or pharmaceutically acceptable solvate or salt thereof according to claim 1.