Dihydropyrazolo[1,5-A]pyrimidine and dihydroimidazo[1,5-A]pyrimidine derivatives and methods of use thereof

Abstract

The present invention relates to dihydropyrazolo[1,5-a]pyrimidine and dihydroimidazo[1,5-a]pyrimidine derivatives, compositions comprising an effective amount of a dihydropyrazolo[1,5-a]pyrimidine or a dihydroimidazo[1,5-a]pyrimidine derivative and methods for treating or preventing cancer, comprising administering to a subject in need thereof an effective amount of a dihydropyrazolo[1,5-a]pyrimidine or a dihydroimidazo[1,5-a]pyrimidine derivative.

Description

Claims

1. A compound of Formula (I):

2. A composition comprising an effective amount of a compound or claim 1 or a pharmaceutically acceptable salt of the compound of claim 1 and a physiologically acceptable vehicle.

3. A method of treating, inhibiting the growth of, or eradicating neoplasms in a mammal in need thereof which comprises providing to said mammal an effective amount of a compound of claim 1 or a composition of claim 2.

4. The method of treating cancer in a mammal in need thereof which comprises providing to said mammal an effective amount of a compound of claim 1 or a composition of claim 2.

5. The method of claim 4 wherein the cancer is selected from the group consisting of breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, lung, pancreas, skin, liver, prostate and brain.

6. The method of claim 4, wherein the mammal is human.

7. The compound of claim 1, wherein the compound is: N-[3-(4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-3-(trifluoromethyl)benzamide.

8. The compound of claim 1, wherein the compound is: N-{3-[4-(methylsulfonyl)-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl]phenyl}-3-(trifluoromethyl)benzamide or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1, wherein the compound is: methyl 7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidine-4(5H)-carboxylate or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1, wherein the compound is: ethyl 7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidine-4(5H)-carboxylate or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1, wherein the compound is: N-isopropyl-7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidine-4(5H)-carboxamide or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1, wherein the compound is: tert-butyl 7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidine-4(5H)-carboxylate or a pharmaceutically acceptable salt thereof.

13. The compound of claim 1, wherein the compound is: N-[3-(4-but-2-yn-1-yl-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-3-(trifluoromethyl)benzamide or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1, wherein the compound is: ethyl 7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylate or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1, wherein the compound is: N-ethyl-7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidine-4(5H)-carboxamide or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1, wherein the compound is: N-[3-(4-acetyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-3-(trifluoromethyl)benzamide or a pharmaceutically acceptable salt thereof.

17. The compound of claim 1, wherein the compound is: ethyl 4-acetyl-7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylate or a pharmaceutically acceptable salt thereof.

18. The compound of claim 1, wherein the compound is: tert-butyl 7-(3-{(tert-butoxycarbonyl)[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidine-4(5H)-carboxylate 4(5H)-carboxylate or a pharmaceutically acceptable salt thereof.

19. The compound of claim 1, wherein the compound is: 3-ethyl 4-methyl 7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidine-3,4(5H)-dicarboxylate or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1, wherein the compound is: tert-butyl {2-oxo-2-[7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl]ethyl}carbamate or a pharmaceutically acceptable salt thereof.

21. The compound of claim 1, wherein the compound is: N-[3-(4-glycyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-3-(trifluoromethyl)benzamide or a pharmaceutically acceptable salt thereof.

22. The compound of claim 1, wherein the compound is: N-{3-[4-(N-acetylglycyl)-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl]phenyl}-3-(trifluoromethyl)benzamide or a pharmaceutically acceptable salt thereof.

23. The compound of claim 1, wherein the compound is: tert-butyl {3-oxo-3-[7-(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl]propyl}carbamate or a pharmaceutically acceptable salt thereof.

24. The compound of claim 1, wherein the compound is: N-[3-(4-β-alanyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-3-(trifluoromethyl)benzamide or a pharmaceutically acceptable salt thereof.

25. The compound of claim 1, wherein the compound is: N-{3-[4-(N-acetyl-β-alanyl)-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl]phenyl}-3-(trifluoromethyl)benzamide or a pharmaceutically acceptable salt thereof.

26. The compound of claim 1, wherein the compound is: N-[4-chloro-3-(4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-3-(trifluoromethyl)benzamide or a pharmaceutically acceptable salt thereof.