HRP20201621T1 - Derivati indola za uporabu u medicini - Google Patents

Derivati indola za uporabu u medicini Download PDF

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Publication number
HRP20201621T1
HRP20201621T1 HRP20201621TT HRP20201621T HRP20201621T1 HR P20201621 T1 HRP20201621 T1 HR P20201621T1 HR P20201621T T HRP20201621T T HR P20201621TT HR P20201621 T HRP20201621 T HR P20201621T HR P20201621 T1 HRP20201621 T1 HR P20201621T1
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Croatia
Prior art keywords
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cancer
lymphoma
leukemia
cell
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HRP20201621TT
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English (en)
Inventor
Phillip Cowley
Alan Wise
Susan Davis
Michael Kiczun
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Iomet Pharma Ltd.
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Priority claimed from GB201406154A external-priority patent/GB201406154D0/en
Priority claimed from GB201502156A external-priority patent/GB201502156D0/en
Application filed by Iomet Pharma Ltd. filed Critical Iomet Pharma Ltd.
Publication of HRP20201621T1 publication Critical patent/HRP20201621T1/hr

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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
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    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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Claims (8)

1. Spoj za uporabu u liječenju raka, spoj koji uključuje slijedeću formulu: [image] - R1, R3 i R4 se, svaki neovisno, biraju između H i F; - R2 se bira između -Cl, -Br, -CN, -OMe i -OEt; - R7 je H; - R5 i R61 se neovisno biraju između H i C1-C6 alkil; - R65 se bira između supstituirane ili nesupstituirane fenil grupe, supstituirane ili nesupstituirane pirazol-4-il grupe, supstituirane ili nesupstituirane oksazol-4-il grupe i supstituirane ili nesupstituirane izoksazol-3-il grupe; i - R63 i R64 se biraju iz grupe u kojoj R63 i R64 zajedno formiraju 3-6-člani karbociklični ili heterociklični prsten odabran između ciklopropil, ciklobutil, ciklopentil, ciklopentenil, cikloheksil, cikloheksenil, aziridin, azetidin, pirolidin, piperidin, piperazin, oksetan, tetrahidrofuran i tetrahidropiran prstena.
2. Spoj za uporabu prema patentnom zahtjevu 1, naznačen time, što spoj uključuje spoj koje se bira između jednog od slijedećih: [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image]
3. Spoj za uporabu prema patentnom zahtjevu 1 ili patentnom zahtjevu 2, naznačen time, što je spoj inhibitor IDO, a rak je poželjno rak odabran između: čvrstog ili tekućeg tumora uključujući rak oka, mozga (na primjer gliom, glioblastom, meduloblastom, kraniofaringeom, ependimom i astrocitom), leđne moždine, bubrega, usta, usne, grla, usne šupljine, nosne šupljine, tankog crijeva, debelog crijeva, paratiroidne žlijezde, žučnog mjehura, glave i vrata, dojke, kosti, žučnog kanala, vrata maternice, srca, hipofaringealne žlijezde, pluća, bronha, jetre, kože, mokraćovoda, uretre, testisa, vagine, anusa, laringealne žlijezde, jajnika, tiroidne žlijezde, ezofagusa, nazofaringealne žlijezde, hipofize, slinovnice, prostate, gušterače, nadbubrežnih žlijezdi; rak endometrija, rak usne šupljine, melanom, neuroblastom, rak želuca, angiomatozu, hemangioblastom, feohromocitom, ciste gušterače, raka bubrežnih stanica, Wilmsov tumor, rak pločastih stanica, sarkom, osteosarkom, Kaposijev sarkom, rabdomiosarkom, hepatocelularni rak, PTEN hemartomske tumorske sindrome (PHTS) (na primjer Lhermitte-Duclos bolest, Cowdenov sindrom, Proteus sindrom, i Proteusu sličan sindrom), leukemije i limfome (kao što su akutna limfoblastna leukemija, kronična limfocitna leukemija, akutna mijelogena leukemija, kronična mijelogena leukemija, leukemija dlakavih stanica, prolimfocitna leukemija T-stanica (T-PLL), leukemija velikih granularnih limfocita, leukemija T-stanica u odrasloj dobi, juvenilna mijelomonocitna leukemija, Hodgkinov limfom, ne-Hodgkinov limfom, limfom plašta, folikularni limfom, primarni izlivni limfom, limfom povezan sa AIDS, Hodgkinov limfom, difuzni limfom B stanica, Burkittov limfom i limfom T-stanica kože), poželjno pri čemu se rak bira između akutne mijeloidne leukemije (AML), sitnostaničnog raka pluća, melanoma, raka jajnika, kolorektalnog raka, raka gušterače, raka endometrija i papiloma kože.
4. Spoj za uporabu prema patentnom zahtjevu 1 ili patentnom zahtjevu 2, naznačen time, što je spoj inhibitor TDO i rak je rak odabran između: čvrstog ili tekućeg tumora uključujući rak oka, mozga (na primjer gliom, glioblastom, meduloblastom, kraniofaringeom, ependimom i astrocitom), leđne moždine, bubrega, usta, usne, grla, usne šupljine, nosne šupljine, tankog crijeva, debelog crijeva, paratiroidne žlijezde, žučnog mjehura, glave i vrata, dojke, kosti, žučnog kanala, vrata maternice, srca, hipofaringealne žlijezde, pluća, bronha, jetre, kože, mokraćovoda, uretre, testisa, vagine, anusa, laringealne žlijezde, jajnika, tiroidne žlijezde, ezofagusa, nazofaringealne žlijezde, hipofize, slinovnice, prostate, gušterače, nadbubrežnih žlijezdi; rak endometrija, rak usne šupljine, melanom, neuroblastom, rak želuca, angiomatozu, hemangioblastom, feohromocitom, cista gušterače, rak bubrežnih stanica, Wilmsov tumor, rak skvamoznih stanica, sarkom, osteosarkom, Kaposijev sarkom, rabdomiosarkom, hepatocelularni rak, PTEN hemartomske tumorske sindrome (PHTS) (na primjer Lhermitte-Duclos bolest, Cowdenov sindrom, Proteus sindrom, i Proteusu sličan sindrom), leukemije i limfome (kao što su akutna limfoblastna leukemija, kronična limfocitna leukemija, akutna mijelogena leukemija, kronična mijelogena leukemija, leukemija dlakavih stanica, prolimfocitna leukemija T-stanica (T-PLL), leukemija velikih granularnih limfocita, leukemija T-stanica u odrasloj dobi, juvenilna mijelomonocitna leukemija, Hodgkinov limfom, ne-Hodgkinov limfom, limfom plašta, folikularni limfom, primarni izlivni limfom, limfom povezan sa AIDS, Hodgkinov limfom, difuzni limfom B stanica, Burkittov limfom i limfom T-stanica kože), poželjno pri čemu je rak odabran između glioma i hepatocelularnog raka.
5. Spoj koje je spoj bilo koje od slijedećih formula: [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image]
6. Farmaceutski pripravak, naznačen time, što sadrži spoj definiran u patentnom zahtjevu 5 i sadrži još i farmaceutski prihvatljivi aditiv i/ili ekscipijent, i/ili gdje je spoj u obliku farmaceutski prihvatljive soli.
7. Farmaceutski pripravak prema patentnom zahtjevu 6 za uporabu u liječenju raka, koji sadrži još i dodatno sredstvo za liječenje raka; poželjno pri čemu se dodatno sredstvo za liječenje raka bira između antimikrotubularnih sredstava, koordinacijskih kompleksa platine, alkilirajućih sredstava, antibiotskih sredstava, inhibitora topoizomeraze II, antimetabolita, inhibitora topoizomeraze I, hormona i analoga hormona, inhibitora puta za prijenos signala, nereceptorskih tirozin kinaznih inhibitora angiogeneze, imunoterapijskih sredstava (kao što su antitumorsko cjepivo, onkolitički virus, imunostimulatorno antitijelo, na primjer anti-CTLA4, anti-PDl, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-anti-CD40, anti-LAG3, anti-TIM3 i anti-GITR, novi dodatak, peptid, citokin, terapija T stanicama sa himernim antigenskim receptorom (CAR-T), imunski modulator sa malom molekulom, modulator tumorskog mikrookruženja i antiangiogena sredstva), proapoptotskih sredstava i inhibitora signalizacije unutar staničnog ciklusa.
8. Farmaceutski pripravak za uporabu prema patentnom zahtjevu 7, naznačen time, što uključuje još i sredstvo koje se bira između: antitumorskog cjepiva; imunoterapijskog liječenja raka (kao što je modulator imunološke kontrolne točke, na primjer anti-CTLA4, anti-PDl, anti PDL-1, anti-LAG3, ili anti-TIM3 sredstvo, i OX40, 41BB ili GITR agonisti); terapije citokinima i terapije T stanicama sa himernim antigenskim receptorom (CAR-T).
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