RS68232B1 - Inhibitori tirozin kinaze - Google Patents

Inhibitori tirozin kinaze

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Publication number
RS68232B1
RS68232B1 RS20260742A RSP20260742A RS68232B1 RS 68232 B1 RS68232 B1 RS 68232B1 RS 20260742 A RS20260742 A RS 20260742A RS P20260742 A RSP20260742 A RS P20260742A RS 68232 B1 RS68232 B1 RS 68232B1
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Serbia
Prior art keywords
amino
pyridin
imidazo
oxo
dihydro
Prior art date
Application number
RS20260742A
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English (en)
Inventor
David Goldstein
Timothy D Owens
Original Assignee
Principia Biopharma Inc
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Publication date
Application filed by Principia Biopharma Inc filed Critical Principia Biopharma Inc
Publication of RS68232B1 publication Critical patent/RS68232B1/sr

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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Claims (7)

1. Patentni zahtevi
1. Jedinjenje izabrano iz grupe koju čine:
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4,4-dimetilpent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(tetrahidro-2H-piran-4-il)akrilonitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(1-metilciklobutil)akrilonitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-morfolinopent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(oksetan-3-il)piperazin-1-il)pent-2-enenitril; (R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(2,2,2-trifluoretil)piperazin-1-il)pent-2-enenitril; (R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(1-metilpiperidin-4-il)pent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-ciklobutilakrilonitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-(4-(2-metoksietil)piperazin-1-il)-4-metilpent-2-enenitril; (R)-metil 4-(5-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-il)-4-cijano-2-metil-5-oksopent-3-en-2-il)piperazin-1-karboksilat;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-6-hidroksi-4-(2-hidroksietil)heks-2-enenitril;
(S)-2-(2-((4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)metil)pirolidin-1-karbonil)-4,4-dimetilpent-2-enenitril;
(S)-2-(2-((4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)metil)pirolidin-1-karbonil)-4-metil-4-(4-(oksetan-3-il)piperazin-1-il)pent-2-enenitril; (S)-2-(2-((4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)metil)pirolidin-1-karbonil)-4-metil-4-morfolinopent-2-enenitril;
(S)-metil 4-(5-(2-((4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)metil)pirolidin-1-il)-4-cijano-2-metil-5-oksopent-3-en-2-il)piperazin-1-karboksilat;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-metil-3-oksopiperazin-1-il)pent-2-enenitril; 2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-((3R,5S)-3,5-dimetilpiperazin-1-il)-4-metilpent-2-enenitril; (R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(tetrahidro-2H-tiopiran-4-il)akrilonitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(3-oksopiperazin-1-il)pent-2-enenitril;
(R)-2-(3-(4-amino-3-(4-(2,6-difluorfenoksi)fenil)-2-okso-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(oksetan-3-il)piperazin-1-il)pent-2-enenitril;
(R)-2-(3-(4-amino-3-(4-(2,3-difluorfenoksi)fenil)-2-okso-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(oksetan-3-il)piperazin-1-il)pent-2-enenitril;
(R)-2-(3-(4-amino-3-(3-fluor-4-fenoksifenil)-2-okso-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(oksetan-3-il)piperazin-1-il)pent-2-enenitril;
(R)-2-(3-(4-amino-3-(2-fluor-4-fenoksifenil)-2-okso-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(oksetan-3-il)piperazin-1-il)pent-2-enenitril;
(R)-2-(3-(4-amino-3-(3-metil-4-fenoksifenil)-2-okso-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(oksetan-3-il)piperazin-1-il)pent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-(5,6-dihidro-[1,2,4]triazolo[4,3-a]pirazin-7(8H)-il)-4-metilpent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(3-metiloksetan-3-il)piperazin-1-il)pent-2-enenitril;
1
(S)-2-(2-((4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)metil)pirolidin-1-karbonil)-4-metil-4-(4-metilpiperazin-1-il)pent-2-enenitril;
(S)-2-(2-((4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)metil)pirolidin-1-karbonil)-4-metil-4-(4-metil-3-oksopiperazin-1-il)pent-2-enenitril; (S)-2-(2-((4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)methyl)pirolidin-1-karbonil)-4-metil-4-(metil(oksetan-3-il)amino)pent-2-enonitril; (R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(4-metiltetrahidro-2H-piran-4-il)akrilonitril;
(R)-2-(3-(4-amino-3-(4-(2-fluorfenoksi)fenil)-2-okso-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(oksetan-3-il)piperazin-1-il)pent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(1-oksidotetrahidro-2H-tiopiran-4-il)akrilonitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-(4-etil-3-oksopiperazin-1-il)-4-metilpent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-ciklopropilakrilonitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(4-metil-1-(oksetan-3-il)piperidin-4-il)akrilonitril;
(R)-terc-butil 4-(5-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-il)-4-cijano-2-metil-5-oksopent-3-en-2-il)piperazin-1-karboksilat;
(R)-4-(4-acetilpiperazin-1-il)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metilpent-2-enenitril;
2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-((1R,5S)-3-oksa-8-azabiciklo[3.2.1]oktan-8-il)-4-metilpent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(1-fenilciklopropil)akrilonitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(piperazin-1-il)pent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(1-metilciklopropil)akrilonitril;
1 1
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4,4-dimetil-5-(4-metilpiperazin-1-il)-5-oksopent-2-enenitril; (R)-5-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-il)-4-cijano-N,N,2,2-tetrametil-5-oksopent-3-enamid;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4,4-dimetil-5-(4-(oksetan-3-il)piperazin-1-il)-5-oksopent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(2,2-difluciklopropil)akrilonitril;
2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-((1R,5S)-3-oksabiciklo[3.1.0]heksan-6-il)akrilonitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(6-(4-metilpiperazin-1-il)piridin-2-il)pent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(piridin-2-il)pent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-(4-(4-metilpiperazin-1-il)pirimidin-2-il)pent-2-enenitril;
(R)-4-amino-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metilpent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-(3,3-difluorpirolidin-1-il)-4-metilpent-2-enenitril;
2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-((S)-3-metoksipirolidin-1-il)-4-metilpent-2-enenitril;
2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-((R)-3-metoksipirolidin-1-il)-4-metilpent-2-enenitril;
2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-((R)-6-oksoheksahidropirolo[1,2-a]pirazin-2(1H)-il)pent-2-enenitril;
2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-((R)-2-(metoksimetil)pirolidin-1-il)-4-metilpent-2-enenitril;
1 2
2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-((S)-2-(metoksimetil)pirolidin-1-il)-4-metilpent-2-enenitril; 2-((R)-3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-4-metil-4-((S)-6-oksoheksahidropirolo[1,2-a]pirazin-2(1H)-il)pent-2-enenitril;
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(4-etiltetrahidro-2H-piran-4-il)akrilonitril; i
(R)-2-(3-(4-amino-2-okso-3-(4-fenoksifenil)-2,3-dihidro-1H-imidazo[4,5-c]piridin-1-il)piperidin-1-karbonil)-3-(4-(metoksimetil)tetrahydro-2H-piran-4-il)akrilonitril; ili farmaceutski prihvatljiva so bilo kog od prethodno navedenih jedinjenja.
2. Farmaceutska kompozicija koja obuhvata jedinjenje iz patentnog zahteva 1 i/ili njegovu farmaceutski prihvatljivu so, i farmaceutski prihvatljivi ekscipijens.
3. Jedinjenje i/ili njegova farmaceutski prihvatljiva so iz patentnog zahteva 1 za upotrebu kao lek.
4. Jedinjenje iz patentnog zahteva 1 i/ili njegova farmaceutski prihvatljiva so za upotrebu u lečenju bolesti izabrane između autoimunske bolesti, inflamatorne bolesti ili kancera kod sisara kome je to potrebno.
5. Jedinjenje i/ili njegova farmaceutski prihvatljiva so za upotrebu prema patentnom zahtevu 4, u kome je bolest akutni nekrotizirajući hemoragijski leukoencefalitis, akutni diseminovani encefalomijelitis, autoimunska bolest unutrašnjeg uha (AIED), autoimunska retinopatija, aksonalne i neuronske neuropatije, hronična inflamatorna demijelinizirajuća polineuropatija (CIDP), demijelinizirajuće neuropatije, Devikova bolest (neuromijelitis optika), eksperimentalni alergijski encefalomijelitis, arteritis džinovskih ćelija (temporalni arteritis), Giljen-Bareov sindrom, Lambert-Itonov sindrom, hronična Menijerova bolest, mijastenija gravis, neuromiotonija, opsoklonusmioklonus sindrom, optički neuritis, paraneoplastična cerebelarna degeneracija, periferna neuropatija, perivenski encefalomijelitis, sindrom nemirnih nogu, sindrom ukočene osobe, simpatička oftalmija, Takajasuov arteritis, temporalni arteritis/arteritis džinovskih ćelija, poprečni mijelitis, multipla skleroza, dizautonomija, makularna
1
degeneracija povezana sa uzrastom (vlažna i suva), transplantacija rožnjače, encefalitis, meningitis, vaskulitis ili sistemski lupus eritematozus (SLE).
6. Jedinjenje i/ili njegova farmaceutski prihvatljiva so za upotrebu prema patentnom zahtevu 4, u kome je bolest reumatoidni artritis, psorijazni artritis, lupus, uveitis, mijastenija gravis, toplokrvna autoimunska hemolitička anemija, Vegenerova granulomatoza, Sjogrenova bolest, Sjogrenovo suvo oko, bolest suvog oka koja nije Sjogrenova, psorijaza, pemfigus, urtikarija ili astma.
7. Jedinjenje i/ili njegova farmaceutski prihvatljiva so za upotrebu prema patentnom zahtevu 4, u kome je kancer difuzni limfom velikih B-ćelija, folikularni limfom, hronični limfocitni limfom, hronična limfocitna leukemija, prolimfocitna leukemija B-ćelija, limfom malih limfocita (SLL), multipli mijelom, b-ćelijski ne-Hočkinov limfom, limfoplazmocitni limfom/Valdenstremova makroglobulinemija, limfom marginalne zone slezine, mijelom plazma ćelija, plazmacitom, ekstranodalni limfom marginalne zone B-ćelija, nodalni limfom marginalne zone B-ćelija, limfom plaštnih ćelija, medijastinalni (timusni) limfom velikih B-ćelija, intravaskularni limfom velikih B-ćelija, primarni efuzioni limfom, Berkitov limfom/leukemija ili limfomatoidna granulomatoza.
Izdaje i štampa: Zavod za intelektualnu svojinu, Beograd, Kneginje Ljubice 5
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