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): ##STR00001## or a pharmaceutically acceptable salt thereof which is useful in the treatment of cell proliferative diseases.
Inventor(s):	Coates; David A (Indianapolis, IN), Gelbert; Lawrence Mark (Indianapolis, IN), Knobeloch; John M. (Indianapolis, IN), De Dios Magana; Alfonso (Carmel, IN), De Prado Gonzalez; Ana (Madrid, ES), Filadelfa Del Prado Catalina; Miriam (Madrid, ES), Garcia Paredes; Maria Cristina (Madrid, ES), Martin De La Nava; Eva Maria (Madrid, ES), Martin Ortega Finger; Maria Dolores (Madrid, ES), Martinez Perez; Jose Antonio (Madrid, ES), Mateo Herranz; Ana Isabel (Madrid, ES), Perez Martinez; Carlos (Madrid, ES), Sanchez Martinez; Concepcion (Madrid, ES)
Assignee:	Eli Lilly and Company (Indianapolis, IN)
Application Number:	12/637,789
Patent Claims:	1. A compound of formula (I): ##STR00038## wherein, R1 is C.sub.3-C.sub.5 alkyl, C.sub.3-C.sub.5 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 CH.sub.3; R5 is C.sub.1-C.sub.6 alkyl or --NR6R7 wherein R6 and R7 are each C.sub.1-C.sub.3 alkyl; Q is CH.sub.2, 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 C.sub.1-C.sub.3 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 CH.sub.2 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 CH.sub.2. 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: ##STR00039## 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 (CuK.alpha. radiation, .lamda.=1.54056 .ANG.) comprising a peak at 21.29 (2.theta..+-.0.1.degree.) and optionally one or more peaks selected from the group comprising 11.54, 10.91, and 12.13 (2.theta..+-.0.1.degree.). 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 .sup.13C NMR spectrum comprising chemical shift peaks .nu.(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: ##STR00040## ##STR00041## ##STR00042## ##STR00043## 17. A pharmaceutical formulation comprising a compound of formula (I): ##STR00044## wherein, R1 is C.sub.3-C.sub.5 alkyl, C.sub.3-C.sub.5 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 CH.sub.3; R5 is C.sub.1-C.sub.6 alkyl or --NR6R7 wherein R6 and R7 are C.sub.1-C.sub.3 alkyl; Q is CH.sub.2, 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 C.sub.1-C.sub.3 alkyl, and Q is CH.sub.2 or a direct bond, or a pharmaceutically acceptable salt thereof. 19. The pharmaceutical formulation according to claim 18 comprising the compound which is: ##STR00045## 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-i- sopropyl-2-methyl-3H-benzoimidazol-5-yl)-pyrimidin-2-yl]-amine crystalline form III, characterised by an X-ray powder diffraction pattern (CuK.alpha. radiation, .lamda.=1.54056 .ANG.) comprising a peak at 21.29 (2.theta..+-.0.1.degree.) and optionally one or more peaks selected from the group comprising 11.54, 10.91, and 12.13 (2.theta..+-.0.1.degree.), 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): ##STR00046## wherein, R1 is C.sub.3-C.sub.5 alkyl, C.sub.3-C.sub.5 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 CH.sub.3; R5 is C.sub.1-C.sub.6 alkyl or --NR6R7 wherein R6 and R7 are C.sub.1-C.sub.3 alkyl; Q is CH.sub.2, 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 C.sub.1-C.sub.3 alkyl, and Q is CH.sub.2 or a direct bond, or a pharmaceutically acceptable salt thereof. 23. The method according to claim 22 comprising the compound which is: ##STR00047## or a pharmaceutically acceptable salt thereof.