HRP20140156T1 - Acetamidi supstituirani s n-(hetero)aril,2-(hetero)aril, koji se upotrebljavaju kao wnt-signalni modulatori - Google Patents

Acetamidi supstituirani s n-(hetero)aril,2-(hetero)aril, koji se upotrebljavaju kao wnt-signalni modulatori Download PDF

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HRP20140156T1
HRP20140156T1 HRP20140156AT HRP20140156T HRP20140156T1 HR P20140156 T1 HRP20140156 T1 HR P20140156T1 HR P20140156A T HRP20140156A T HR P20140156AT HR P20140156 T HRP20140156 T HR P20140156T HR P20140156 T1 HRP20140156 T1 HR P20140156T1
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pharmaceutically acceptable
acceptable salt
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Dai Cheng
Guobao Zhang
Dong Han
Wenqi Gao
Shifeng Pan
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Irm Llc
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Claims (19)

1. Spoj, naznačen time, da ima formulu (6): [image] ili njegova farmaceutski prihvatljiva sol, gdje: su X1, X2, X3 i X4 odabrani od N i CR7, jedan od X5, X6, X7 i X8 je N i ostali su CH, X9 je odabran od N i CH, Z je odabran od sljedećih: fenil, piranizil, piridinil, piridazinil i piperazinil; pri čemu je svaki fenil, pirazinil, piridinil, piridazinil ili piperazinil od Z opcijski supstituiran s R6-skupinom; R1, R2 i R3 su vodik; m je 1; R4 je odabran od sljedećih: vodik, halogen, difluorometil, trifluorometil i metil; R6je odabran od sljedećih: vodik, halogen i -C(O)R10, pri čemu R10 je metil; i R7 je odabran od sljedećih: vodik, halogen, cijano, metil i trifluorometil.
2. Spoj prema zahtjevu 1, naznačen time, da je taj spoj odabran od sljedećih: [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] ili njegova farmaceutski prihvatljiva sol.
3. Spoj prema zahtjevu 1, naznačen time, da taj spoj je 2-(2',3-dimetil-2,4'-bipiridin-5-il)-N-(5-(pirazin-2-il)piridin-2-il)acetamid, ili njegova farmaceutski prihvatljiva sol.
4. Spoj prema zahtjevu 1, naznačen time, da taj spoj je N-(2,3'-bipiridin-6'-il)-2-(2',3-dimetil-2,4'-bipiridin-5-il)acetamid, ili njegova farmaceutski prihvatljiva sol.
5. Spoj prema zahtjevu 1, naznačen time, da taj spoj je N-(5-(4-acetilpiperazin-1-il)piridin-2-il)-2-(2'-fluoro-3-metil-2,4'-bipiridin-5-il)acetamid, ili njegova farmaceutski prihvatljiva sol.
6. Spoj, naznačen time, da ima formulu (5): [image] ili njegova farmaceutski prihvatljiva sol, gdje: A1 je piperazinil supstituiran s -C(O)CH3, [image] ili je odabran od sljedećih: [image] prsten E je fenil ili jedan od X1, X2, X3 i X4 je N i ostali su CR7; jedan od X5, X6, X7 i X8 je N i ostali su CR11; Z je 6-člani heterocikl ili je 6-člani heteroaril, od kojih svaki sadrži 1-2 dušikovih heteroatoma i svaki od njih je opcijski supstituiran s 1-2 R6-skupine; R1, R2 i R3 su H; R4i R6su neovisno vodik, cijano, C1-6alkoksi, -S(O)2R10, -C(O)NR8R9, -1-C(O)R10, -1-C(O)OR10, C1-6alkil opcijski supstituiran sa sljedećima: halogen, C2-6alkenil ili C2-6alkinil; R5je H ili C1-6alkil; L je veza ili (CR2)1-4 gdje R je H ili C1-6alkil; W je C3-7cikloalkil; R7i R11 su neovisno H, halogen, cijano, C1-6alkoksi, -S(O)2R10 ili opcijski halogenirani C1-6alkil; R8 i R9 su neovisno H, -L-W ili C1-6alkil, C2-6alkenil ili C2-6alkinil, od kojih svaki može biti opcijski supstituiran sa sljedećima: halogen, amino, hidroksil, alkoksi ili cijano; ili R8 i R9 zajedno s atomima na koje su priključeni, mogu tvoriti prsten; R10je C1-6alkil ili -L-W; i m, n i p su neovisno 0-2.
7. Spoj prema zahtjevu 6 ili njegova farmaceutski prihvatljiva sol, naznačen(a) time, da A1 je piperazinil supstituiran s -C(O)CH3, [image] ili je odabran od sljedećih: [image] i m je 0-1.
8. Spoj prema bilo kojem od zahtjeva 6 do 7, naznačen time, da je taj spoj odabran od sljedećih: [image] [image] [image] [image] [image] [image] ili njegova farmaceutski prihvatljiva sol.
9. Spoj prema bilo kojem od zahtjeva 6 do 7, naznačen time, da je Z odabran od sljedećih: pirazinil, piridinil, piridazinil i piperazinil; pri čemu je svaki pirazinil, piridinil, piridazinil ili piperazinil od Z opcijski supstituiran s R6-skupinom.
10. Spoj prema bilo kojem od zahtjeva 1 do 9, ili njegova farmaceutski prihvatljiva sol, naznačen(a) time, da spomenuta farmaceutski prihvatljiva sol je sol fumarne kiseline toga spoja.
11. Farmaceutski sastav, naznačen time, da obuhvaća terapeutski učinkovitu količinu spoja prema bilo kojem od zahtjeva 1 do 9 ili njegovu farmaceutski prihvatljivu sol te fiziološki prihvatljiv nosač.
12. Uporaba spoja prema bilo kojem od zahtjeva 1 do 10, ili njegove farmaceutski prihvatljive soli, ili farmaceutskog sastava prema zahtjevu 11, naznačena time, da je za proizvodnju lijeka za liječenje poremećaja posredovanog putem WNT.
13. Spoj prema bilo kojem od zahtjeva 1 do 10, ili njegova farmaceutski prihvatljiva sol, naznačen(a) time, da se upotrebljava u postupku liječenja poremećaja posredovanog putem WNT.
14. Uporaba prema zahtjevu 12, ili spoj ili njegova farmaceutski prihvatljiva sol za uporabu u postupku liječenja, prema zahtjevu 13, naznačen(a) time, da je poremećaj posredovan putem WNT, sljedeći: keloidi, fibroze, proteinurija, odbacivanje bubrežnih usadaka, osteoartritis, Parkinsonova bolest, cistoidni makularni edem, retinopatija, makularna degeneracija ili stanični proliferativni poremećaj povezan sa zastranjivanjem signalnog djelovanja WNT.
15. Uporaba ili spoj ili njegova farmaceutski prihvatljiva sol, za uporabu u postupku liječenja prema zahtjevu 14, naznačen(a) time, da spomenuti poremećaj je stanični proliferativni poremećaj povezan sa zastranjivanjem signalnog djelovanja WNT, koji je odabran iz skupine koju čine kolorektalni rak, kolorektalni karcinom, rak dojke, karcinom rožnatih stanica glave i vrata, ezofagealni rak, ezofagealni karcinom rožnatih stanica, rak ne-malih stanica pluća, rak želudca, rak gušterače, leukemija, limfom, neuroblastom, retinoblastom, sarkom, osteosarkom, hondosarkom, Ewingov sarkom, rabdomiosarkom, tumor mozga, Wilmov tumor, karcinom bazalnih stanica, melanom, rak glave i vrata, cervikalni rak i rak prostate.
16. Uporaba spoja prema bilo kojem od zahtjeva 1 do 10, ili njegove farmaceutski prihvatljive soli ili farmaceutskog sastava prema zahtjevu 11, naznačena time, da je za proizvodnju lijeka za liječenje poremećaja koji se može liječiti inhibicijom signalizacije WNT.
17. Spoj prema bilo kojem od zahtjeva 1 do 10, ili njegova farmaceutski prihvatljiva sol, naznačen(a) time, da se upotrebljava u postupku liječenja poremećaja koji se može liječiti inhibicijom signalizacije WNT.
18. Uporaba spoja prema bilo kojem od zahtjeva 1 do 10, ili njegove farmaceutski prihvatljive soli ili farmaceutskog sastava prema zahtjevu 11, naznačena time, da je za proizvodnju lijeka za liječenje poremećaja koji se može liječiti inhibicijom Porcupine-gena.
19. Spoj prema bilo kojem od zahtjeva 1 do 10, ili njegova farmaceutski prihvatljiva sol, naznačen(a) time, da se upotrebljava u postupku liječenja poremećaja koji se može liječiti inhibicijom Porcupine-gena.
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UA103918C2 (en) 2013-12-10
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CN102731379A (zh) 2012-10-17
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KR20110122870A (ko) 2011-11-11
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