Claims for Patent: 7,964,592

Summary for Patent: 7,964,592

Title:	2,4-di (phenylamino) pyrimidines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders
Abstract:	Novel pyrimidine derivatives of formula I to process for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.
Inventor(s):	Carlos Garcia-Echeverria, Takanori Kanazawa, Eiji Kawahara, Keiichi Masuya, Naoko Matsuura, Takahiro Miyake, Osamu Ohmori, Ichiro Umemura
Assignee:	Novartis AG
Application Number:	US10/549,250
Patent Claims:	1. A compound of formula I each of R0 or R2 independently is hydrogen, C1-C8alkyl, unsubstituted or substituted 5 or 6 membered heterocyclyl comprising 1 or 2 hetero atoms selected from N, O and S, C1-C8alkoxy, unsubstituted or substituted heterocyclyloxy, unsubstituted or substituted heterocyclylC1-C8alkoxy, unsubstituted or substituted amino, or halogen; R1 is hydrogen, C1-C8alkyl, haloC1-C8alkyl, unsubstituted or substituted 5 or 6 membered heterocyclyl comprising 1 or 2 hetero atoms selected from N, O and S, C1-C8alkoxy, unsubstituted or substituted heterocyclyloxy, unsubstituted or substituted HeterocyclylC1-C8alkoxy, unsubstituted or substituted amino, halogen; R3 is C1-C8alkylsulfinyl, C1-C8alkylsulfonyl, C5-C10 arylsulfonyl, or unsubstituted or substituted carbamoyl; R4 is hydrogen; R5 is chloro or bromo; R6 is hydrogen; each of R7 and R9 independently is hydrogen, C1-C8alkyl, haloC1-C8alkyl, unsubstituted or substituted C5-C10aryl, unsubstituted or substituted 5 or 6 membered heterocyclyl comprising 1 or 2 hetero atoms selected from N, O and S, C1-C8alkoxy, unsubstituted or substituted heterocyclyloxy, unsubstituted or substituted heterocyclylC1-C8alkoxy, unsubstituted or substituted amino, halogen, unsubstituted or substituted carbamoyl, or unsubstituted or substituted sulfamoyl; R8 is C5-C10aryl; unsubstituted or substituted 5 or 6 membered heterocyclyl comprising 1 or 2 hetero atoms selected from N, O and S; C5-C10aryloxy; unsubstituted or substituted heterocyclyloxy; or unsubstituted or substituted heterocyclylC1-C8alkoxy; and R10 is C1-C8alkyl, haloC1-C8alkyl, C1-C8alkoxy, unsubstituted or substituted heterocyclylC1-C8alkoxy, unsubstituted or substituted amino, or halogen; and A is C; or salts thereof. 2. The compound of claim 1, wherein each of R0, R1 or R2 is hydrogen. 3. The compound of claim 1, wherein R3 is C1-C8alkylsulfonyl, C5-C10arylsulfonyl or unsubstituted or substituted carbamoyl. 4. The compound of claim 1, wherein R3 is C1-C8alkylsulfonyl. 5. The compound of claim 1, wherein R3 is C5-C10arylsulfonyl. 6. The compound of claim 1, wherein R3 is unsubstituted or substituted carbamoyl. 7. The compound of claim 1, wherein R8 is piperidino, piperazino, N-methylpiperazino, morpholino, phenoxy, 1-methyl-4-piperidyloxy, 3-morpholinopropoxy, 2-morpholinoethoxy or 3-(N-methylpiperazino)-propoxy. 8. The compound of claim 1, wherein R8 is unsubstituted or substituted 5 or 6 membered heterocyclyl comprising 1 or 2 hetero atoms selected from N, O and S. 9. The compound of claim 1, wherein R0, R1 or R2 is hydrogen; R3 is C1-C8alkylsulfonyl; and R8 is unsubstituted or substituted 5 or 6 membered heterocyclyl comprising 1 or 2 hetero atoms selected from N, O and S. 10. The compound of claim 9, wherein R8 is piperidino, piperazino, N-methylpiperazino or morpholino. 11. The compound of claim 1, wherein said compound is selected from the group of compounds with the following names or formulae: 2-[5-chloro-2-(2-methoxy-4-morpholin-4-yl -phenylamino)-pyrimidin-4-ylamino]-N-methyl -benzamide; a compound of the formula wherein Rx has one of the meanings given in the following table: Compound No. Rx 7-1 7-2 7-3 7-4 7-5 7-7 7-8 7-9 7-10 7-11 7-12 7-13 7-14 7-17 7-18 7-20 7-21 7-25 7-26 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 8-2 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 9-1 9-2 9-3 9-4 9-5 9-6 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 10-1 10-2 10-3 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 11-1 11-2 11-4 a compound of the formula wherein Ry has one of the meanings given in the following table: Compound R 14-1 14-2 14-3 14-5 14-6 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 15-1 15-2 15-3 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 18-1 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 26-1 26-2 26-3 26-4 26-5 26-6 26-7 26-8 26-9 26-10 26-11 26-12 26-13 26-14 26-18 26-21 26-22 26-23 26-24 26-25 26-26 26-27 26-28 26-29 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 27-1 27-2 27-3 27-4 27-5 27-6 27-8 27-9 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 28-1 28-2 28-3 28-4 28-5 28-6 28-8 28-9 28-10 28-11 28-12 28-13 28-14 28-15 28-16 28-17 28-18 28-19 28-20 28-21 28-22 28-23 28-24 28-25 28-27 28-28 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 29-1 29-2 29-3 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 31-2 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 32-1 32-2 a compound of the formula wherein Ry has one of the meanings given in the following table: Compound Ry 34-1 34-3 34-4 34-6 a compound of the formula wherein Rx has one of the meanings given in the following table: Compound Rx 35-1 or a pharmaceutically acceptable salt thereof. 12. The compound of claim 1, wherein said compound is 2-[5-chloro-2-(2-methoxy-4-morpholin-4-yl -phenylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide, or N2-(4-[1,4′]Bipiperidinyl-1′-yl-2-methoxy-phenyl)-5-chloro-N4-[2-(propane-1-sulfonyl)-phenyl]-pyrimidine-2,4-diamine, or a pharmaceutically acceptable salt thereof. 13. A process for the production of a compound of formula I according to claim 1, comprising reacting a compound of formula II wherein R0, R1, R2, R3, R4, R5, and R6 are as defined in claim 1, and Y is a leaving group, with a compound of formula III wherein A, R7, R8, R9 and R10 are as defined in claim 1; and, if desired, converting a compound of formula I, wherein the substituents have the meaning as defined in claim 1, into another compound of formula I as defined in claim 1; and recovering the resulting compound of formula I in free from or as a salt, and, when required, converting the compound of formula I obtained in free form into the desired salt, or an obtained salt into the free form. 14. A pharmaceutical composition comprising a compound according to claim 1, as active ingredient together with one or more pharmaceutically acceptable diluents or carriers. 15. A combination comprising a therapeutically effective amount of a compound according to claim 1 and one or more known drug substances, said further drug substance being useful in the treatment of neoplastic diseases or immune system disorders. 16. A method for the treatment of breast tumors in a subject in need thereof which comprises administering an effective amount of a compound according to claim 1 or a pharmaceutical composition comprising same. 17. The method of claim 16, wherein said compound is 2-[5-chloro-2-(2-methoxy-4-morpholin-4-yl -phenylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide, or N2-(4-[1,4′]Bipiperidinyl-1′-yl-2-methoxy-phenyl)-5-chloro-N4-[2-(propane-1-sulfonyl)-phenyl]-pyrimidine-2,4-diamine, or a pharmaceutically acceptable salt thereof.