ME02857B - Triazolopirazini kao brd4 inhibitori za primenu u lečenju karcinoma - Google Patents

Triazolopirazini kao brd4 inhibitori za primenu u lečenju karcinoma

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Publication number
ME02857B
ME02857B MEP-2017-190A MEP2017190A ME02857B ME 02857 B ME02857 B ME 02857B ME P2017190 A MEP2017190 A ME P2017190A ME 02857 B ME02857 B ME 02857B
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iii
compound
optionally
compound according
3alkyl
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MEP-2017-190A
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German (de)
English (en)
French (fr)
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Harald Engelhardt
Christian Smethurst
Davide Gianni
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Boehringer Ingelheim Int
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Publication of ME02857B publication Critical patent/ME02857B/me

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Claims (33)

1. Jedinjenje formule (I) u kojoj, R1 je -C1-3alkil ili -C1-3haloalkil; R2 je odabran od -NHR4, -C1-5alkil, -C1-5haloalkil, halogen i -S-C1-3alkil; R3 je 5-12 člani heteroaril, na kome je grupa supstituisana sa -X-R10 i opciono dalje supstituisana sa jednom ili više grupa nezavisno odabranih od R9; R4 je odabran od -C1-5alkil i 5-12 članog heterocikloalkila, gdje heterocikloalkil može biti opciono sustituisan sa jednom ili više grupa nezavisno odabranih od R5; R5 je odabran od -C1-5alkil, -C1-5haloalkil i -C1-3alkilen-O-C1-3alkil; R9 je odabran od -C1-5alkil, -O-C1-5alkil, -N(C1-5alkil)2, halogen, -C1-3alkilen-O-C1-3alkil, -C1-5alkilen-N(-C1-5alkil, -C1-5alkil), 5-12 članog heterocikloalkila, u kome heterocikloalkil grupa može biti opciono sustituisana sa jednom ili više grupa nezavisno odabranih od =O, ‑C1-3alkil, ili R9 je odabran od -C6-10aril i 5-12 članog heteroarila, u kome aril i heteroaril grupe mogu biti opciono i nezavisno supstituisane sa jednom ili više grupa odabranih od halogen, -C1-3alkil, -O-C1-3alkil, -C1-3haloalkil, -O-C1-3haloalkil, -N(C1-5alkil, C1-5alkil) i -NH-C1-5alkil; X je -C1-3alkilen- ili -O-; R10 je -C6-10aril ili 5-12 člani heteroaril, gdje svaka od grupa može biti opciono sustituisana sa jednom ili više grupa odabranih od halogen, -C1-3alkil, -O-C1-3alkil, -C1-3haloalkil, -O-C1-3haloalkil; u kojoj jedinjenja formule (I) mogu biti opciono prisutne u obliku soli.
2. Jedinjenje prema zahtjevu 1, u kome R1 je -CH3.
3. Jedinjenje prema zahtjevu 1 ili 2, u kome R2 je -NHR4 i R4 je 5-6 člani heterocikloalkil, opciono supstituisan kako je definisano u zahtjevu 1.
4. Jedinjenje prema zahtjevu 3, u kome R4 je tetrahidrofuran ili piperidin, u kome je piperidin supstituisan sa jednom grupom odabranom od -CH3, -CH2CH3, -CH2CH2CH3 i -(CH2)2-O-CH3.
5. Jedinjenje prema bilo kom od zahteva 1 ili 2, u kome R2 je -NHR4 i R4 je -C1-3alkil.
6. Jedinjenje prema zahtjevu 5, u kome R2 je -NHR4 i R4 je -CH3 ili -CH(CH3)2.
7. Jedinjenje prema bilo kom od zahtjeva 1 ili 2, u kome R2 je -C1-3alkil.
8. Jedinjenje prema bilo kom od zahtjeva 1 do 7, u kome R3 je 5-9 člani heteroaril supstituisan sa -X-R10 i opciono dalje supstituisan sa jednom ili više grupa nezavisno odabranih od R9, u kome R9, X i R10 su definisani kao u zahtjevu 1.
9. Jedinjenje prema bilo kom od zahtjeva 1 do 8, u kome -X-R10 je odabran od -CH2-fenil, -CH(CH3)-fenil, -CH2-piridil, -CH(CH3)-piridil, -O-fenil, od kojih svaka fenil ili piridil grupa je opciono supstituisana sa –F ili ‑CH3.
10. Jedinjenje prema zahtjevu 9, u kome -X-R10 je odabran od -CH2-fenil, -CH2-piridil, -CH(CH3)-fenil, -CH(CH3)-piridil, od kojih svaka piridil ili fenil grupa je opciono supstituisana sa –F ili –CH3.
11. Jedinjenje prema zahtjevu 8, u kome R3 je odabran od pirazolil, imidazol, benzimidazolil, imidazopiridin i imidazopirimidin i R3 supstituisan sa -X-R10 i R3 je opciono dalje supstituisan sa jednom ili više grupa nezavisno odabranih od R9 u kome R9, X i R10 su definisani kao u zahtjevu 1.
12. Jedinjenje prema bilo kom od zahtjeva 1 do 11, u kome R9 je nezavisno odabran od -C1-3alkil, -O-C1-3alkil, -N(C1-3alkil)2, fenil i 6 člani heterocikloalkil, gdje heterocikloalkil može biti opciono sustituisan sa jednom ili više grupa nezavisno odabranih od =O i -C1-3alkil.
13. Jedinjenje prema zahtjevu 11, u kome R3 je imidazopiridin ili benzimidazol supstituisan sa -CH2-fenil ili -CH(CH3)-piridil i opciono dalje supstituisan sa -C1-3alkil ili 5-12 člani heterocikloalkil u kome heterocikloalkil grupa može biti opciono sustituisana sa jednom ili više grupa nezavisno odabranih od -C1-3alkil.
14. Jedinjenje prema zahtjevu 13, u kome R3 je imidazopiridin ili benzimidazol supstituisan sa -CH2-fenil, -CH(CH3)-piridil ili -CH2-piridil i sa -CH(CH3 )2 ili morfolinil ili piperazinil, u kome je morfolinil ili piperazinil grupa opciono supstituisana sa jednom ili više grupa odabranih od -C1-3alkil.
15. Jedinjenje prema zahtjevu 1 odabrano od EKS# Struktura Eks # Struktura I-1 I-2 I-3 I-4 I-5 II-1 II-2 II-3 III-1 III-2 III-3 III-4 III-5 III-6 III-7 III-8 III-9 III-10 III-11 III-12 III-13 III-14 III-15 III-16 III-17 III-18 III-19 III-20 III-21 III-22 III-23 III-24 III-25 III-26 III-27 III-28 III-29 III-30 III-31 III-32 III-33 III-34 III-35 III-36 III-37 III-38 III-39 III-40 III-41 III-42 III-43 III-44 III- 45 III-46 III-47 III-48 III-49 III-50 III-51 III-52 III-53 u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
16. Jedinjenje prema zahtjevu 1 ili 15 (III-13), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
17. Jedinjenje prema zahtjevu 1 ili 15 (III-8), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
18. Jedinjenje prema zahtjevu 1 ili 15 (III-40), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
19. Jedinjenje prema zahtjevu 1 ili 15 (III-26), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
20. Jedinjenje prema zahtjevu 1 ili 15 (III-19), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
21.Jedinjenje prema zahtjevu 1 ili 15 (III-30), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
22.Jedinjenje prema zahtjevu 1 ili 15 (III-20), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
23.Jedinjenje prema zahtjevu 1 ili 15 (III-21), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
24.Jedinjenje prema zahtjevu 1 ili 15 (III-1), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
25.Jedinjenje prema zahtjevu 1 ili 15 (III-27), , u kome jedinjenje može biti opciono prisutno u obliku njegove soli.
26. Jedinjenje opšte formule (I) prema bilo kom od zahtjeva 1 do 25 - ili njegova farmaceutski prihvatljiva so - za primenu u liječenju i/ili prevenciji karcinoma.
27. Jedinjenje opšte formule (I) prema bilo kom od zahtjeva 1 do 26 ili njegova so u obliku hidrata, solvata ili polimorfa.
28. Farmaceutski preparat koji kao aktivnu supstancu sadrži jedno ili više jedinjenja opšte formule (I) prema bilo kom od zahtjeva 1 do 25 opciono u kombinaciji sa konvencionalnim ekscipijentima i/ili nosačima.
29. Farmaceutski preparat koji obuhvata jedinjenje opšte formule (I) prema bilo kom od zahtjeva 1 do 25 - ili jednu od njegovih farmaceutski prihvatljivih soli - i najmanje još jednu citostatičnu ili citotoksičnu supstancu, drugačiju od formule (I).
30. Jedinjenje opšte formule (I) prema bilo kom od zahtjeva 1 do 25 - ili njegove farmaceutski prihvatljive soli - za primjenu kao medikamenti.
31. Jedinjenje opšte formule (I) prema bilo kom od zahtjeva 1 do 25 - ili njegove farmaceutski prihvatljive soli - za primjenu u liječenju hematopoetskih maligniteta.
32. Jedinjenje opšte formule (I) prema bilo kom od zahtjeva 1 do 25 - ili njegove farmaceutski prihvatljive soli - za primjenu u liječenju akutne mijeloidne leukemije ili multiplog mijeloma.
33. Jedinjenje opšte formule (I) prema bilo kom od zahtjeva 1 do 25 - ili njegove farmaceutski prihvatljive soli - za primjenu u liječenju karcinoma pluća, jetre, debelog creva, mozga, štitne žlezde, pankreasa, dojke, jajnika i prostate.
MEP-2017-190A 2012-11-16 2013-11-15 Triazolopirazini kao brd4 inhibitori za primenu u lečenju karcinoma ME02857B (me)

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