[1,3]DIAZINO[5,4-D]PYRIMIDINES AS HER2 INHIBITORS

Abstract

The present invention relates to novel [1,3]diazino[5,4-d]pyrimidines and derivatives of Formula (I) (see Formula) wherein groups R1, R2, R3 and R4 have the meanings provided in the claims and the descriptive memorandum, their use as inhibitors of HER2 and its mutants, pharmaceutical compositions containing such compounds and their use as medicaments, especially as agents for the treatment and / or prevention of oncological diseases.

Claims

1. A compound of Formula (I), or a salt thereof, ^77^ iη / ZZΖΠZΖ / E / YILI characterized in that R1 is selected from the group consisting of hydrogen, -CH3, -CCH, -OCH3 and halogen; R2 is hydrogen or halogen; R3 is selected from the group consisting of Formulas (i.1), (i.2), (i.3) and (i.4); R4b wherein Q denotes a 4-6 membered heterocycle containing 1 N atom, wherein one ring carbon atom is optionally substituted with methyl; Z denotes a 4-6 membered heterocycle containing 1 N atom, wherein one ring carbon atom is optionally substituted with methyl; R5 is -H or -CH3; and at least one of R1 and R2 is not hydrogen.

2. The compound according to claim 1, or a salt thereof, further characterized in that R1 is selected from the group consisting of -CH3, -CCH, -OCH3 and halogen.

3. The compound according to claim 1, a salt thereof, further characterized in that R1 is -CH3.

4. The compound according to claim 1, a salt thereof, further characterized in that R1 is-CCH.

5. The compound according to claim 1, a salt thereof, further characterized in that R1 is -OCH3.

6. The compound according to claim 1, a salt thereof, further characterized in that R1 is chlorine.

7. The compound according to claim 1, a salt thereof, further characterized in that R1 is fluorine.

8. The conformity compound further characterized in that R2 is hydrogen.

9. The conforming compound further characterized in that R2 is chlorine, with one or more of claims 1 and 7, and a salt thereof, 10. The compound according to any one or more of claims 1 or 9, a salt thereof, further characterized in that R4 is selected from the group consisting of R4a and R4b, wherein R4a is R4a·1 where R6 is -H or -CH3, n is 1 or 2; m is 1 or 2; and R4b is R4b·1 where p is 1 or 2; q is 1 or 2.

11. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, further characterized in that it is selected from the group consisting of Examples ΙΟΙ to 1-19; ^77^ ίη / ΖΖΠΖ / Ε / ΥΙΛΙ Ρ77Ρ ίη / ΖΖΠΖ / Ε / ΥΙΛΙ ίη / ΖΖΠΖ / Ε / ΥΙΛΙ 12. A pharmaceutical composition characterized in that it comprises a therapeutically effective amount of at least one compound of Formula (I) according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

13. The compound as claimed in one or more of claims 1 to 11, or a pharmaceutically acceptable salt thereof, for use as a medicament.

14. Use of the compound according to one or more of claims 1 to 11 to treat a patient having brain cancer, breast cancer, biliary cancer, bladder cancer, cervical cancer, colorectal cancer, endometrial cancer, skin cancer, esophageal cancer, head and neck cancer, gastrointestinal cancer, gallbladder cancer, kidney cancer, liver cancer, lung cancer or prostate cancer.

15. The pharmaceutical composition further characterized in that it comprises, in addition to a compound of Formula (I), a pharmaceutically active compound selected from the group consisting of a cytostatic active substance and a cytotoxic active substance.