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Tittel PYRIMIDO- PYRIDAZINONE COMPOUNDS AND USE THEREOF
Status
Hovedstatus
Detaljstatus 		I kraft info EP patent gjort gjeldende i Norge EP patent besluttet gjeldende i Norge
Patentnummer NO/EP3392252
Europeisk (EP) publiserings nummer EP3392252
EP levert
EP søknadsnummer 18175788.1
EP meddelt
Avdelt fra EP2748166
Prioritet 2011.08.23, US 201161526525 P
Sakstype Europeisk
Løpedag
Utløpsdato
Allment tilgjengelig
Validert i Norge
Innehaver Libertas Bio, Inc. (US)
Oppfinner Venkatesan, Aranapakam (US) .... se mer/flere nedenfor
Fullmektig Budde Schou A/S (DK)
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Patentkrav1. Forbindelse med formel (I) for bruk i behandling av kreft, autoimmun sykdom, inflammatorisk sykdom, bensykdommer, metabolske sykdommer, nevrologiske og nevrodegenerative sykdommer, kardiovaskulære sykdommer, allergier, astma, Alzheimers sykdom, hormonrelaterte sykdommer, revmatoid artritt og faste og hematologiske maligniteter, hvorved forbindelsen med formel (I) administreres til en pasient i en terapeutisk effektiv mengde:hvor:R1 er NR4R5, eventuelt substituert C1 til C6 alkoksy, eventuelt substituert C6 til C14 aryl, eventuelt substituert heteroaryl, eventuelt substituert 3-10-leddet monocyklisk eller bicyklisk cykloalkyl, eller eventuelt substituert 3-10-leddet monocyklisk eller bicyklisk heterocyklisk, hvor:(i) 3-4-leddet cykloalkyl og heterosyklyl er mettet;(ii) hydrogenatomer på samme karbonatom i nevnte cykloalkyl eller heterocyklyl er eventuelt erstattet med en eventuelt substituert 3-6-leddet cykloalkyl eller heterocyklyl for å danne en spirocykloalkyl eller spiroheterocyklyl; og(iii) hydrogenatomer på det samme atom i nevnte cykloalkyl eller heterocyklyl er eventuelt erstattet med O for å danne en oksosubstituent;R2 er eventuelt substituert fenyl, -O- (C1 til C6 alkyl) eventuelt substituert fenyl, eller eventuelt substituert 5-6-leddet heteroaryl, med det forbehold at når R2 er 4-pyridyl, mangler 4-pyridyl en karbonylsubstituent i 2. posisjon;R4 og R5 er: (a) uavhengig valgt fra gruppen bestående av H, C1 til C6 alkyl, C1 til C6 hydroksyalkyl, C3 til C8 cykloalkyl og -(C1 til C6 alkyl)N(C1 til C6 alkyl)(C1 til C6 alkyl); eller(b) sammenføyde for å danne en eventuelt substituert 3-8-leddet heterocyklyl, hvor;(bi) hydrogenatomer på samme karbonatom i nevnte heterocyklyl er eventuelt erstattet med en eventuelt substituert 3-6-leddet cykloalkyl eller heterocyklyl for å danne en spirocykloalkyl eller spiroheterocyklyl; og (bii) hydrogenatomer på det samme atom av nevnte heterocyklyl (b), cykloalkyl (bi) eller heterocyklyl (bi), er eventuelt erstattet med O for å danne en oksosubstituent; eller et farmasøytisk akseptabelt salt eller ester derav. 2. Forbindelse for bruk i henhold til krav 1, hvor den autoimmune sykdommen er en eller flere av transplantasjonsavvisning, revmatoid artritt, amyotrofisk lateralsklerose, multippel sklerose og vaskulitt.3. Forbindelse for bruk i henhold til krav 1, hvor R2 er fenyl substituert med C(O)NR4R5.4. Forbindelse for bruk i henhold til krav 1, hvor R2 er fenyl substituert med NR4R5.5. Forbindelse for bruk ifølge krav 1, hvor R2 er fenyl substituert med (C1 til C6 alkyl)NR4R5.6. Forbindelse for bruk i henhold til krav 1, hvor R4 og R5 er sammenføyet for å danne et eventuelt substituert piperidin eller diazepan.7. Forbindelse for bruk ifølge krav 1, hvor R2 er fenyl substituert med (C1 til C6 alkyl)NR4R5.8. Forbindelse for bruk ifølge krav 7, hvor R4 og R5 er (C1 til C6 hydroksyalkyl). 9. Forbindelse for bruk i henhold til krav 4, hvor R4 og R5 er sammenføyet for å danne en eventuelt substituert 6-leddet ring.10.Forbindelse for bruk ifølge krav 1, hvor R2 er et heteroaryl substituert med (C1 til C6 alkyl)NR4R5.11.Forbindelse for bruk ifølge krav 1, hvor R2 er et heteroaryl substituert med NR4R5.12.Forbindelse for anvendelse ifølge krav 1, hvor R2 er fenyl substituert med én eller flere C1 til C6 alkoksy, (C1 til C6 alkyl)halogen, C1 til C6 trifluoralkoksy, (C1 til C6 alkyl)C(O)OH, halogen, eventuelt substituert C3 til C8 cykloalkyl, eventuelt substituert heterosyklyl, eventuelt substituert heteroaryl, -O- (C1 til C6 alkyl)C(O)OH, -O- (C1 til C6 alkyl) -NR 4R5, -O- (eventuelt substituert heterosyklus), -O (C1 til C6 alkyl) -N (C1 til C6 alkyl)(C1 til C6 alkyl), -O- (C1 til C6 alkyl)NH2, C1 til C6 hydroksyalkyl, -O- (C1 til C6 hydroksyalkyl), O- (C1 til C6 alkyl) -C (O)OH, -C 1 til C6 alkoksy-C 1 til C6 alkoksy, O- (heterosyklus)-(C1 til C6 hydroksyalkyl), SO2-(C1 til C6 alkyl), eller -(C1 til C6 alkyl)-(C1 til C6 alkoksy)-halogen.13.Forbindelse for bruk ifølge krav 1, hvor R2 er fenyl substituert med -O-(C1 til C6 alkyl)-heterocyklus.14.Forbindelse for anvendelse ifølge krav 1, hvor R1 er N(C1 til C6 alkyl)(C1 til C6 alkyl) eller C1 til C6 alkoksy.15.Forbindelse for bruk ifølge krav 1, hvor R1 eventuelt er substituert fenyl.16.Forbindelse for bruk ifølge krav 1, hvor R1 eventuelt er substituert 5-9-leddet mettet heterocyklyl.17.Forbindelse for bruk i henhold til krav 1, hvor R1 er en heterocyklyl av strukturen:hvor:f, g, h, j og m er uavhengig fraværende, (CH2), CH(R3), Z eller C=O;R3 er H, C(O)OH eller C(O)O(C1 til C6 alkyl);R45, R46, R47 og R48 er, uavhengig av hverandre, H eller C1 til C6 alkyl; ogZ er O, S, SO, SO2 eller NH.Forbindelse for bruk ifølge krav 1, hvor R1 er en heteroaryl. Forbindelse for bruk ifølge krav 1, hvor R1 er en monocyklisk C3 til C8 sykloalkyl.Forbindelse for bruk ifølge krav 1, hvor R1 er piperidin substituert med C(O)(C1 til C6 alkyl)CN.Forbindelse for bruk i henhold til krav 1, hvor forbindelsen er et salt av en syre.Forbindelse for bruk ifølge krav 21, hvor nevnte syre er valgt fra gruppen bestående av eddiksyre, propionsyre, melkesyre, sitronsyre, vinsyre, ravsyre, fumarsyre, maleinsyre, malonsyre, mandelsyre, eplesyre, ftalsyre, saltsyre, hydrobromsyre, fosforsyre, salpetersyre, svovelsyre, metansulfonsyre, naftalensulfonsyre, benzensulfonsyre, toluensulfonsyre, trifluoreddiksyre og kamfersulfonsyre.Forbindelse for bruk i henhold til krav 1, hvor forbindelsen er:4-(4-morfolinofenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;metyl-4- (5-okso-4- (4-(piperazin-1-ylmetyl)fenylamino)-5,6-dihydropyrimido[4,5-d] pyridazin-2-yl) benzoathydroklorid; 2-morfolino-4-(4-(piperazin-1-ylmetyl)fenylamino)pyrimido[4,5-d]pyridazin-5 (6H) -onhydroklorid;4-(4-(morfolinometyl)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;4-(4-(4-etylpiperazin-1-yl)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on; 4-(4-((4-etylpiperazin-1-yl)metyl)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;2-fenyl-4-(4-(piperazin-1-ylmetyl)fenylamino)pyrimido[4,5-d]pyridazin-5 (6H) -on-hydroklorid;2-fenyl-4-(4-(piperazin-1-yl)fenylamino)pyrimido[4,5-d]pyridazin-5(6H)-on;4-(4-(morfolin-4-karbonyl)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;4-(4-(bis(2-hydroksyetyl)amino)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;4-(4-(4-(2-aminoacetyl)piperazin-1-yl)fenylamino)-2-fenylpyrimido [4,5-d]pyridazin-5 (6H) -on-hydroklorid;2-(4-(4-(5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d] pyridazin-4-ylamino)fenyl) piperazin-1-yl)eddiksyre;1-(4-(5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d] pyridazin-4-ylamino)fenyl) piperidin-4-karboksylsyre;4-(4-(4-(2-aminoacetyl)piperazin-1-yl)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;N-(2-(dimetylamino)etyl)-N-metyl-4-(5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d]pyridazin-4-ylamino)benzamid;4-(4-(2-okso-1,7-diazaspiro[3.5]nonan-7-yl)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;4-(4-(2-oksa-7-azaspiro[3.5]nonan-7-yl)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;4-(4-morfolinofenylamino)-2-(6-azaspiro[2,5]oktan-6-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;6-(4-(5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d]pyridazin-4-ylamino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre; etyl-6- (4- (5-okso-2-fenyl-5,6-dihydropyrimido [4,5-d]pyridazin-4-ylamino)fenyl)-6-azaspiro[2,5]oktan-1-karboksylat;6-(4-(5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d]pyridazin-4-ylamino)benzyl)-6-azaspiro [2,5] oktan-1-karboksylsyre; natrium-6- (4- (5-okso-2-fenyl-5,6-dihydropyrimido [4,5-d]pyridazin-4-ylamino)fenyl)-6-azaspiro[2,5]oktan-1-karboksylat;4-(4-(2-oksa-7-azaspiro[3.5]nonan-7-ylmetyl)fenylamino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;4-(4-(piperazin-1-ylmetyl)fenylamino)-2-(tiofen-3-yl)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;6-(5-okso-4-(4-(piperazin-1-ylmetyl)fenylamino)-5,6-dihydropyrimido [4,5-d] pyridazin-2-yl) -6-azaspiro [2,5] oktan-1-karboksylsyre-hydroklorid;4-(4-(4-etylpiperazin-1-yl)fenylamino)-2-morfolinopyrimido[4,5-d]pyridazin-5(6H)-on;4-(5-okso-4-(4- (piperazin-1-ylmetyl)fenylamino)-5,6-dihydropyrimido [4,5-d] pyridazin-2-yl)benzosyrehydroklorid; 4-(4-(4-etylpiperazin-1-yl)fenylamino)-2-(4-(trifluormetoksy)fenyl)pyrimido[4,5-d]pyridazin-5(6H)-on; metyl-4- (4- (4-morfolinofenylamino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)benzoat;4-(4-(piperazin-1-ylmetyl)fenylamino)-2-(piperidin-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(3-metoksyfenyl)-4-(4-(piperazin-1-ylmetyl)fenylamino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(piperazin-1-yl)-4-(4-(piperazin-1-ylmetyl)fenylamino)pyrimido[4,5-d]pyridazin-5(6H)-on dihydroklorid;2-(benzo[d][1,3]dioksol-5-yl)-4-(4-(piperazin-1-ylmetyl)fenylamino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(1-(4-(5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d] pyridazin-4-ylamino)fenyl) piperidin-4-yl)eddiksyre;1-(4-(5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d] pyridazin-4-ylamino)benzyl) piperidin-4-karboksylsyre; 2-(2-metoksyfenyl)-4-(4-(piperazin-1-ylmetyl)fenylamino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;4-(4-(4-etylpiperazin-1-yl)fenylamino)-2-(tiofen-3-yl)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;9-(5-okso-4-(4-(piperazin-1-ylmetyl)fenylamino)-5,6-dihydropyrimido[4,5-d] pyridazin-2-yl)-3,9-diazaspiro [5.5] undekan-2,4-dion-hydroklorid;6-(4-(5-okso-2-(tiofen-3-yl)-5,6-dihydropyrimido[4,5-d] pyridazin-4-ylamino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(4-klorfenyl)-4-(4-(piperazin-1-ylmetyl)fenylamino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(4-metoksyfenyl)-4-(4-(piperazin-1-ylmetyl)fenylamino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;6-(4-((2-morfolino-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(5-okso-4-((4- (piperazin-1-ylmetyl)fenyl)amino)-5,6-dihydropyrimido [4,5-d] pyridazin-2-yl)piperidin-4-yl) eddiksyrehydroklorid;2-(1-oksidotiomorfolino)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(4-metylpiperazin-1-yl)-4-(((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;6-(4-((2-(4-metoksyfenyl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre; 6-(4-((2-(3-metoksyfenyl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;4-((4-(piperazin-1-ylmetyl)fenyl)amino)-2-(pyrrolidin-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(dimetylamino)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-etoksy-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;1-(5-okso-4-((4- (piperazin-1-ylmetyl)fenyl)amino)-5,6-dihydropyrimido [4,5-d] pyridazin-2-yl) piperidin-4-karboksylsyre-hydroklorid;2-(azepan-1-yl)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;6-(4-((2-(2-metoksyfenyl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(diisopropylamino)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(4-(morfolinometyl)fenyl)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;1-(5-okso-4-((4-(piperazin-1-ylmetyl)fenyl)amino)-5,6-dihydropyrimido [4,5-d] pyridazin-2-yl) piperidin-4-karbonitrilhydroklorid;2-(4-etylpiperazin-1-yl)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;4-((1-(2-morfolinoetyl)-1H-pyrazol-4-yl)amino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1,4-diazepan-1-yl)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on dihydroklorid;2-(azepan-1-yl)-4-((4-morfolinofenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-metoksy-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5 (6H) -onhydroklorid;6-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-fenyl-4-((1-(2-(piperazin-1-yl)etyl)-1H-pyrazol-4-yl)amino)pyrimido[4,5-d]pyridazin-5 (6H) -on-hydroklorid; 4-((1-(2-(4-metylpiperazin-1-yl)etyl)-1H-pyrazol-4-yl)amino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;4-((1-(2-(4-etylpiperazin-1-yl)etyl)-1H-pyrazol-4-yl)amino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;6-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(azepan-1-yl)-4-((3,4,5-trimetoksyfenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(azepan-1-yl)-4-((4-(morfolin-4-karbonyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;2-(1-(4-((2-(4-(cyanometyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;2-(1-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre; 6-(4-((2-(1,4-diazepan-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl) amino) fenyl) -6-azaspiro [2,5] oktan-1-karboksylsyre-hydroklorid;6-(4-((2-(4-(cyanometyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;6-(4-((2-(4-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(4-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;1-(4-((2-(4-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-yl)eddiksyre;1-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;6-(4-((2-cykloheksyl-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril; 6-(4-((2-cykloheptyl-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril; 4-((4-((4-(2-hydroksy-2-metylpropanoyl)piperazin-1-yl)metyl)fenyl)amino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on; 2-(azepan-1-yl)-4-((4-((4-(2-hydroksy-2-metylpropanoyl)piperazin-1-yl)metyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-((4-metylpiperazin-1-yl)metyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(4-(4-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-1-yl)eddiksyre;2-(4-(4-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)cykloheksyl)eddiksyre;2-(1-(4-((2-(azocan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;2-(azepan-1-yl)-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(1-(4-((2-cykloheptyl-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;2-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)cykloheksyl)eddiksyre;4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenoksy)smørsyre;2-(azepan-1-yl)-4-((4-(2-morfolinoetoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;4-((4-(2-morfolinoetoksy)fenyl)amino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(4-metylpiperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(2-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenoksy)etyl) piperidin-4-yl)eddiksyre;2-(1-(5-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)pyridin-2-yl)piperidin-4-yl)acetonitril; 1-(2-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenoksy)etyl) piperidin-4-karboksylsyre;2-(1-(5-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)pyridin-2-yl)piperidin-4-yl)acetamid;2-(1-(4-((2-(4-(2-cyanopropan-2-yl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;2-(1-(5-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)pyridin-2-yl)piperidin-4-yl)acetonitril;2-(1-(5-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)pyridin-2-yl)piperidin-4-yl)acetamid;2-(1-(5-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)pyridin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(piperazin-1-karbonyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetamid;2-(4-(2-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenoksy)etyl) piperazin-1-yl)eddiksyre;2-(azepan-1-yl)-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(5-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperidin-4-yl)eddiksyre;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)-N-(2-hydroksyetyl)acetamid; 2-(azepan-1-yl)-4-((4-(((2S,5S)-5-(hydroksymetyl)-1,4-dioksan-2-yl)metoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5 (6H)-on;2-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperazin-1-yl)-2-metylpropannitril;2-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperazin-1-yl)-2-metylpropanamid;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril; 2-(1-(5-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)pyridin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-(4-(2-hydroksy-2-metylpropanoyl)piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(5-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperidin-4-yl)eddiksyre;2-(1-(4-((2-(3,5-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)-N,N-bis(2-hydroksyetyl)acetamid;2-metyl-2-(1-(4-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)propannitril; 2-(4-(2-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenoksy)etyl)piperazin-1-yl)-2-metylpropannitril; 2-(1-(4-((2-(2,6-dimetylmorfolino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre; 4-((4-((2S,5S) -5- (hydroksymetyl) -1,4-dioksan-2-yl)metoksy)fenyl)amino)-2-fenylpyrimido[4,5-d]pyridazin-5(6H)-on;2-((1S,4S)-4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl)cykloheksyl)eddiksyre;(2R,5S)-5-((4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenoksy)metyl) -1,4-dioksan-2-karboksylsyre;2-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperazin-1-yl)eddiksyre;2-(1-(3-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenoksy)propyl) piperidin-4-yl)eddiksyre;6-(4-((2-(cykloheksylamino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)spiro[2,5] oktan-1-karboksylsyre;6-(4-((5-okso-2-(piperidin-1-yl)-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)spiro[2,5] oktan-1-karboksylsyre; 2-((1R,4R)-4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl)cykloheksyl)eddiksyre;3-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)propansyre;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)cyklopropankarboksylsyre;3-(1-(4-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)propansyre;6-(4-((2-(4-fluorfenyl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre; 6-(5-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl)-6-azaspiro [2,5] oktan-1-karboksylsyre;6-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) -2-fluorfenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(azepan-1-yl)-4-((4-(3-(piperazin-1-yl)propoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 6-(5-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino) pyridin-2-yl)-6-azaspiro [2,5] oktan-1-karboksylsyre;6-(4-((5-okso-2-(pyridin-4-yl)-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(azepan-1-yl)-4-((4-(4-(2-hydroksypropan-2-yl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperazin-1-yl) -2-metylpropansyre;6-(4-((2-(azokan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl) -2-metylpropansyre;2-metyl-2-(1-(4-((5-okso-2-fenyl-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)propansyre;2-(2,6-dimetylpiperidin-1-yl)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((2-(2,6-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre; 6-(4-((2-(2,6-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(2,6-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril;2-(2,6-dimetylpiperidin-1-yl)-4-((4-(4-(2-hydroksy-2-metylpropanoyl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(5-((2-(2,6-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperidin-4-yl)eddiksyre;2-(3,5-dimetylpiperidin-1-yl)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((2-(3,5-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;6-(4-((2-(3,5-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(3,5-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril;2-(3,5-dimetylpiperidin-1-yl)-4-((4-(4-(2-hydroksy-2-metylpropanoyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(5-((2-(3,5-dimetylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperidin-4-yl)eddiksyre;2-(2,6-dimetylmorfolino)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((2-(2,6-dimetylmorfolino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre; 6-(4-((2-(2,6-dimetylmorfolino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(2,6-dimetylmorfolino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril;2-(2,6-dimetylmorfolino)-4-((4-(4-(2-hydroksy-2-metylpropanoyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(5-((2-(2,6-dimetylmorfolino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperidin-4-yl)eddiksyre;2-(diisopropylamino)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((2-(diisopropylamino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;6-(4-((2-(diisopropylamino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(diisopropylamino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril;2-(diisopropylamino)-4-((4-(4-(2-hydroksy-2-metylpropanoyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(5-((2-(diisopropylamino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperidin-4-yl)eddiksyre;2-(2-metylpiperidin-1-yl)-4-((4-(piperazin-1-ylmetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((2-(2-metylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre; 6-(4-((2-(2-metylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(2-metylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril;4-((4-(4-(2-hydroksy-2-metylpropanoyl)piperidin-1-yl)fenyl)amino)-2-(2-metylpiperidin-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(5-((2-(2-metylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperidin-4-yl)eddiksyre;1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-karboksylsyre;1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;4-((4-((4-(2H-tetrazol-5-yl)piperidin-1-yl)metyl)fenyl)amino)-2-(azepan-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;4-((4-((4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)metyl)fenyl)amino)-2-(azepan-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((2-cykloheptyl-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;1-(4-((2-cykloheptyl-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-karboksylsyre;6-(4-((2-(3-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(3-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre; 1-(4-((2-(3-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-karboksylsyre;1-(4-((2-(3-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;1-(4-((4-((4-(2H-tetrazol-5-yl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-3-karbonitril;2-(1-(4-((2-(3-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-yl)eddiksyre;1-(4-((4-((4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-3-karbonitril;1-(4-((2-cykloheptyl-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;4-((4-((4-(2H-tetrazol-5-yl)piperidin-1-yl)metyl)fenyl)amino)-2-cykloheptylpyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((2-cykloheptyl-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-yl)eddiksyre;4-((4-((4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)metyl)fenyl)amino)-2-cykloheptylpyrimido[4,5-d]pyridazin-5(6H)-on;1-(4-((2-(4-cyanopiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-karboksylsyre;1-(4-((4-((4-(2H-tetrazol-5-yl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-karbonitril;1-(4-((4-((4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-karbonitril; 1-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;2-(1-(4-((4-((4-(2H-tetrazol-5-yl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-((4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;1-(4-((2-(4-(cyanometyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-karboksylsyre;1-(4-((2-(4-(cyanometyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;2-(4-(4-((4-((4-(2H-tetrazol-5-yl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperazin-1-yl)acetonitril;2-(1-(4-((2-(4-(cyanometyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-yl)eddiksyre;2-(4-(4-((4-((4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperazin-1-yl)acetonitril;6-(4-((2-(1,4-diazepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(1,4-diazepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;1-(4-((2-(1,4-diazepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-karboksylsyre; 1-(4-((2-(1,4-diazepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;6-(4-((2-(4-(2-cyanoacetyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(4-(2-cyanoacetyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;1-(4-((2-(4-(2-cyanoacetyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-karboksylsyre;1-(4-((2-(4-(2-cyanoacetyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;3-(4-(4-((4-((4-(2H-tetrazol-5-yl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperazin-1-yl)-3-oksopropannitril;2-(1-(4-((2-(4-(2-cyanoacetyl)piperazin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-yl)eddiksyre;4-((4-((4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)metyl)fenyl)amino)-2-(4-(2-isocyanoacetyl)piperazin-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;6-(4-((2-(1-(2-cyanoacetyl)piperidin-4-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(1-(4-((2-(1-(2-cyanoacetyl)piperidin-4-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;1-(4-((2-(1-(2-cyanoacetyl)piperidin-4-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-karboksylsyre; 1-(4-((2-(1-(2-cyanoacetyl)piperidin-4-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-karboksylsyre;3-(4-(4-((4-((4-(2H-tetrazol-5-yl)piperidin-1-yl)metyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-1-yl)-3-oksopropannitril;2-(1-(4-((2-(1-(2-cyanoacetyl)piperidin-4-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)benzyl) piperidin-4-yl)eddiksyre;4-((4-((4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)metyl)fenyl)amino)-2-(1-(2-isocyanoacetyl)piperidin-4-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(4-(5-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperazin-1-yl)eddiksyre;2-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) -1,4-diazepan-1-yl)eddiksyre; 2-(1-(4-((4-(4-(2-hydroksypropan-2-yl)piperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;3-(1-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)propansyre;6-(5-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino) pyridin-2-yl)-6-azaspiro [2,5] oktan-1-karboksylsyre;1-(5-okso-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-karbonitril;2-(1-(5-okso-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-(4-etylpiperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-fenyl-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)-2-(piperidin-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(4-(4-((5-okso-2-(piperidin-1-yl)-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) -1,4-diazepan-1-yl)eddiksyre;6-(4-((2-(4-metylpiperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(4-metylpiperidin-1-yl)-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(azepan-1-yl)-4-((4-(2-(3-oksopiperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 6-(2-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenoksy)etyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;2-(azepan-1-yl)-4-((4-(2-(dietylamino)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(cykloheksyl(metyl)amino)-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((2-(cykloheksyl(metyl)amino)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-4-yl)eddiksyre;2-(4-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperazin-1-yl)eddiksyre;2-(1-(4-((2-(3-metoksyfenyl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperidin-4-yl)acetonitril;4-((4-(2-(1,4-diazepan-1-yl)etoksy)fenyl)amino)-2-(azepan-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(azepan-1-yl)-4-((4-(3-oksopiperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(3-metoksyfenyl)-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(azepan-1-yl)-4-((4-(2-(dimetylamino)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(piperidin-4-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(5-okso-4-((4-(2-(piperidin-4-yl)etoksy)fenyl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;6-(4-((2-(cykloheksyl(metyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)-6-azaspiro [2,5] oktan-1-karboksylsyre;4-((4-(2-(1,4-diazepan-1-yl)etoksy)fenyl)amino)-2-(piperidin-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(4-hydroksypiperidin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(azepan-1-yl)-4-((4-(3-(piperazin-1-yl)propyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(5-okso-4-((4-(3-(piperazin-1-yl)propyl)fenyl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-etyl-3-oksopiperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-morfolino-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(2,6-dimetylmorfolino)-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((4-(4-etyl-3-oksopiperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril; 2-(azepan-1-yl)-4-((4-(3-(4-hydroksypiperidin-1-yl)propyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(azepan-1-yl)-4-((4-(4-etylpiperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;4-((6-(2-(piperazin-1-yl)etoksy)pyridin-3-yl)amino)-2-(piperidin-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((6-(2-(piperazin-1-yl)etoksy)pyridin-3-yl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;4-((4-(2-(4-hydroksypiperidin-1-yl)etoksy)fenyl)amino)-2-(piperidin-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(4-hydroksy-4-metylpiperidin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((4-(2-(4-hydroksy-4-metylpiperidin-1-yl)etoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-hydroksypiperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-etylpiperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-(diisopropylamino)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-hydroksypiperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-(2-hydroksyetyl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2-hydroksyetyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(5-okso-4-((4-(piperazin-1-yl)fenyl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-(3-hydroksypropyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(4-(2-hydroksyetyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2-hydroksyetyl)piperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-(2-(4-etylpiperazin-1-yl)etyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-(piperazin-1-yl)etyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;4-((4-(2-aminoetoksy)fenyl)amino)-2-(azepan-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(2-aminoetoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-(4-hydroksypiperidin-1-yl)etyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(4-(hydroksymetyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(4-(hydroksymetyl)piperidin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((4-(4-(3-hydroksypropyl)piperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperazin-1-yl)acetonitril; 2-(1-(4-((4-(4-(cyanometyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril; 3-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperazin-1-yl)propansyre;2-(azepan-1-yl)-4-((4-(2-(4-etylpiperazin-1-yl)etyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(4-hydroksy-4-metylpiperidin-1-yl)etyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(4-(2-hydroksyetyl)piperazin-1-yl)etyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(2-(4-(2-hydroksyetyl)piperazin-1-yl)etyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(4-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperazin-1-yl) -2-metylpropansyre;2-(azepan-1-yl)-4-((4-(4-(2-hydroksy-2-metylpropanoyl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;3-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperazin-1-yl)-3-oksopropannitril;2-(1-(4-((4-(4-(hydroksymetyl)piperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((6-(4-hydroksypiperidin-1-yl)pyridin-3-yl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(2-(4-(hydroksymetyl)piperidin-1-yl)etoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;(fosfonooksy)metyl-6- (4- ((2- (azepan-1-yl) -5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)-6-azaspiro[2,5]oktan-1-karboksylat;3-(4-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperazin-1-yl)propansyre; 2-(azepan-1-yl)-4-((6-(piperazin-1-yl)pyridin-3-yl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(2-hydroksyetyl)-2H-tetrazol-5-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2-hydroksy-2-metylpropanoyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-(2-(dietylamino)etoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-etyl-2H-tetrazol-5-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(2-etyl-2H-tetrazol-5-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;4-((4-(2H-tetrazol-5-yl)fenyl)amino)-2-(azepan-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((6-(4-etylpiperazin-1-yl)pyridin-3-yl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((6-(4-etylpiperazin-1-yl)pyridin-3-yl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(4-(5-okso-4-((4-(2-(piperazin-1-yl)etoksy)fenyl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperazin-1-yl)acetonitril;2-(1-(5-okso-4-((6-(piperazin-1-yl)pyridin-3-yl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-3-yl)eddiksyre;2-(1-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-3-yl)eddiksyre; 3-(4-(5-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)pyridin-2-yl)piperazin-1-yl)-3-oksopropannitril;2-(5-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl) -2H-tetrazol-2-yl)eddiksyre; 2-(azepan-1-yl)-4-((6-(4-(2-hydroksyetyl)piperidin-1-yl)pyridin-3-yl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 3-(4-(5-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)pyridin-2-yl)piperazin-1-yl)-3-oksopropannitril;2-(azepan-1-yl)-4-((6-(4-(2-hydroksy-2-metylpropanoyl)piperazin-1-yl)pyridin-3-yl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(2-(4-(2-hydroksyetyl)piperazin-1-yl)etoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 3-(4-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-4-yl)amino)fenyl)piperazin-1-yl)-3-oksopropannitril;2-(5-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) -2H-tetrazol-2-yl)eddiksyre;2-(azepan-1-yl)-4-((6-(4-metylpiperazin-1-yl)pyridin-3-yl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((6-(4-metylpiperazin-1-yl)pyridin-3-yl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;4-((4-(4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)fenyl)amino)-2-(azepan-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(2H-tetrazol-5-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril; 2-(1-(4-((4-(4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-metylpiperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-metylpiperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(5-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino) pyridin-2-yl) piperidin-3-yl)eddiksyre;2-(1-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl) piperidin-3-yl)eddiksyre;2-(1-(4-((6-(4-(2-hydroksy-2-metylpropanoyl)piperazin-1-yl)pyridin-3-yl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;4-((6-(4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)pyridin-3-yl)amino)-2-(azepan-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((6-(4-((2H-tetrazol-5-yl)metyl)piperidin-1-yl)pyridin-3-yl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(4-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenoksy) piperidin-1-yl)eddiksyre;2-(azepan-1-yl)-4-((4-(4-(2-metoksyetyl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2-metoksyetyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-(4-(2-aminoetyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril; 2-(azepan-1-yl)-4-((4-(1-(hydroksymetyl)-6-azaspiro[2,5]oktan-6-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(1-(hydroksymetyl)-6-azaspiro[2,5]oktan-6-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-(3-hydroksypropyl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(3-hydroksypropyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(4-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenoksy) piperidin-1-yl)eddiksyre;2-(azepan-1-yl)-4-((4-(4-(2-hydroksyetyl)-1,4-diazepan-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2-hydroksyetyl)-1,4-diazepan-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-(1-hydroksy-2-metylpropan-2-yl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(1-hydroksy-2-metylpropan-2-yl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-(2-(dimetylamino)etyl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2-(dimetylamino)etyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-(4-etylpiperazin-1-yl)-2-oksoetoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((4-(2-(4-etylpiperazin-1-yl)-2-oksoetoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-(2-(4-metylpiperazin-1-yl)-2-oksoetoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(3-(2-hydroksyetyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(4-(2,3-dihydroksypropyl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2,3-dihydroksypropyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-(2-fluoretyl)piperazin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2-fluoretyl)piperazin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((6-(3-hydroksypiperidin-1-yl)pyridin-3-yl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((6-(3-hydroksypiperidin-1-yl)pyridin-3-yl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4,4-difluorpiperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4,4-difluorpiperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(3-hydroksypiperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(3-hydroksypiperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril; 2-(azepan-1-yl)-4-((4-(2-(4-metylpiperazin-1-yl)-2-oksoetoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((4-(3-(hydroksymetyl)piperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(3-(hydroksymetyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(3-(2-hydroksyetyl)piperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-(4-metoksypiperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-metoksypiperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(4-fluorpiperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-fluorpiperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-((1-(2-hydroksyetyl)piperidin-4-yl)oksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(piperidin-4-yloksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on hydroklorid;2-(1-(4-((4-(2-hydroksyetoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-hydroksyetoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((4-(3-hydroksypropoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(3-hydroksypropoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(1-hydroksy-2-metylpropan-2-yl)-1,4-diazepan-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(4-(2-fluoretyl)piperidin-1-yl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(4-(2-fluoretyl)piperidin-1-yl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((3,5-dimetoksyfenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(5-okso-4-((4-(trifluormetoksy)fenyl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((3,5-dimetoksyfenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-(trifluormetoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;3-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenyl)propansyre;3-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenyl)propansyre;2-(azepan-1-yl)-4-((4-(bis(2-hydroksyetyl)amino)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((4-(bis(2-hydroksyetyl)amino)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(3-hydroksypropyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(3-hydroksypropyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((3-(hydroksymetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((3-(hydroksymetyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-fluorfenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-fluorfenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(azepan-1-yl)-4-((4-((1-hydroksy-2-metylpropan-2-yl)oksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-((1-hydroksy-2-metylpropan-2-yl)oksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(4-((2-(azepan-1-yl)-5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-4-yl)amino)fenoksy) -2-metylpropansyre;2-(4-((2-(4-(cyanometyl)piperidin-1-yl)-5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-4-yl)amino)fenoksy) -2-metylpropansyre;2-(azepan-1-yl)-4-((3,4-dimetoksyfenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((3,4-dimetoksyfenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((3-metoksyfenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((3-metoksyfenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-hydroksyetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; 2-(1-(4-((4-(2-hydroksyetyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(2-metoksyetoksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(2-metoksyetoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(5-okso-4-((3,4,5-trimetoksyfenyl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-(benzo[d][1,3]dioksol-5-ylamino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-(benzo[d][1,3]dioksol-5-ylamino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-((1-(2-hydroksyetyl)piperidin-4-yl)oksy)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on; natrium (2-(4-(cyanometyl)piperidin-1-yl)-4-((4-(4-hydroksypiperidin-1-yl)fenyl)amino)-5-oksopyrimido [4,5-d]pyridazin-6 (5H) -yl) metylfosfat; 2-(azepan-1-yl)-4-((4-(hydroksymetyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((4-(hydroksymetyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-(metylsulfonyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(azepan-1-yl)-4-((4-(metylsulfonyl)fenyl)amino)pyrimido[4,5-d]pyridazin-5(6H)-on;2-(1-(4-((1H-benzo[d][1,2,3]triazol-5-yl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(5-okso-4-((2-okso-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-(3-fluorpropyl)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril;2-(1-(4-((4-(difluormetoksy)fenyl)amino)-5-okso-5,6-dihydropyrimido[4,5-d]pyridazin-2-yl)piperidin-4-yl)acetonitril; eller4-((1H-benzo[d][1,2,3]triazol-5-yl)amino)-2-(azepan-1-yl)pyrimido[4,5-d]pyridazin-5(6H)-on.Forbindelse for anvendelse ifølge krav 1, hvor forbindelsen er 2- (1- (4- ((4- (4-hydroksypiperidin-1-yl)fenyl)amino) -5-okso-5,6-dihydropyrimido[4,5-d] pyridazin-2-yl)piperidin-4-yl)acetonitril, eller et farmasøytisk akseptabelt salt derav.Forbindelse for bruk ifølge krav 1, hvor forbindelsen er 2-(1- (4- ((4- (4- (2-hydroksyetyl) piperazin-1-yl)fenyl)amino) -5-okso-5,6-dihydropyrimido [4,5-d] pyridazin-2yl)piperidin-4-yl)acetonitril, eller et farmasøytisk akseptabelt salt derav.Forbindelse for bruk ifølge krav 1, hvor behandlingen omfatter administrering av en farmasøytisk sammensetning som omfatter forbindelsen og en farmasøytisk akseptabel bærer. Forbindelse for bruk i henhold til krav 1, hvor nevnte behandling er ved inhibering av JAK-2- og SYK-banene.Sammensetning for bruk i behandling av kreft, autoimmun sykdom, inflammatorisk sykdom, bensykdommer, metabolske sykdommer, nevrologiske og nevrodegenerative sykdommer, kardiovaskulære sykdommer, allergier, astma, Alzheimers sykdom, hormonrelaterte sykdommer, revmatoid artritt og faste og hematologiske maligniteter, hvor nevnte behandling omfatter administrering til en pasient av en terapeutisk effektiv mengde av en forbindelse med formel (I) for bruk i henhold til noen av kravene 1 til 27, eller et farmasøytisk akseptabelt salt eller ester derav.Sammensetningen i krav 28, hvor den autoimmune sykdommen er en eller flere av transplantasjonsavvisning, revmatoid artritt, amyotrofisk lateralsklerose, multippel sklerose og vaskulitt.Et sett som omfatter en eller flere doseringsformer for bruk i behandling av kreft, autoimmun sykdom, inflammatorisk sykdom, bensykdommer, metabolske sykdommer, nevrologiske og nevrodegenerative sykdommer, kardiovaskulære sykdommer, allergier, astma, Alzheimers sykdom, hormonrelaterte sykdommer, revmatoid artritt og faste og hematologiske maligniteter, og instruksjoner for administrering av doseringsformene til et individ, hvor doseringsformene omfatter en forbindelse med formel (I) for bruk i henhold til noen av kravene 1 til 27,eller et farmasøytisk akseptabelt salt eller ester derav. Settet i krav 30, hvor den autoimmune sykdommen er en eller flere av transplantasjonsavvisning, revmatoid artritt, amyotrofisk lateralsklerose, multippel sklerose og vaskulitt. En doseringsform for bruk i behandling av kreft, autoimmun sykdom, inflammatorisk sykdom, bensykdommer, metabolske sykdommer, nevrologiske og nevrodegenerative sykdommer, kardiovaskulære sykdommer, allergier, astma, Alzheimers sykdom, hormonrelaterte sykdommer, revmatoid artritt og faste og hematologiske maligniteter, omfattende en forbindelse med formel (I) for bruk i henhold til noen av kravene 1 til 27, eller et farmasøytisk akseptabelt salt eller ester derav. Doseringsformen i krav 32, hvor den autoimmune sykdommen er en eller flere av transplantasjonsavvisning, revmatoid artritt, amyotrofisk lateralsklerose, multippel sklerose og vaskulitt.
Hva betyr A1, B, B1, C osv? info

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Innehaver i EP:
Libertas Bio, Inc.
997 Lenox Drive, Suite 220 Princeton Pike Corporate Center Lawrenceville, NJ 08648 US

Oppfinner(e) info chevron_right

Venkatesan, Aranapakam
97-07 63rd Road, Apt. 9K Rego Park, NY 11374 US
Smith, Roger Astbury
206 Bayberry Drive Chester Springs, PA 19425 US
Hosahalli, Subramanya
A-103 Temple Meadows No. 3 27th Cross Banashankari II Stage 560070 Bangalore IN
Potluri, Vijay
F 202 MIG-II 686 Srinivasa Plaza KPHB Colony 500072 Hyderabad Andhra Pradesh IN
Panigrahi, Sunil Kumar
Kantamal AT/PO Boudh District 762017 Orissa IN
Basetti, Vishnu
F 213 Block II RBR Complex Miyapur 500049 Hyderabad Andhra Pradesh IN
Kuntu, Karunasree
H.No: 8-3-231/422B Sri Krishna Nagar Yousufguda 500045 Hyderabad Andhra Pradesh IN

Fullmektig info chevron_right

Fullmektig i Norge:
Budde Schou A/S
Dronningens Tværgade 30 1302 KØBENHAVN K DK
Din referanse: 169302/BT/SD
Fullmektig i EP:
Stolmár & Partner Patentanwälte PartG mbB
Blumenstraße 17 80331 München DE

Prioritet info chevron_right

2011.08.23, US 201161526525 P

Anførte dokumenter info chevron_right

DE-A1- 2 046 577 (B1)

EP-A1- 1 970 373 (B1)

WO-A1-2011/053861 (B1)

WO-A1-2010/038060 (B1)

JP-A- 50 101 387 (B1)

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Statushistorie

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EP patent gjort gjeldende i Norge EP patent besluttet gjeldende i Norge
EP under behandling Forespørsel om å gjøre EP patent gyldig er mottatt

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Utgående EP Registreringsbrev (3210) (PTEP3392252)
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Innkommende, AR591032002 Søknadsskjema Patent
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01-02 EP Krav NOEP3392252_Norwegian claims
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Årsavgift 14. avg. år (EP) 5850,0 Totalbeløp 5850,0   Gå til betaling

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Årsavgift 13. avg. år (EP) 2024.08.28 5460 COMPUTER PACKAGES INC. Betalt og godkjent
32400410 expand_more 2024.01.05 5580 Budde Schou A/S Betalt
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Kapitler uten data er fjernet. Melding opprettet: 26.04.2025 17:46:39