Claims for Patent: 7,855,211

Summary for Patent: 7,855,211

Title:	Protein kinase inhibitors
Abstract:	The present invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof which is useful in the treatment of cell proliferative diseases.
Inventor(s):	David A Coates, Lawrence Mark Gelbert, John M. KNOBELOCH, Alfonso DE DIOS MAGANA, Ana DE PRADO GONZALEZ, Miriam FILADELFA DEL PRADO CATALINA, Maria Cristina GARCIA PAREDES, Eva Maria Martin De La Nava, Maria Dolores MARTIN ORTEGA FINGER, Jose Antonio Martinez Perez, Ana Isabel Mateo Herranz, Carlos PEREZ MARTINEZ, Concepcion SANCHEZ MARTINEZ
Assignee:	Eli Lilly and Co
Application Number:	US12/637,789
Patent Claims:	1. A compound of formula (I): wherein, R1 is C3-C5 alkyl, C3-C5 cycloalkyl or cyclopropyl-methyl; R2 and R3 are H or fluorine, wherein at least one of R2 or R3 is fluorine; R4 is H or CH3; R5 is C1-C6 alkyl or —NR6R7 wherein R6 and R7 are each C1-C3 alkyl; Q is CH2, O, S or a direct bond; and W and Y are C or N, wherein at least one of W or Y is N and wherein when Q is O or S, W is C; or a pharmaceutically acceptable salt thereof. 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is isopropyl, cyclopropyl, cyclopentyl or cyclopropyl-methyl. 3. The compound according to claim 2, or a pharmaceutically acceptable salt thereof, wherein R1 is isopropyl. 4. The compound according to claim 3, or a pharmaceutically acceptable salt thereof, wherein R2 and R3 are each fluorine. 5. The compound according to claim 4, or a pharmaceutically acceptable salt thereof, wherein R5 is C1-C3 alkyl. 6. The compound according to claim 2, or a pharmaceutically acceptable salt thereof, wherein R5 is —NR6R7 wherein R6 and R7 are each ethyl. 7. The compound according to claim 5, or a pharmaceutically acceptable salt thereof, wherein Q is CH2 or a direct bond. 8. The compound according to claim 7, or a pharmaceutically acceptable salt thereof, wherein Y is N. 9. The compound according to claim 8, or a pharmaceutically acceptable salt thereof, wherein R4 is H. 10. The compound according to claim 9, or a pharmaceutically acceptable salt thereof, wherein Q is CH2. 11. The compound according to claim 10, or a pharmaceutically acceptable salt thereof, wherein W is N. 12. The compound according to claim 11 which is: or a pharmaceutically acceptable salt thereof. 13. The compound according to claim 12 which is the mesylate salt. 14. [5-(4-Ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzoimidazol-5-yl)-pyrimidin-2-yl]-amine crystalline form III, characterised by an X-ray powder diffraction pattern (CuKα radiation, λ=1.54056 Å) comprising a peak at 21.29 (2θ±0.1°) and optionally one or more peaks selected from the group comprising 11.54, 10.91, and 12.13 (2θ±0.1°). 15. [5-(4-Ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzoimidazol-5-yl)-pyrimidin-2-yl]-amine crystalline form III as claimed in claim 14 which is further characterised by a 13C NMR spectrum comprising chemical shift peaks ν(F1) [ppm] at 112.7, 127.3 and 129.4. 16. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of: 17. A pharmaceutical formulation comprising a compound of formula (I): wherein, R1 is C3-C5 alkyl, C3-C5 cycloalkyl or cyclopropyl-methyl; R2 and R3 are H or fluorine, wherein at least one of R2 or R3 is fluorine; R4 is H or CH3; R5 is C1-C6 alkyl or —NR6R7 wherein R6 and R7 are C1-C3 alkyl; Q is CH2, O, S or a direct bond; and W and Y are C or N, wherein at least one of W or Y is N and wherein when Q is O or S, W is C; or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 18. The pharmaceutical formulation according to claim 17 comprising the compound of formula (I) wherein, R1 is isopropyl, R2 and R3 are each fluorine, R5 is C1-C3 alkyl, and Q is CH2 or a direct bond, or a pharmaceutically acceptable salt thereof. 19. The pharmaceutical formulation according to claim 18 comprising the compound which is: or a pharmaceutically acceptable salt thereof. 20. The pharmaceutical formulation according to claim 17 comprising the compound which is [5-(4-Ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzoimidazol-5-yl)-pyrimidin-2-yl]-amine crystalline form III, characterised by an X-ray powder diffraction pattern (CuKα radiation, λ=1.54056 Å) comprising a peak at 21.29 (2θ±0.1°) and optionally one or more peaks selected from the group comprising 11.54, 10.91, and 12.13 (2θ±0.1°), or a pharmaceutically acceptable salt thereof. 21. A method of treating cancer selected from the group consisting of colorectal cancer, breast cancer, lung cancer, prostate cancer, glioblastoma, mantel cell lymphoma, chronic myeloid leukaemia and acute myeloid leukaemia in a mammal comprising administering to a mammal in need of such treatment an effective amount of a compound of formula (I): wherein, R1 is C3-C5 alkyl, C3-C5 cycloalkyl or cyclopropyl-methyl; R2 and R3 are H or fluorine, wherein at least one of R2 or R3 is fluorine; R4 is H or CH3; R5 is C1-C6 alkyl or —NR6R7 wherein R6 and R7 are C1-C3 alkyl; Q is CH2, O, S or a direct bond; and W and Y are C or N, wherein at least one of W or Y is N and wherein when Q is O or S, W is C; or a pharmaceutically acceptable salt thereof. 22. The method according to claim 21 comprising the compound of formula (I) wherein, R1 is isopropyl, R2 and R3 are each fluorine, R5 is C1-C3 alkyl, and Q is CH2 or a direct bond, or a pharmaceutically acceptable salt thereof. 23. The method according to claim 22 comprising the compound which is: or a pharmaceutically acceptable salt thereof.