Amidopyrimidone derivatives

Abstract

Amidopyrimidone derivatives

Description

Case P36187 Amidopyrimidone derivatives Claims 1. A compound formula I or II: 1 O wherein x1is either N or CH•, X3is either N or CR3, the dotted line represents a single bond when R5is oxo or a double bond when R5is NH2, R1is (Cl-C6)alkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents Rla, (Cl-C6)alkoxy optionally substituted with one or more, particularly one to three, more particularly one or two substituents Rib, halo(C1C6)alkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents Riaoptionally substituted with one or more, particularly one to three, more particularly one or two substituents Rib, (C3- C8)cycloalkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents Ric, heteroaryl optionally substituted with one or more, particularly one to three, more particularly one or two substituents Ridheterocycloalkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents Rieor phenyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents Rif Riaand Ribare each independently selected from (C3-C6)cycloalkyl, hydroxyl, heteroaryl, heterocycloalkyl and phenyl, wherein heteroaryl, heterocycloalkyl or phenyl are optionally substituted with one or more, particularly one to three, more particularly one or two substituents Rig• Ric, Rid, Rieand Rifare each independently selected from halogen, oxo, cyano, hydroxyl, (Cl-C6)alkyl, (Cl-C6)alkoxy, (C3-C6)cycloalkyl,halo(C1- C6)alkyl, halo(C1-C6)alkoxy, hydroxy(C1-C6)alkyl,heteroaryl, heterocycloalkyl and phenyl; Rigare each independently selected from halogen, cyano, hydroxyl, (Cl-C6)alkyl, (Cl-C6)alkoxy, (C3-C6)cycloalkyl,halo(C1-C6)alkoxy, hydroxy(C1-C6)alkyl R2is hydrogen, halogen, amino, (Cl-C6)alkyl, (Cl-C6)alkoxy,halo(C1-C6)alkoxy, (C3-C6)cycloalkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R2a,optionally substituted with one or more, particularly one to three, more particularly one or two substituents R2b,optionally substituted with one or more, particularly one to three, more particularly one or two substituents R2cheterocycloalkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R2dNR2fR2gor phenyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R2e R2aR2bR2cR2dand R2eare each independently selected from halogen, (Cl-C6)alkyl, (C1-C6)alkoxy,and halo(C1-C6)alkoxy; R2fand R2gare each independently selected from hydrogen or (Cl-C6)alkyl; R3is hydrogen, halogen, cyano, amino, (Cl-C6)alkyl, (Cl-C6)alkoxy, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C3-C6)cycloalkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R3a, (C3-C6)cycloalkyl-(C1-C6)alkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R3b, (C3-C6)cycloalkyl-(C1-C6)alkoxy optionally substituted with one or more, particularly one to three, more particularly one or two substituents R3cheterocycloalkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R3dor phenyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R3e R3a, R3bR3cR3dand R3eare each independently selected from halogen, (Cl-C6)alkyl, (Cl-C6)alkoxy, halo(C1-C6)alkyl and halo(C1-C6)alkoxy; R4is hydrogen, cyano, hydroxy, halogen, amino, (Cl-C6)alkyl, (Cl-C6)alkoxy, halo(C1-C6)alkyl, halo(C1-C6)alkoxy,(C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R4a, (C3optionally substituted with one or more, particularly one to three, more particularly one or two substituents R4b,optionally substituted with one or more, particularly one to three, more particularly one or two substituents R4cheterocycloalkyl optionally substituted with one or more, particularly one to three, more particularly one or two substituents R4d, -C02R4aor CONR 4b R4c. R4aR4bR4cand R4dR4eare each independently selected from hydrogen and (Cl-C6)alkyl; R5is -NH2; and pharmaceutically acceptable salts thereof. 2. The compound according to claim l, wherein the compound is of formula I. 1 RO R NH2 wherein Xl, X3RI, R2and R4are as defined according to claim 1. 3. The compound according to any one of claims 1 to 2, wherein X3is CR3and Xlis N. 4. The compound according to any one of claims 1 to 3, wherein R1is oxaspiro[2.5]octanyl 5or tetrahydropyranyl optionally substituted with one (Cl-C3)alkyl. 5. The compound according to any one of claims 1 to 4, wherein R1is tetrahydrofuranyl substituted with one Riesubstituted in alpha, tetrahydropyranyl substituted with one Riesubstituted in alpha, oxaspiro[2.5]octanyl or 2, 3-dihydrobenzofuranyl substituted with one Rle. 6. The compound according to any one of claims 1 to 5, wherein wherein Ridare each independently selected from cyano, chloro and methyl. 7. The compound according to any one of claims 1 to 6, wherein R1is 2,3dihydrobenzofuranyl, oxaspiro[2.5]octanyl, 3-methyl-phenyl, 2-methyl-phenyl, 2methylbenzonitrile, 2-chlorophenyl, phenyl, 2-methylpyridin-3-yl, 4-methylpyridin-3-yl, 4 2-chloropyridin-3-yl or 4-methylpyrimidin-5-yl 8. The compound according to any one of claims 1 to 7, wherein R2isor cyclopropyl optionally substituted by halogen or (Cl-C3)alkyl, 9.The compound according to any one of claims 1 to 8, wherein R2is trifluoromethyl, difluoromethoxy, trifluoromethoxy or cyclopropyl. 10. The compound according to any one of claims 1 to 9, wherein R3is hydrogen, halogen or cyano. 11 . The compound according to any one of claims 1 to 10, wherein R3is hydrogen. 12. The compound according to any one of claims 1 to 11, wherein R4is hydrogen. 13. The compound according to any one of claims 1 to 12, selected from the group consisting of: 4-amino-7-cyclopropyl - 1 -(0-tol yl)pyr1 do [2,3 -d] pyr1m1d1n-2( 1 H)-one 4-amino-7-cyclopropyl - 1 -(2-methoxyphenyl)pyr11 H)-one 4-amino-7-(teft-butyl)- 1 -(0-tolyl)pyr1 do [2,3 -d] pyr1m1 4-amino-1-(2-methoxyphenyl)-7-phenylpyr1do[2,3-d]pyr1m1d1n-2(1H)-one 4-amino-7-(3 , 3 -d1fluoroazet1 d1n- 1 -yl)- 1 -(0-tol yl)pyr11 H)-one 4-amino-7-cyclopropyl - 1 -(tetrahydrofuran-3 -yl)pyr1 do[2, 3-d]pyr1m1d1n-2( 1 H)-one 4-amino-7-cyclopropyl - 1 -(2-m ethylpyr1 d1n-3 -yl)pyr11 H)-one 4-amino-7-cyclopropyl - 1 -(2-oxop1per1 d1n-4-yl)pyr11 H)-one 4-amino-7-cyclopropyl- 1 -((c1 s)-2-methyltetrahydrofuran-3-d]pyr1m1 d1n-2( 1 H)one 4-amino-7-cyclopropyl - 1 -(0-tol yl)pyr1 do [4,3 -d] pyr1m1d1n-2( 1 H)-one 4-amino-7-cyclopropyl - 1 -(2-methylpyr1 d1n-3 -yl)qu1nazol1n-2-one 4-amino-7-cyclopropyl - 1 -(2-methylphenyl)qu1nazol1n-2-one 7-cyclopropyl-l-(2-methylphenyl)qu1nazol1ne-2,4-d1one 4-amino-7-cyclopropyl- 1 -(0-tol yl)pyr1m1 do [4,5 -d] pyr1m1d1n-2( 1 H)-one 7-cyclopropyl-l-(2-methylpyr1d1n-34-amino-7-cyclopropyl- 1 -(2-m ethoxypyr1 d1n-3 -yl)pyr14-amino-7-cyclopropyl -6 -fluoro- 1 - (2 -methylpyr1 d1n-3 7-cyclopropyl- 1 -(2-methylphenyl)pyr1 do [2,3 -d] pyr1m1d1ne-2,4-d1 one 3-(4-amino-7-cycl-d] pyr1m1 d1n- 1 (2H)-yl)p1col1non1tr1le 4-amino-7-cyclopropyl - 1 -(oxan-3 -yl)pyr1 do[2, 3-d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 -[ 1 -(oxol an-3do[2,3-d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 -(3-fluoro-2-methoxyphenyl)pyr1do[2,3 -d]pyr1m1 d1n-2( 1 H)-one 4-amino-7-cyclopropyl- 1 -(2,3 -d1hydrob enzofuran-4-yl)pyr1-d]pyr1m1 d1n-2( 1 H) -one 4-amino-6-chloro-7-cycl opropyl- 1 -(2-m ethylpyr1-d]pyr1m1 d1n-2( 1 H) -one 3-(4-amino-7-cycl opropyl-2-oxopyr1 do [2,3 -d] pyr1m1 d1n- 1enzon1tr1le -d] pyr1m1 d1n- 1enzon1tr1le 4-amino-7-cyclopropyl - 1 -( 13-d]pyr1m1d1n-2( 1 H)-one 4-amino- 1 -(2-methylpyr1d1n-3 -yl)-7-(oxetan-3 -yl)qu1nazol1n-2(lH)-one 7-cyclopropyl- 1 -(2-methylpyr1 d1n-3-d] pyr1m1d1ne-2,4-d1 one 4-amino-7-cyclop entyl- 1 -(2-methyl -3 -pyr1 dyl)pyr1 do[2,3-d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 1 SR,2RS)-2-hydroxycyclopentyl)pyr1do[2,3 -d]pyr1m1 d1n-2( 1 H)-one 4-amino-2-cyclopentyl-7-(o-tolyl)pyrazolo[3,4-d]pyr1m1d1n-6-one; form1c ac1d 4-amino-7-cyclop entyl- 1 -(4-methylpyr1m1 d1n-5 -yl 4-amino-7-cyclopropyl- 1 -(3 -fluoro-2-mH)-one 4-amino-7-cyclopropyl-l -[(3R)-oxan-3-d] pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 - [(3 S)-oxan-3 -yl]pyr1 do 4-amino-7-cyclopropyl - 1 -(4-m ethyltetrahydrofuran -3 -yl)pyr1 -d]pyr1m1 d1n-2( 1 H) -one 4-amino-7-cyclopropyl -2 -ox o- 1 -(0-tolyl)- 1oxam1de 4-amino-7-[(l S,4R)-3 -azab1 cycl 0[2.2. 1 ]heptan-3 -yl]- 1 -(2-methylpyrazol-3 -yl)pyr1 do[2, 3 d]pyr1m1d1n-2-one; form1c ac1d 4-amino-1-(2-m ethyl pyr1 d1n-3ethyl) qu1nazol1n-2-one 4-amino-7-cyclopropyl - 1 - [rac-(2R, 3 S)-2-methyl oxol an-3-yl]pyr1do[2,3 -d]pyr1m1 d1n-2 -one 4-amino-7-cyclobutyl-l -(2-methyl-3-pyr1dyl)pyr1do[2,3-d]pyr1m1d1n-2-one; form1c ac1d 4-amino-7-cyclopropyl oxy- 1 -(2-methylpyr1 d1n-3 -yl)qu1nazol1n-2-one 4-amino- 1 -(2-methylpyr1 d1n-3 -yl)-7-(tr1fluoromethyl)pyr1do[2,3-d]pyr1m1d1n-2(lH)-one 4-amino-7-(7-azab1cycl o [2.2. 1 ] heptan-7-yl)- 1-d] pyr1m1 d1n-2- one; form1c ac1d 4-amino-7-cyclopropyl - 1 -(3 -hydroxycycl opentyl)pyr1 do[2,3 -d]pyr1m1d1n-2( 1 H)-one 4-amino-7-(d1fluorom ethoxy)- 1 -(2-methylpyr1 d1n-31 H)-one 4-amino-7-(d1fluorom ethyl)- 1 -(2-methylpyr1 d1n-3 -yl)qu1nazol1n-2( 1 H)-one 4-amino-7-[(lR,2S)-2-fluorocyclopropyl]-l -(2-methyl-3 -pyr1dyl)pyr1do[2,3-d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl-l -(2-methylpyr1 d1n-3 -yl)-2-oxo--d] pyr1m1 d1ne-6-carbon1tr1le3-(4-amino-7-1sopropyl 4-amino-7-cyclopropyl -2 -ox o- 1 -(0-tolyl)- 1on1tr1le 4-amino-7-methoxy- 1 - (2 -m ethyl pyr1 d1n-3 -yl)qu1nazol1n-2(lH)-one 4-amino- 1 -(2-methylpyr1 d1n-31 H)-one 4-amino-7-(4, 5-d1hydrofuran-3 -yl)- 1 -(2 -m ethylpyr11 H) -one 4-amino- 1 -(2-m ethylpyr1 d1n-3H) -one 4-amino-7-cyclopropyl - 1 -(2-methylpyr1 d1n-3 -yl)pyr1 do[2,3-d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 -(2-methylpyr1 d1n-3 -yl)pyr1 do[2,3-d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 -(4-m ethylth1 azol -5 -yl )pyr1 4-amino-7-cyclopropyl-l -(4-methylpyr1m1d1n-5-yl)pyr1do[2,3-d]pyr1m1d1n-2(lH)-one 4-amino-7-cyclopropyl- 1 -(2-(tr1fluorom ethyl )pyr1-d]pyr1m1 d1n-2( 1 H) -one 4-amino-7-cyclopropyl-l -(2-methylpyrazol-3-d] pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 -(2,3 -d1hydrob1 H)-one (R)-4-amino- 1 -(tetrahydro-2H-pyran-31 H)-one 4-amino-7-cyclopropyl - 1 -(4-methylpyr1 d1n-3 -yl)pyr1 do[2,3-d]pyr1m1d1n-2( 1 H)-one 4-amino-7-ethyl-l -(2-methylpyr1d1n-3 4-amino-7-[(l S,2R)-2-fl uorocycl opropyl] - 1 - [(3 R)-tetrahydropyran-3 -yl]pyrl do [2,3 d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl- 1 -(4-m ethyl ox 3-(4-amino-6-chl oro-7-1 sopropyl -2 -oxopyr1 do [2,3 -d] pyr1m1d1n- 1 (2H)-yl)-2methoxybenzon1tr1le 4-amino-7-cyclopropyl - 1 -((R)- 1 -((S)-tetrahydrofuran-3-yl)ethyl)pyr1do[2,3 -d]pyr1m1 d1n-2( 1 H)one 4-amino-7-cyclopropyl - 1 -((R)- 1 -((R)-tetrahydrofuran-3-yl)ethyl)pyr1do[2,3 -d]pyr1m1 d1n-2( 1 H)one 4-amino-7-(2-fluoropropan-2-yl)- 1 -(2-m ethyl pyr1 d1n-3 -yl)qu1nazol1n-2-one 4-amino-5 -methoxy- 1 - (2 -methyl pyr1 d1n-3 -yl)-7-(tr1fluoromethyl)qu1nazol1n-2(lH)-one 4-amino-7-cyclopropyl - 1 -(4-fluoro-2-methoxypyr1 d1n-3-yl)pyr1do[2,3 -d]pyr1m1 d1n-2( 1 H)-one 4-amino-5-fluoro- 1 -(2-methylpyr1 d1n-3 -yl)-7-(tr1fluoromethyl)qu1nazol1n-2(1H)-one 4-amino-7-cyclopropyl - 1 -( 1 -ethyl- 1 H-pyrazol -5-yl)pyr1do[2,3-d]pyr1m1d1n-2( 1 H)-one 4-amino-7-chloro-l 4-amino-7-cyclopropyl-l -(2,31 H) -one -d] pyr1m1d1n-2one 4-amino-7-cyclopropyl - 1 -[( 1 R)- 1 - [(3 S)-oxol an-3 -yl] ethyl]pyr1do[2,3 -d]pyr1m1 d1n-2-one 4-amino-7-cyclopropyl - 1 - [( 1 R)- 1 - [(3R)-oxol an-3 -yl] ethyl]pyr1do[2,3-d]pyr1m1d1n-2-one 3-(4-amino-6-chl oro-7-cycl opropyl -2-oxopyr1 do [2,3 -d]pyr1m1d1n- 1 (2H)-yl)-2methoxybenzon1tr1le 4-amino-7-cyclopropyl- 1 -(4-oxasp1ro[2.5] 4-amino-6-chloro-7-cycl opropyl- 1 -(2-m ethoxypyr1 d1n-3-d]pyr1m1 d1n-2( 1 H) -one 4-amino-7-cyclopropyl - 1 -(4-fluoro-2-m ethyl phenyl)pyr1-d]pyr1m1 d1n-2-one 4-amino-7-cyclopropyl - 1 -(3 -ethylphenyl)pyr1 do [2, 31 H)-one 4-amino-7-cyclopropyl-l -(m-tolyl)pyr1 do [2,3 -d] 4-amino-7-cyclopropyl - 1 -(3 , 5 -d1fluorophenyl)pyr11 H)-one 4-amino-7-cyclopropyl-l -(6-methoxypyr1d1n-2-yl)pyr1do[2,3-d]pyr1m1d1n-2(lH)-one 4-amino-7-cyclopropyl- 1 -(3 -methoxyphenyl)pyr1 -d] pyr1m1d1n-2( 1 H)-one 4-amino-7-cyclopropyl - 1 -(2,3 -d1fluorophenyl)pyr11 H)-one 4-amino-7-cyclopropyl-l 4-amino-7-cyclopropyl - 1 -( 1 -(oxazol -5 -yl)ethyl)pyr1 do[2,3-d]pyr1m1d1n-2( 1 H)-one 3-(4-amino-2-oxo-7-(tr1fluoromethyl)qu1nazol1n-l (2H)-yl)-2-methylbenzon1tr1le-8--d] pyr1m1d1n-l (2H)-yl)-2-methylbenzon1tr1le 4-amino-7-cyclopropyl-l -(2,6-d1fluorophenyl)pyr1do[2,3-d]pyr1m1d1n-2(lH)-one 4-amino-7-cyclopropyl- 1 -(2-fluorophenyl)pyr1 do [2,3 -d] 4-amino-7-cyclopropyl - 1 -(3 -fluorophenyl)pyr1 do [2,3 -d] pyr1m1d1n-2( 1 H)-one 4-amino-7-cyclopropyl - 1 -[ 1 -(oxetan-3 -yl)ethyl]pyr1 do[2,3-d]pyr1m1d1n-2-one 4-amino-7-(d1fluorom ethoxy)- 1 -(2-m ethyl ph enyl-d]pyr1m1 d1n-2 -one 4-amino-7-cyclopropyl - 1 -( 1 -pyr1 d1n-2-yl ethyl)pyr1do[2,3-d]pyr1m1d1n-2-one 4-am1 no- 1 -(2-methyl -3 -pyr1 dyl)- 7-(2 , -tr1fluoroethyl)qu1nazol1 n-2-one hydrochl or1 de 4-amino-7-cyclopropyl- 1 -(tetrahydro-2H-pyran-4-yl)pyr1 -d]pyr1m1 d1n-2( 1 H) -one 4-amino- 1 -(2-chl oropyr1d1n-3 -yl)-7-cyclopropylpyr1do[2,3-d]pyr1m1d1n-2(lH)-one 4-amino-2-cyclop entyl -7-(2-methyl-3 -pyr1 dyl)pyrazol ,4-d]pyr1m1d1n-6-one 4-amino-5-chloro- 1 -(2 -m ethyl pyr1 d1n-31 H)-one 4-amino-l 4-amino-7-cyclopropyl- 1 -( 1 H-1ndol -4-yl)pyr1 do [2,3 -d] pyr1m1d1n-2-one 4-amino-7-cyclopropyl-l -[6-(tr1fluoromethoxy)pyr1d1n-2-yl]pyr1do[2,3-d]pyr1m1d1n-2-one -one H) -d] pyr1m1 d1n- 1 (2H)-yl)benzon1tr1le 4-amino-7-(d1fluorom ethoxy)- 1 -(4-oxasp1ro[2.5 ] octan-8-yl)qu1nazol1n-2( 1 H)-one 4-amino-7-(d1fluorom ethoxy)- 1 -(0-tolyl)qu1nazol1n-2( 1 H)-one 3-(4-amino-7-cycl -d] pyr1m1d1n- 1 enzon1tr1le 4-amino-7-cyclopropyl - 1 - [(8 S)-4-oxasp1ro[2.5] -d]pyr1m1 d1n-2-one 4-amino-7-cyclopropyl - 1 -[(8R)-4-oxasp1ro[2.5] -d]pyr1m1 d1n-2-one 4-amino-l 4-amino-7-cyclopropyl - 1 -(1H-1ndazol -4-yl)pyr1 do 1 H)-one 4-amino-7-cyclopropyl - 1 -(2,3 -d1methylphenyl)pyr1 1 H)-one 4-amino-l -(2-chloropyr1d1n-3 4-amino- 1 -(2-chloropyr1d1n-3 H)-one 4-amino- 1 -(2-chl oropyr1d1n-3 -yl)-7-cyclopropylpyr1do[2,3-d]pyr1m1d1n-2(lH)-one 4-amino-7-(d1fluorom ethoxy)- 1 -(m -tol 4-amino-7-(d1fluorom ethoxy)- 1 -(2-fluoro-3 -methylphenyl)qu1nazol1n-2( 1 H)-one 4-amino-7-cycl opropyl - 1 -(2 -(tr1fluorom ethyl-d]pyr1m1 d1 n-2( 1 H)-one 4-amino-7-cyclopropyl - 1 -(3 -(fluorom ethyl)-2-m-d]pyr1m1 d1n-2( 1 H) -one 4-amino- 1 -(2-chl oro-3 -m ethyl phenyl)-7-cycl opropyl-d]pyr1m1d1n-2-one 4-amino- 1 -(3 -chl oro-2 -m ethyl phenyl) -7 -cycl opropylpyr1do[2,3-d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 -(2,3 -d1 chl orophenyl )pyr1 4-amino-7-cyclopropyl- 1 -(2-fl uoro-3 -m ethyl 3-(4-amino-7-cyclopropyl-2-oxopyr1 do [2,3 -d] pyr1m1 d1n- 1 (2H)-yl)-2-fluorobenzon1tr1le (S)-4-amino-7-cyclopropyl - 1 -(oxepan-3 -yl)pyr1 do 1 H)-one (R)-4-amino-7 -cycl opropyl - 1 -(oxepan-3 -yl)pyr1 do 1 H)-one 4-amino-7-cyclopropyl - 1 -(3-hydroxy-2-methylphenyl)pyr1do[2,3 -d]pyr1m1 d1n-2( 1 H)-one 4-amino-7-(d1fluorom ethoxy)- 1 -(31 H)-one 4-amino-7-cyclopropyl- 1 - [rac-(2 S, 3 S)-2-methyltetrahydropyran-3 -yl ]pyr1 -d] pyr1m1 d1n-2one 4-amino- 1 -(bH)-one 4-amino-7-cycl opropyl- 1 S, 3 R) -2 -m ethyltetrahydro-2H-pyran-3 -yl)pyr1 do [2,3 -d] pyr1m1 d1n- 4-am1 no-7-cycl opropyl - 1 -((2R, 3 S) -2 -m ethyltetrahydro-2H-pyran-3 -yl)pyr1 do [2,3 -d] pyr1m1 d1n- (-)-4-amino- 1 -(2-chloro-3 -fluorophenyl)-7-cycl (+)-4-amino- 1 -(2-chl oro-3 -fluorophenyl)-7-cycl (-)-4-amino- 1 -(2-chlorophenyl)-7-cycl opropylpyr1 (+)-4-amino- 1 -(2-chl orophenyl)-7-cycl opropylpyr1 4-amino-7-cyclopropyl -6 -(d1fluorom ethoxy)- 1 -(0-tolyl)pyr1 4-amino-7-cyclopropyl- 1 -(6, 7 -d1hydro- 5H-pyrrolo[ 1 2-one;form1c ac1d 4-(2-chlorophenyl)-6-cycl opropyl- 1 -1m1no-pyr1 4-amino-7-cyclopropyl-l - [2- (tr1 fluorom 4-amino-1-(2-chl oro-3 -pyr1 4-amino-7-cyclopropyl- 1 4-amino-7-cyclopropyl - 1 -( 1 ,4-d1 oxepan-6-yl)pyr1 do[2,3-d]pyr1m1d1n-2-one 4-amino-7-cyclopropyl - 1 -(3 -fluoro-2-methylphenyl)qu1nazol1n-2-one 14. The compound according to any one of claims 1 to 12, selected from the group consisting of: 4-amino-7-cyclopropyl - 1 -(0-tol yl)pyr1 do [2,3 -d] pyr1m1d1n-2( 1 H)-one 4-amino-7-cyclopropyl - 1 -(2-methylpyr1 d1n-3 -yl)pyr1 do[2,3-d]pyr1m1d1n-2( 1 H)-one- 10 - -d] pyr1m1d1n- 1 4-amino-7-cyclopropyl - 1 -(2,3 -d1hydrobenzofuran-4-yl)pyr1 -d]pyr1m1 d1n-2( 1 H)-one 4-amino-7-cyclopropyl- 1 -(3 -fluoro-2-methylphenyl1 H)-one 4-amino-7-cyclopropyl - 1 -(oxan-3 -yl)pyr1 do [2, 3-d]pyr1m1d1n-2-one 4-amino-7-(d1fluorom ethoxy)- 1 -(2-methylpyr1 d1n-31 H)-one 4-amino- 1 -(2-m ethyl pyr1 d1n-31 H)-one 4-amino-7-cyclopropyl - 1 -(2,3 -d1hydrob1 H)-one 4-amino-7-cyclopropyl - 1 -(2,3 -d1hydrob enzofuran-7-yl)pyr11 H) -one 4-amino- 1 -(2-chlorophenyl)-7-cycl 4-amino-7-cyclopropyl- 1 -(4-oxasp1ro[2.5] 4-amino- 1 -(2-chl oropyr1d1n-3 -yl)-7-cyclopropylpyr1do[2,3-d]pyr1m1d1n-2(lH)-one 4-amino-7-(d1fluorom ethoxy)- 1 -(2-m ethyl ph enyl-d]pyr1m1 d1n-2-one -d] pyr1m1d1n- 1 (2H)-yl)-2-methylbenzon1tr1le 4-amino-7-cyclopropyl-l4-amino-7-cyclopropyl - 1 -[(8-d]pyr1m1 d1n-2-one 4-amino-7-cyclopropyl-l (R)-4-amino-7-cycl opropyl - 1 -(oxepan-3 -yl)pyr1 do [2,3 -d] pyr1m1d1n-2( 1 H)-one 4-amino-7-cycl opropyl - 1 S, 3 R) -2 -m ethyltetrahydro-2H-pyran-3 -yl)pyr1 do [2,3 -d] pyr1m1 d1n-2( 1 H)one 15. A compound according to any one of claims 1 to 14 for use as a therapeutically active substance. 16. Compounds of formula I or II according to any one of claims 1 to 14 or their pharmaceutically acceptable salts for the use in the treatment, prevention and / or delay of 5 progression of Lung Aenocarcinoma, Melanoma, Pancreatic Adenocarcinoma, Head and Neck Squamous Cell Carcinoma, Lung Squamous Cell Carcinoma, Esophageal, Carcinoma, Glioblastmoa Multiforme, and Mesothelioma.

Claims

Amidopyrimdone derivatives Claims 1.Compound formula I or II: wherein X1 is either N or CH•, X3 is either N or CR3, the dotted line represents a single bond when R5 is Oxo or a double bond when R5 is NH2, R1 is an alkyl (Cl-C6) optionally substituted with one or more, especially one to three, further substituents. In particular one or two substituents R1a, (Cl-C6) alkoxy optionally with one or more substituents, in particular one to three, in particular one or two substituents R1a, halo (C1-C6) alkyl optionally with one or more substituents, in particular one to three, in particular one or two substituents R1a optionally with one or more substituents, in particular one to three, in particular one or two substituents R1a, (C3-C8) cycloalkyl optionally with one or more substituents, in particular one to three, in particular one or two substituents R1a, heteroaryl optionally with one or more substituents, in particular one to three, in particular one or two substituents R1a, heterocycloalkyl optionally with one or more substituents, in particular one to three, more particularly one or two substituents R1a or phenyl optionally with one or more substituents, in particular one to three, in particular one or two substituents R1a,Specifically one or two substituents Rif, Ria and Rib are each independently selected from halogen, oxo, cyano, hydroxyl, (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, halo(C1-C6))alkyl, halo(C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkyl, heteroaryl, heterocycloalkyl and phenyl; Rig is each independently selected from halogen, cyano, hydroxyl, (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, hydroxy(C1-C6)alkyl and (C1-C6)alkoxy-(C1-C6)alkyl; R2 is hydrogen, halogen, amino, (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C3-C6)cycloalkyl optionally substituted with one or more, especially one to three, especially one or two substituents R2a, (C3-C6)cycloalkyl-(C1-C6)alkyl optionally substituted with one or more, especially one to three, especially one or two substituents R2b, (C3-C6)cycloalkyl-(C1-C6)alkoxy optionally substituted with one or more, especially one tothree, in particular one or two R2C substituents, heterocycloalkyl optionally with one or more substituents, in particular one to three, in particular one or two R2d substituents NR2fR2g or phenyl optionally with one or more substituents, in particular one to three, in particular one or two R2e substituents R2a, R2b, R2c, R2d and R2e are each independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkyl and halo(C1-C6)alkoxy. R2f and R2g are each independently selected from hydrogen or (C1-C6)alkyl. R3 is hydrogen, halogen, cyano, amino, (C1-C6) alkyl, (C1-C6) alkoxy, halo(C1-C6) alkyl, halo(C1-C6) alkoxy, (C3-C6) cycloalkyl. Optionally with one or more substituents, especially one to three, especially one or two substituents R3a, (C3-C6) cycloalkyl-(C1-C6) alkyl optionally with one or more substituents, especially one to three, especially one or two substituents R3b C3-C6)) cycloalkyl-(C1-C6) alkoxy optionally with one or more substituents, especially one to three, especially one or two substituents Rc3 heterocycloalkyl optionally with one or more substituents, especially one to three, especially one or two substituentsR3d or phenyl is optionally substituted with one or more, especially one to three, especially one or two R3e substituents. R3a, R3b, R3c, R3d and R3e are each independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkyl and halo(C1-C6)alkoxy. R4 hydrogen, cyano, hydroxy, halogen, amino, (C1-C6) alkyl, (C1-C6) alkoxy, halo(C1-C6) alkyl, halo(C1-C6) alkoxy, (C1-C6) alkoxy(C1-C6) alkyl, (C3-C6) cycloalkyl, (C6-C3) cycloalkyl-(C1-C6) alkyl, (C3-C6) cycloalkyl optionally with one or more substituents, in particular one to three, in particular one or two substituents R4a, (C3-C6) cycloalkyl-(C1-C6) alkyl optionally with one or more substituents, in particular one to three, in particular one or two substituents R4b, (C3-C6) cycloalkyl-(C1-C6) alkoxy optionally with one or more substituents, in particular one to three, in particular one or two substituents R4C, heterocycloalkyl optionally substituted with one or more, especially one to three, especially one or two R4d, -C02R4a or -CONR4bR4c substituents. R4a, R4b, R4c and R4d, R4e are each independently selected from hydrogen and (C1-C6)alkyl.R5 is -NH2. and pharmaceutically acceptable salts thereof.

2. The compound of claim 1, wherein the compound of formula I is as follows: 1 ROR NH2 wherein X1, X3R1, R2 and R4 are as defined in claim 1.

3. The compound according to any one of claims 1 to 2, wherein X3 is CR3 and X1 is N.

4. The compound according to any one of claims 1 to 3, wherein R1 is oxaspiro[2.5]octanyl 5 or tetrahydropyranyl optionally substituted with a (Cl-C3)alkyl.

5. The compound according to any one of claims 1 to 4, wherein R1 is tetrahydrofuranyl substituted with a R1 in the alpha position, tetrahydropyranyl substituted with a R1 substituted in the alpha position, oxaspiro[2.5]octanyl or 2,3-dihydrobenzofuranyl substituted with a R1 substituted.

6. The compound according to any one of claims 1 to 5, wherein R 1 and R 2 are each independently selected from cyano, chloro and methyl.

7. The compound according to any one of claims 1 to 6, wherein R1 is 2,3-dihydrobenzofuranyl, oxaspiro[2.5]octanyl, 3-methyl-phenyl, 2-methyl-phenyl, 2-methylbenzonitrile, 2-chlorophenyl, phenyl, 2-methylpyridin-3-yl, 4-methylpyridin-3-yl, 4-chloropyridin-3-yl or 4-methylpyrimidin-5-yl.

8. The compound according to any one of claims 1 to 7, wherein R2 is (halo(C1-C3)alkyl, halo(C1-C3)alkoxy or cyclopropyl) optionally substituted with halogen or (C1-C3)alkyl.

9. A compound according to any one of claims 1 to 8, wherein R2 is trifluoromethyl, difluoromethoxy, trifluoromethoxy or cyclopropyl.

10. A compound according to any one of claims 1 to 9, wherein R3 is hydrogen, halogen or cyano.

11. A compound according to any one of claims 1 to 10 wherein R3 is hydrogen.

12. A compound according to any one of claims 1 to 11 wherein R4 is hydrogen.

13. The composition according to any one of claims 1 to 12, selected from the group consisting of: 4-amino-7-cyclopropyl-1-(o-tolyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino- 7-cyclopropyl-l -(2-methoxyphenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino- 7-(tert-butyl )-1-(o-tolyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-1-(2-methoxyphenyl )-7-phenylpyrido[2,3-d]pyrimidin-2(lH)-one 4-amino- 7-(3,3-difluoroazetidin-l -yl)-l -(o-tolyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(tetrahydrofuran-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(2-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(2-oxopiperidin-4-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-1-((cis)-2-methyltetrahydrofuran-3-yl)pyrido[2,3-d]pyrimidin-2(1H)- one 4-amino-7-cyclopropyl-l -(o-tolyl)pyrido[ 4,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-1-(2-methylpyridin-3-yl)quinazolin-2-one 4-amino-7-cyclopropyl-1-(2-methyl phenyl)quinazolin-2-one 7-cyclopropyl-1-(2-methylphenyl)quinazoline-2,4-dione 4-amino-7-cyclopropyl-l -(o-tolyl)pyrimido[ 4,5-d]pyrimidin-2(1H)-one 7-cyclopropyl-1-(2-methylpyridin-3-yl)quinazoline-2,4-dione 4-amino-7-cyclopropyl-1-(2-methoxypyridin-3-yl )pyrido[2,3-d]pyrimidin-2(lH)-one 4-amino-7-cyclopropyl-6-fluoro-l -(2-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 7-cyclopropyl-1-(2-methyl phenyl)pyrido[2,3-d]pyrimidine-2,4-dione 3- ( 4-amino - 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H) -yl ) picolinonitrile 4-amino - 7-cyclopropyl-1- ( oxan-3-yl ) pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-[ 1-( oxolan-3-yl)ethyl]pyrido[2,3-d]pyrimidin-2-one 4- amino - 7-cyclopropyl- l -( 3-fluoro-2-methoxyphenyl ) pyrido[2,3-d]pyrimidin-2 ( lH ) -one 3- ( 4-amino - 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H) -yl ) -2-methylbenzonitrile 4-amino-1- ( 2-methyl pyridin-3-yl ) - 7-propan-2-yl pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-(2,3-dihydrobenzofuran-4-yl )pyrido[2,3-d]pyrimidin-2(lH)-one 4- amino-6-chloro-7-cyclopropyl-l -( 2-methylpyridin-3-yl ) pyrido[2,3-d]pyrimidin-2 (1H) -one 3- ( 4-amino - 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H) -yl ) -2-methoxybenzonitrile 3- ( 4-amino - 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H) -yl ) -2-ethoxybenzonitrile 4-amino-7-cyclopropyl-l -(l -(tetrahydrofuran-2-yl)ethyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-1-(2-methylpyridin-3-yl)- 7-(oxetan-3-yl )quinazolin-2(1H)-one 7-cyclopropyl-1-(2-methyl pyridin-3-yl )pyrido[2,3-d]pyrimidine-2, 4-dione 4-amino-7-((1RS,2RS)-2-methylcyclopropyl)- l -(2-methyl pyridin-3-yl )pyrido[2,3-d]pyrimidin- 2( 1H)-one 4-amino-7-cyclopentyl-l -(2-methyl-3-pyridyl)pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-( (1 SR,2RS)-2-hydroxycyclopentyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-2-cyclopentyl- 7-(o-tolyl)pyrazolo[3,4-d]pyrimidin-6-one; formic acid 4-amino-7-cyclopentyl-1-(4-methylpyrimidin-5-yl )pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-(3-fluoro-2-methyl phenyl )pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-7-cyclopropyl-1-[ (3R)-oxan-3-yl]pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-[ (3S)-oxan-3-yl]pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -(4-methyltetrahydrofuran-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-2-oxo-l -(o-tolyl)-l ,2-dihydropyrido[2,3-d]pyrimidine-5-carboxamide 4-amino-1-(2-methoxy-3-pyridyl )-7-tetrahydropyran-2-yl-pyrido[2,3-d]pyrimidin-2-one 4-amino-7-[ (1 S,4R)-3-azabicyclo[2.

2. l ]heptan-3-yl ]-l -(2-methylpyrazol-3-yl)pyrido[2,3- d]pyrimidin-2-one; formic acid 4-amino-1-(2-methylpyridin-3-yl)- 7-(trifluoromethyl)quinazolin-2-one 4-amino-7-cyclopropyl-1-[ rac-(2R,3 S)-2-methyloxolan-3-yl ]pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclobutyl-l -(2-methyl-3-pyridyl)pyrido[2,3-d]pyrimidin-2-one; formic acid 4-amino-7-cyclopropyloxy-1-(2-methylpyridin-3-yl)quinazolin-2-one 4-amino-1-(2-methyl pyridin-3-yl )-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-2(IH)-one 4- amino - 7-( 7-azabicyclo[2.

2. l ]heptan - 7-yl )-1- ( 4-methylthiazol-5-yl ) pyrido[2,3-d]pyrimidin-2- one; formic acid 4-amino-7-cyclopropyl-1-(3-hydroxycyclopentyl )pyrido[2,3-d]pyrimidin-2( IH)-one 4-amino-7-(difluoromethoxy)-l -(2-methylpyridin-3-yl)quinazolin-2(1H)-one 4-amino-7-(difluoromethyl)-l -(2-methylpyridin-3-yl)quinazolin-2(1H)-one 4-amino-7-[(1R,2S)-2-fl uorocyclopropyl ]-1-(2-methyl-3-pyridyl )pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -(2-methylpyridin-3-yl)-2-oxo-l,2-dihydropyrido[2,3-d]pyrimidine-6- carbonitrile 3- ( 4-amino - 7-isopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H) -yl ) -2-methoxybenzonitrile 4-amino-7-cyclopropyl-2-oxo-l -(o-tolyl)-l ,2-dihydropyrido[2,3-d]pyrimidine-5-carbonitrile 4-amino-7-methoxy-l -(2-methylpyridin-3-yl)quinazolin-2(1H)-one 4-amino-1-(2-methyl pyridin-3-yl )-7-(trifluoromethoxy )quinazolin-2( IH)-one 4-amino-7-(4,5-dihydrofuran-3-yl)-l -(2-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-1-(2-methyl pyridin-3-yl )-7-(tetrahydrofuran-3-yl )pyrido[2,3-d]pyrimidin-2( IH)-one 4-amino-7-cyclopropyl-l -(2-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -(2-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-( 4-methylthiazol-5-yl )pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-( 4-methylpyrimidin-5-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-1-(2-( trifluoromethyl )pyridin-3-yl )pyrido[2,3-d]pyrimidin-2( IH)-one 4-amino-7-cyclopropyl-l -(2-methylpyrazol-3-yl)pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -(2,3-dihydrobenzofuran-4-yl)quinazolin-2(1H)-one (R)-4-amino-l -(tetrahydro-2H-pyran-3-yl)-7-(trifluoromethyl)quinazolin-2(1H)-one 4-amino-7-cyclopropyl-1-( 4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-ethyl-l -(2-methylpyridin-3-yl)quinazolin-2(1H)-one 4-amino-7-[(1S,2R)-2-fluorocyclopropyl]-l -[(3R)-tetrahydropyran-3-yl ]pyrido[2,3- d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-( 4-methyloxazol-5-yl)pyrido[2,3-d]pyrimidin-2-one 3-(4-amino-6-chloro- 7-isopropyl-2-oxopyrido[2,3-d]pyrimidin-l (2H)-yl)-2- methoxybenzonitrile 4-amino-7-cyclopropyl-1-((R)-l -((S)-tetrahydrofuran-3-yl)ethyl)pyrido[2,3-d]pyrimidin-2(1H)- one 4-amino-7-cyclopropyl-1-((R)-1-((R)-tetrahydrofuran-3-yl)ethyl )pyrido[2,3-d]pyrimidin-2(1H)- one 4-amino-7-(2-fluoropropan-2-yl)-l -(2-methylpyridin-3-yl)quinazolin-2-one 4-amino-5-methoxy-1-(2-methyl pyridin-3-yl )-7-(trifluoromethyl )quinazolin-2(IH)-one 4-amino-7-cyclopropyl-1-( 4-fluoro-2-methoxypyridin-3-yl )pyrido[2,3-d]pyrimidin-2( IH)-one 4-amino-5-fluoro-1-(2-methyl pyridin-3-yl )-7-(trifluoromethyl )quinazolin-2(IH)-one 4-amino-7-cyclopropyl-l -(l-ethyl-1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-chloro-1-(o-tolyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(2,3-dihydrobenzofuran-7-yl)pyrido[2,3-d]pyrimidin-2(1H)-one l-amino-4-(2-methoxyphenyl)-6-(trifluoromethyl)-3H-pyrido[l,2-c]pyrimidin-3-one 4-amino-1-(2-chlorophenyl)- 7-cyclopropylpyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-[ (IR)-1-[(3S)-oxolan-3-yl ]ethyl]pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-[ (IR)-1-[(3R)-oxolan-3-yl ]ethyl]pyrido[2,3-d]pyrimidin-2-one 3-(4-amino-6-chloro- 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin-l (2H)-yl)-2- methoxybenzonitrile 4-amino-7-cyclopropyl-l -(4-oxaspiro[2.5]octan-8-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-6-chloro- 7-cyclopropyl-1-(2-methoxypyridin-3-yl )pyrido[2,3-d]pyrimidin-2( IH)-one 4-amino-7-cyclopropyl-1-( 4-fluoro-2-methylphenyl )pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -(3-ethylphenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(m-tolyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-1-(3 ,5-difluorophenyl )pyrido[2,3-d]pyrimidin-2( IH)-one 4-amino-7-cyclopropyl-1-( 6-methoxypyridin-2-yl )pyrido[2,3-d]pyrimidin-2( IH)-one 4-amino-7-cyclopropyl-l -(3-methoxyphenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(2,3-difluorophenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -phenylpyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-1-(1-( oxazol-5-yl)ethyl)pyrido[2,3-d]pyrimidin-2(1H)-one 3-(4-amino-2-oxo-7-(trifluoromethyl)quinazolin-1(2H)-yl)-2-methylbenzonitrile 3-(4-amino-2-oxo-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-1(2H)-yl)-2-methylbenzonitrile 4-amino-7-cyclopropyl-l -(2,6-difluorophenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(2-fluorophenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(3-fluorophenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-1-[ 1-( oxetan-3-yl)ethyl ]pyrido[2,3-d]pyrimidin-2-one 4-amino-7-(difluoromethoxy)-1-(2-methylphenyl )pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -(l-pyridin-2-ylethyl)pyrido[2,3-d]pyrimidin-2-one 4-amino-1-(2-methyl-3-pyridyl)- 7-(2,2,2-trifluoroethyl)quinazolin-2-one hydrochloride 4-amino-7-cyclopropyl-l -(tetrahydro-2H-pyran-4-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-1-(2-chloropyridin-3-yl )-7-cyclopropyl pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-2-cyclopentyl-7-(2-methyl-3-pyridyl)pyrazolo[3,4-d]pyrimidin-6-one 4-amino-5-chloro-1-(2-methyl pyridin-3-yl )-7-(trifluoromethyl )quinazolin-2(lH)-one 4-amino-1-(3-fluoro-2-methyl phenyl)- 7-(trifluoromethyl )pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-7-cyclopropyl-l -(1H-indol-4-yl)pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -[6-(trifluoromethoxy)pyridin-2-yl]pyrido[2,3-d]pyrimidin-2-one 4-amino-1-(2,3-dihydrobenzofuran-4-yl )-7-(trifluoromethyl )pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-1-(3-chloro-2-fluorophenyl )-7-cyclopropyl pyrido[2,3-d]pyrimidin-2-one 4-amino-1-(2,3-dihydro-l -benzofuran-4-yl )-7-(trifluoromethoxy)quinazolin-2-one 4-amino-1-(3-fluoro-2-methyl phenyl)- 7-(trifluoromethoxy )quinazolin-2-one 3-[4-amino-2-oxo- 7-(trifluoromethoxy)quinazolin-l -yl]-2-methylbenzonitrile 4-amino-7-cyclopropyl-l -(2,3-dihydro-1H-indol-4-yl)pyrido[2,3-d]pyrimidin-2-one 4-amino-1-(2-chloro-5-fluorophenyl )-7-cyclopropyl pyrido[2,3-d]pyrimidin-2-one 4-amino-1-(2-chloro-4-fluorophenyl )-7-cyclopropyl pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-7-cyclopropyl-1-(2,5-difluorophenyl )pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-7-(ethylamino )-1-( o-tolyl)quinazolin-2-one 4-amino-1-(3-chlorophenyl)- 7-cyclopropylpyrido[2,3-d]pyrimidin-2(1H)-one 3-(4-amino-7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin-1(2H)-yl)benzonitrile 4-amino-7-(difluoromethoxy)-1-( 4-oxaspiro[2. 5]octan-8-yl)quinazolin-2(1H)-one l-amino-4-(2-chlorophenyl)-6-(trifluoromethyl)pyrido[l,2-c]pyrimidin-3-one 4-amino-1-(benzo[ d]oxazol-4-yl)- 7-cyclopropylpyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(3,4-difluorophenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 3- ( 4-amino - 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H) -yl ) -2-methylbenzonitrile 3- ( 4-amino - 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H) -yl ) -2-methylbenzonitrile 4-amino - 7- ( difluoromethoxy )-1-( o-tolyl ) quinazolin-2 (1H) -one 3- ( 4-amino - 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H) -yl ) -2-chlorobenzonitrile 4-amino - 7-cyclopropyl-1-[ ( 8 S) -4-oxaspiro[2. S]octan-8-yl ]pyrido[2,3-d]pyrimidin-2-one 4-amino - 7-cyclopropyl-1-[ ( 8R ) -4-oxaspiro[2. S]octan-8-y l ]pyrido[2,3-d]pyrimidin-2-one 4-amino-1- ( lH-benzo[ d]imidazol-4-yl )- 7-cyclopropylpyrido[2,3-d]pyrimidin-2 (1H) -one 4-amino-7-cyclopropyl-l -( 1H-indazol-4-yl ) pyrido[2,3-d]pyrimidin-2 (1H) -one 14. ترکیب طبق هر یک از ادعاهای 1 تا 12، انتخاب شده از گروه زیر تشکیل شده است : 4-amino- 7-cyclopropyl-1-( o-tolyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(2-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 3-(4-amino-7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H)-yl)-2-methylbenzonitrile 4-amino-7-cyclopropyl-1-(2,3-dihydrobenzofuran-4-yl )pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-7-cyclopropyl-1-(3-fluoro-2-methyl phenyl )pyrido[2,3-d]pyrimidin-2(lH)-one 4-amino-7-cyclopropyl-1-( oxan-3-yl)pyrido[2,3-d]pyrimidin-2-one 4-amino-7-(difluoromethoxy)-l -(2-methylpyridin-3-yl)quinazolin-2(1H)-one 4-amino-1-(2-methyl pyridin-3-yl )-7-(trifluoromethoxy )quinazolin-2( lH)-one 4-amino-7-cyclopropyl-l -(2,3-dihydrobenzofuran-4-yl)quinazolin-2(1H)-one 4-amino-7-cyclopropyl-l -(2,3-dihydrobenzofuran-7-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-1-(2-chlorophenyl)- 7-cyclopropylpyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -(4-oxaspiro[2.5]octan-8-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-1-(2-chloropyridin-3-yl )-7-cyclopropyl pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-7-(difluoromethoxy)-1-(2-methylphenyl )pyrido[2,3-d]pyrimidin-2-one 3-(4-amino-2-oxo-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-1(2H)-yl)-2-methylbenzonitrile 4-amino-7-cyclopropyl-l -(m-tolyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-1-[ (8S)-4-oxaspiro[2. S]octan-8-yl ]pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-[ (8R)-4-oxaspiro[2. S]octan-8-yl]pyrido[2,3-d]pyrimidin-2-one (R)-4-amino-7-cyclopropyl-1-( oxepan-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-1-((2S,3R)-2-methyltetrahydro-2H-pyran-3-yl )pyrido[2,3-d]pyrimidin-2( lH)- one 4-amino- 7-cyclopropyl-l -(2,3-dimethylphenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-1-(2-chloropyridin-3-yl )-7-(difluoromethoxy)quinazolin-2(lH)-one 4-amino-1-(2-chloropyridin-3-yl )-7-cyclopropyl pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino-1-(2-chloropyridin-3-yl )-7-cyclopropyl pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino- 7-(difluoromethoxy)-l-(m-tolyl)quinazolin-2(1H)-one 4-amino- 7-(difluoromethoxy)-l -(2-fluoro-3-methylphenyl)quinazolin-2(1H)-one 4-amino-7-cyclopropyl-l -(2-(trifluoromethyl)phenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(3-(fluoromethyl)-2-methylphenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-l -(2-chloro-3-methylphenyl)-7-cyclopropylpyrido[2,3-d]pyrimidin-2-one 4-amino-1-(3-chloro-2-methyl phenyl)-7-cyclopropyl pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-l -(2,3-dichlorophenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l -(2-fluoro-3-methylphenyl)pyrido[2,3-d]pyrimidin-2(1H)-one 3-(4-amino- 7-cyclopropyl-2-oxopyrido[2,3-d]pyrimidin- l (2H)-yl)-2-fluorobenzonitrile (S)-4-amino- 7-cyclopropyl-1-(oxepan-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one (R)-4-amino- 7-cyclopropyl-1-(oxepan-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino- 7-cyclopropyl-1-(3-hydroxy-2-methyl phenyl )pyrido[2,3-d]pyrimidin-2( lH)-one 4-amino- 7-(difluoromethoxy)-l -(3-fluoro-2-methylphenyl)quinazolin-2(1H)-one 4-amino- 7-cyclopropyl-1-[ rac-(2S,3 S)-2-methyltetrahydropyran-3-yl ]pyrido[2,3-d]pyrimidin-2- one 4-amino-1-(benzo[ d]thiazol- 7-yl)-7-cyclopropylpyrido[2,3-d]pyrimidin-2(1H)-one 4-amino- 7-cyclopropyl-1-( (2S,3R)-2-methyltetrahydro-2H-pyran-3-yl )pyrido[2,3-d]pyrimidin- 2( 1H)-one 4-amino-7-cyclopropyl-l -((2R,3S)-2-methyltetrahydro-2H-pyran-3-yl)pyrido[2,3-d]pyrimidin- 2(1H)-one (-)-4-amino-l -(2-chloro-3-fluorophenyl)- 7-cyclopropylpyrido[2,3-d]pyrimidin-2(1H)-one (+ )-4-amino-1-(2-chloro-3-fluorophenyl)- 7-cyclopropylpyrido[2,3-d]pyrimidin-2(1H)-one (-)-4-amino-l -(2-chlorophenyl)-7-cyclopropylpyrido[2,3-d]pyrimidin-2(1H)-one (+ )-4-amino-1-(2-chlorophenyl)-7-cyclopropylpyrido[2,3-d]pyrimidin-2(1H)-one 4-amino- 7-cyclopropyl-6-( difluoromethoxy)-1-( o-tolyl)pyrido[2,3-d]pyrimidin-2-one 4-amino- 7-cyclopropyl-1-( 6,7-dihydro-SH-pyrrolo[ 1,2-c]imidazol- 7-yl)pyrido[2,3-d]pyrimidin- 2-one;formic acid 4-(2-chlorophenyl)-6-cyclopropyl-l -imino-pyrido[ 1,2-c]pyrimidin-3-one;formic acid 4-amino- 7-cyclopropyl-1-[2-( trifluoromethoxy )phenyl ]pyrido[2,3-d]pyrimidin-2-one 4-amino-1-(2-chloro-3-pyridyl)- 7-(trifluoromethoxy)quinazolin-2-one 4-amino-7-cyclopropyl-l-(6-(difluoromethoxy)pyridin-2-yl)pyrido[2,3-d]pyrimidin-2(1H)-one 4-amino-7-cyclopropyl-l-(l,4-dioxepan-6-yl)pyrido[2,3-d]pyrimidin-2-one 4-amino-7-cyclopropyl-1-(3-fluoro-2-methylphenyl)quinazolin-2-one 15. A compound according to any one of claims 1 to 14 for use as a therapeutic active ingredient.

16. Compounds of formula I or II according to any one of claims 1 to 14 or pharmaceutically acceptable salts thereof for use in the treatment, prevention and / or delaying the progression of lung oncocarcinoma, melanoma, pancreatic adenocarcinoma, head and neck squamous cell carcinoma, lung squamous cell carcinoma, esophageal carcinoma, glioblastoma multiforme and mesothelioma.