Compounds and compositions as protein kinase inhibitors

1. A compound of Formula I:

in which:

n is selected from 1 and 2;

Z is CH;

R 1 is —NHR 8 ; wherein R 8 is selected from hydrogen, C 1-6 alkyl, C 6-10 aryl-C 0-4 alkyl, pyridinyl, pyrazolyl, pyrazinyl, C 3-10 cycloalkyl-C 0-4 alkyl and morpholino-propyl; wherein any alkyl of R 8 is optionally substituted by a —NR 9 R 10 radical; wherein any aryl, pyridinyl, pyrazolyl, pyrazinyl, cycloalkyl or morpholino of R 8 is optionally substituted by one to three radicals selected from halo, hydroxy, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, trifluoromethyl, —XNR 9 R 10 , —XOXNR 9 R 10 , —XNR 9 S(O) 0-2 R 10 , —XC(O)NR 9 R 10 , —XNR 9 C(O)XOR 9 , —XNR 9 C(O)NR 9 R 10 , —XNR 9 XNR 9 R 10 , —XC(O)NR 9 XNR 9 R 10 , —XNR 9 XOR 9 , —XOR 9 , —XNR 9 C(═NR 9 )NR 9 R 10 , —XS(O) 0-2 R 11 , —XNR 9 C(O)R 9 , —XNR 9 C(O)XNR 9 R 10 , —XNR 9 C(O)R 11 , —XC(O)R 11 , —XR 11 , —XC(O)OR 10 and —XS(O) 0-2 NR 9 R 10 ; wherein X is a bond or C 1-4 alkylene; R 9 and R 10 are independently selected from hydrogen, C 1-6 alkyl and C 3-12 cycloalkyl; and R 11 is selected from piperazinyl, morpholino and pyrrolidinyl; wherein R 11 is optionally substituted with 1 to 3 radicals selected from C 1-6 alkyl, —XNR 9 R 10 , —XNR 9 XNR 9 R 9 , —XNR 9 XOR 9 and —XOR 9 ; wherein X, R 9 and R 10 are as described above;

R 2 and R 3 are hydrogen or R 2 and R 3 together form ═O;

R 4 is selected from hydrogen and C 1-6 alkyl;

R 5 is selected from C 1-6 alkyl and C 1-6 alkoxy;

R 6 is —NHC(O)R 13 ; wherein R 13 is selected from C 1-6 alkyl, C 6-10 aryl, C 3-10 cycloalkyl, pyrazolyl, pyridinyl; wherein any aryl, cycloalkyl, pyrazolyl or pyridinyl of R 13 is substituted by one to three radicals independently selected from halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6 alkyl, C 1-6 alkoxy, —XNR 9 R 9 , —XNR 9 XNR 9 R 9 , —XNR 9 C(O)R 9 , —XC(O)OR 9 , —XNR 9 S(O) 2 R 9 , —XNR 9 S(O)R 9 , —XNR 9 SR 9 and —XR 14 ; wherein X and R 9 are as defined above and R 14 is selected from imidazolyl, 1,3,4-triazinyl, morpholino, piperazinyl and pyrrolidinyl; wherein any imidazolyl, 1,3,4-triazinyl, morpholino, piperazinyl or pyrrolidinyl of R 14 is optionally substituted with a radical selected from C 1-6 alkyl, trifluoromethyl, —NR 9 R 9 and —C(O)OR 9 ; wherein R 9 is as described above.

2. The compound of claim 1 in which R 1 is —NHR 8 ; wherein R 8 is selected from diethyl-amino-propyl, phenyl, pyridinyl, morpholino-propyl, pyrazolyl, pyrazinyl, cyclopropyl; wherein said phenyl, pyridinyl, morpholino-propyl, pyrazolyl, pyrazinyl or cyclopropyl is optionally substituted with 1 to 3 radicals independently selected from dimethyl-amino, methyl and morpholino.

3. The compound of claim 2 in which R 6 is selected from —NHC(O)R 13 ; wherein R 13 is selected from phenyl optionally substituted with 1 to 2 trifluoromethyl radicals.

4. The compound of claim 3 in which R 2 and R 3 are both hydrogen and R 4 is selected from hydrogen, methyl, and ethyl.

5. The compound of claim 4 selected from:

N-{3-[7-(3-Diethylamino-propylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide;

N-{4-Methyl-3-[1-methyl-2-oxo-7-(pyridin-3-ylamino)-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-phenyl}-3-trifluoromethyl-benzamide;

N-{4-Methyl-3-[1-methyl-7-(6-methyl-pyridin-3-ylamino)-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-phenyl}-3-trifluoromethyl-benzamide;

N-{3-[7-(2,5-Dimethyl-2H-pyrazol-3-ylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide;

N-{4-Methyl-3-[1-methyl-2-oxo-7-(pyrazin-2-ylamino)-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-phenyl}-3-trifluoromethyl-benzamide;

N-{4-Methyl-3-[1-methyl-7-(3-morpholin-4-yl-propylamino)-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-phenyl}-3-trifluoromethyl-benzamide;

N-{3-[7-(3-Diethylamino-propylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide;

N-{3-[7-(4-Diethylamino-butylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide;

N-{3-[7-(4,6-Dimethyl-pyridin-3-ylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide;

N-{3-7-(2,6-Dimethyl-pyridin-3-ylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide; and

N-{3-[7-(2,6-Dimethyl-pyridin-4-ylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrido[4,3-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide.

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable excipient.