HRP20220195T1 - Novi spojevi sulfonamid karboksamida - Google Patents

Novi spojevi sulfonamid karboksamida Download PDF

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HRP20220195T1
HRP20220195T1 HRP20220195TT HRP20220195T HRP20220195T1 HR P20220195 T1 HRP20220195 T1 HR P20220195T1 HR P20220195T T HRP20220195T T HR P20220195TT HR P20220195 T HRP20220195 T HR P20220195T HR P20220195 T1 HRP20220195 T1 HR P20220195T1
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Croatia
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image
disease
compound according
independently selected
group
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HRP20220195TT
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Inventor
Matthew Cooper
David Miller
Angus Macleod
Jimmy Van Wiltenburg
Stephen Thom
Stephen St-Gallay
Jonathan Shannon
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Inflazome Limited
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Priority claimed from GBGB1710943.0A external-priority patent/GB201710943D0/en
Priority claimed from GBGB1713082.4A external-priority patent/GB201713082D0/en
Priority claimed from GBGB1713079.0A external-priority patent/GB201713079D0/en
Priority claimed from GBGB1718561.2A external-priority patent/GB201718561D0/en
Priority claimed from GBGB1718563.8A external-priority patent/GB201718563D0/en
Priority claimed from GBGB1721726.6A external-priority patent/GB201721726D0/en
Application filed by Inflazome Limited filed Critical Inflazome Limited
Publication of HRP20220195T1 publication Critical patent/HRP20220195T1/hr

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    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4465—Non condensed piperidines, e.g. piperocaine only substituted in position 4
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Claims (20)

1. Spoj forume (I): [image] pri čemu: Q je O; R1 je nearomatska heterociklična skupina odabrana od: [image] pri čemu je R1 pričvršćen na atom sumpora u skupini sumpora pomoću atoma prstenastog ugljika, pri čemu se R1 može se po želji zamijeniti jednim ili više supstituenata neovisno odabranih iz halo; -CN; -NO2; -N3; -Rβ; -OH; -ORβ; -SH; -SRβ; -SO2Rβ; -NH2; -NHRβ; -N(Rβ)2; -CHO; -CORβ; -COOH; -COORβ; -OCORβ; -Rα-CHO; -Rα-CORβ; -Rα-COOH; -Rα-COORβ; -Rα-OCORβ; -NH-CHO; -NRβ-CHO; -NH-CORβ; -NRβ-CORβ; -CONH2; -CONHRβ; -CON(Rβ)2; -Rα-NH-CHO; -Rα-NRβ-CHO; -Rα-NH-CORβ; -Rα-NRβ-CORβ; -Rα-CONH2; -Rα-CONHRβ; -Rα-CON(Rβ)2; C3-C7 cikloalkilna skupina po želji zamijenjena jednom ili više C1-C3 alkil ili C1-C3 haloalkilnima skupinama; C3-C7 cikloalkenilna skupina po želji zamijenjena jednom ili više C1-C3 alkil ili C1-C3 haloalkilnim skupinama; [image] ; okso (=O); ili C1-C4 alkilenski most; svaki -Rα- se neovisno odabire iz skupine alkilena, alkenilena ili alkinilena, pri čemu skupina alkilena, alkenilena ili alkinylena sadrži od 1 do 6 atoma ugljika u kralježnici, pri čemu se skupina alkilen, alkenilen ili alkinylen može po želji zamijeniti jednom ili više aureola i/ili -Rβ grupama; svaki -Rβ neovisno je odabrana iz C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil ili C2-C6 cikličke skupine, pri čemu bilo koja -Rβ može se po želji zamijeniti jednom ili više C1-C3 alkil, C1-C3 haloalkil, C3-C7 cikloalkil, -O(C1-C3 alkil), halo, -CN, -C≡CH ili okso (=O) skupinama; svaki -Rδ neovisno je odabraa iz C1-C6 alkil ili C1-C3 haloalkilne skupine; svaki m je neovisno odabran iz 1, 2 ili 3; svaki n je neovisno odabran iz 1, 2 ili 3; i R2 je: [image]
2. Složeni spoj sukladno zahtjevu 1, pri čemu R1 zamjenjuje se jednim ili više potpostituenta neovisno odabranih iz halo; -CN; -N3; -Rβ; -SO2Rβ; -NH2; -NHRβ; -N(Rβ)2; -CHO; -CORβ; -COORβ; -OCORβ; -Rα-CHO; -Rα-CORβ; -Rα-COORβ; -Rα-OCORβ; -NH-CHO; -NRβ-CHO; -NH-CORβ; -NRβ-CORβ; -CONH2; -CONHRβ; -CON(Rβ)2; [image] ; ili okso (=O); pri čemu: svaki -Rα- neovisno je odabran iz C1-C3 alkilenske skupine; svaki -Rβ neovisno je odabrana iz C1-C6 alkil ili C3-C6 cikloalkilne skupine, i u kojem bilo koji -Rβ može se po želji zamijeniti jednim ili više C3-C6 cikloalkila, -O(C1-C3 alkil), halo, -CN or -C≡CH grupama; svaki -Rδ neovisno je odabran iz C1-C6 alkilne skupine; svaki m je neovisno odabran iz 1 ili 2; i svaki n je neovisno odabran iz 1 ili 2.
3. Složeni spoj sukladno zahtjevu 1, pri čemu R1 zamjenjuje atom dušika u prstenu sa substituentom odabranom iz halo; C1-C6 alkil; C1-C6 haloalkil; C2-C6 alkenil; C2-C6 haloalkenil; C2-C6 alkinil; C2-C6 haloalkinil; -R5-CN; -R5-COR6; -R5-COOR6; -R5-CON(R6)2; -R5-(C3-C6 cikloalkil); [image] ; okso (=O); -CH2CH2CH2-; ili -CH2CH2CH2CH2-; pri čemu: R5 neovisno se odabire iz veze ili C1-C5 alkilena; R6 samostalno odabire iz vodika, C1-C5 alkila, C1-C5 haloalkila ili C3-C6 cikloalkila; m je 1, 2 ili 3; i n je 1, 2 ili 3.
4. Složeni spoj sukladno bilo kojem od zahtjeva 1 do 3, pri čemu R1 je monociklička nearomatska heterociklička skupina odabrana iz: [image] pri čemu R1 pričvršćuje se na atom sumpora u skupini sumpora pomoću atoma prstenastog ugljika, pri čemu se R1 može se po želji zamijeniti kako je definirano u bilo kojem od zahtjeva od 1 do 3.
5. Složeni spoj sukladno bilo kojem od zahtjeva 1 do 4, pri čemu R1 zamjenjuje se atomom dušika u prstenu substituentom kako je definirano u bilo kojem od zahtjeva od 1 do 3.
6. Složeni spoj sukladno bilo kojem od zahtjeva od 1 do 5, odabran iz skupine koja se sastoji od: [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]
7. Složeni spoj sukladno bilo kojem od zahtjeva od 1 do 6, pri čemu je spoj: [image]
8. Složeni spoj sukladno bilo kojem od zahtjeva od 1 do 6, pri čemu je spoj: [image]
9. Složeni spoj sukladno bilo kojem od zahtjeva od 1 do 6, pri čemu je spoj: [image]
10. Složeni spoj sukladno bilo kojem od zahtjeva od 1 do 6, pri čemu je spoj: [image]
11. Farmaceutski prihvatljiva sol ili solvat spoja sukladno bilo kojem od zahtjeva od 1 do 6.
12. Farmaceutski prihvatljiva sol ili solvat spoja sukladno zahtjevu 7.
13. Farmaceutski prihvatljiva sol ili solvat spoja sukladno zahtjevu 8.
14. Farmaceutski prihvatljiva sol ili solvat spoja sukladno zahtjevu 9.
15. Farmaceutski prihvatljiva sol ili solvat spoja sukladno zahtjevu 10.
16. Farmaceutski pripravak koji se sastoji od spoja sukladno kojem od zahtjeva od 1 do 10, ili farmaceutski prihvatljive soli ili solvata sukladno kojem od zahtjeva od 11 do 15, i farmaceutski prihvatljive pomoćne tvari.
17. Spoj sukladno kojem od zahtjeva od 1 do 10 ili farmaceutski prihvatljiva sol ili solvat sukladno kojem od zahtjeva od 11 do 15 ili farmaceutski pripravak sukladno zahtjevu 16, za primjenu u medicini.
18. Spoj, farmaceutski prihvatljiva sol, solvat ili farmaceutski pripravak sukladno zahtjevu 17, za uporabu u liječenju ili prevenciji bolesti, poremećaja ili stanja, pri čemu je bolest, poremećaj ili stanje odabrano od sljedećeg: (i) upala; (ii) autoimuna bolest; (iii) rak; (iv) infekcija; (v) bolest središnjeg živčanog sustava; (vi) metabolička bolest; (vii) kardiovaskularna bolest; (viii) respiratorna bolest; (ix) bolest jetre; (x) bubrežna bolest; (xi) očna bolest; (xii) kožna bolest; (xiii) poremećaj limfe; (xiv) psihološki poremećaj; (xv) bolest presatka protiv domaćina; i (xvi) alodinija.
19. Spoj, farmaceutski prihvatljiva sol, solvat ili farmaceutski pripravak sukladno zahtjevu 17, za uporabu u liječenju ili prevenciji bolesti, poremećaja ili stanja, pri čemu je bolest, poremećaj ili stanje odabrano od sljedećeg: (i) periodični sindromi povezani s kriopirinom (CAPS); (ii) Muckle-Wells sindrom (MWS); (iii) obiteljski autoupalni sindrom hladnoće (FCAS); (iv) multisistemska upalna bolest novorođenčadi (NOMID); (v) obiteljska mediteranska groznica (FMF); (vi) piogeni artritis, pyoderma gangrenosum i sindrom akni (PAPA); (vii) hiperimunoglobulinemija D i sindrom periodične groznice (HIDS); (viii) periodični sindrom povezan s faktorom nekroze tumora (TNF) receptorom (TRAPS); (ix) sistemski juvenilni idiopatski artritis; (x) Stillova bolest s početkom u odraslih (AOSD); (xi) relapsirajući polihondritis; (xii) Schnitzlerov sindrom; (xiii) Sweetov sindrom; (xiv) Behcetova bolest; (xv) anti-sintetazni sindrom; (xvi) nedostatak antagonista receptora interleukina 1 (DIRA); i (xvii) haploinsuficijencija A20 (HA20).
20. Ex vivo ili in vitro metoda inhibicije NLRP3, metoda koja obuhvaća uporabu spoja sukladno bilo kojem od zahtjeva 1 do 10, ili farmaceutski prihvatljiva sol ili solvat sukladno bilo kojem od zahtjeva 11 do 15, ili farmaceutski pripravak sukladno zahtjevu 16, za inhibiranje NLRP3.
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