HRP20131041T1 - 6-supstituirani izokinolini i izokinolinoni - Google Patents

6-supstituirani izokinolini i izokinolinoni Download PDF

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HRP20131041T1
HRP20131041T1 HRP20131041AT HRP20131041T HRP20131041T1 HR P20131041 T1 HRP20131041 T1 HR P20131041T1 HR P20131041A T HRP20131041A T HR P20131041AT HR P20131041 T HRP20131041 T HR P20131041T HR P20131041 T1 HRP20131041 T1 HR P20131041T1
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alkyl
isoquinolin
alkylene
chloro
cis
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HRP20131041AT
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Oliver Plettenburg
Katrin Lorenz
Matthias Loehn
John Weston
Heinz-Werner Kleemann
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Sanofi
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Claims (50)

1. Spoj formule (I) [image] , naznačen time što R1 je H, OH ili NH2; R3 je H, halogen, CN, (C1-C6) alkil, OH, NH2 ili NHR′; R4 je H, halogen, hidroksi, CN, (C1-C6) alkil, R′ ili (C1-C6) alkilen-R′; R5 je H, halogen, CN, (C1-C6) alkil ili R′; R7 je H, halogen, CN, (C1-C6) alkil, O-(C1-C6) alkil, R′ ili SO2-NH2; R8 je H, halogen ili (C1-C6) alkil; R9 je R′, OH, halogen, (C1-C6) alkil, O-(C1-C6) alkil, (C1-C6) alkilen-R′, (C2-C6) alkenil, (C2-C6) alkinil, (C1-C6) alkilen-O-R′, (C1-C6) alkilen-CH[R′]2, (C1-C6) alkilen-C(O)-R′, (C1-C6) alkilen-C(O)NH2, (C1-C6) alkilen-C(O)NH-R′, (C1-C6) alkilen-C(O)NH-(C1-C6) alkil, (C1-C6) alkilen-C(O)N[(C1-C6) alkil]2, (C1-C6) alkilen-C(O)N[R′]2; (C1-C6) alkilen-C(O)O-(C1-C6) alkil, COOH, C(O)O-(C1-C6) alkil, C(O)OR′ C(O)(C1-C6) alkil, C(O)R′, C(O)NH2, C(O)-NH-(C2-C6) alkenil, C(O)-NH-(C2-C6) alkinil, C(O)NH-(C1-C6) alkil, C(O)NHR′, C(O)-NH(C1-C6) alkilen-R′, C(O)N[(C1-C6) alkil]R′ C(O)N[(C1-C6) alkil]2, C(O)-(C1-C6) alkilen-R′ ili C(O)O(C1-C6) alkilen-R′; R6 je odsutan; ili je jedan (C1-C4) alkilen, vezan na cikloalkilni prsten, gdje (C1-C4) alkilen tvori drugu vezu s različitim atomom ugljika u cikloalkilnom prstenu kako bi tvorio biciklički sustav prstena, gdje su u bicikličkom sustavu prstena izborno jedan ili dva atoma ugljika zamijenjeni skupinom koju se neovisno bira između O, N-R15, S, SO ili SO2; ili, ako su m i s 2, m je 3, a s je 1, ili m je 4, a s je 0, R6 je CH2-CH-(CH2)2, koji je vezan s jednim CH2 na cikloalkilni prsten i the druga dva CH2 su vezana na različite atome ugljika u cikloalkilnom prstenu; i, ako je m 3, a s je 3, R6 su dvije metilenske skupine, vezane na različite atome ugljika u cikloalkilnom prstenu, gdje su metilenske skupine ili skupina CH2-CH-(CH2)2 tako vezani na atome ugljika u cikloalkilnom prstenu da tvore adamantanski sustav formule [image] , gdje L može biti vezan na bilo koji sekundarni ili tercijarni atom ugljika i gdje biciklički sustav prstena ili adamantanski sustav nije supstituiran ili je izborno supstituiran s R9, R10 je (C1-C6) alkil, (C1-C8) heteroalkil, (C3-C8) cikloalkil, (C3-C8) heterocikloalkil, (C1-C6) alkilen-(C3-C8) cikloalkil, (C1-C6) alkilen-(C6-C10) aril, (C1-C6) alkilen-(C5-C10) heteroaril, (C1-C6) alkilen-(C3-C8) heterocikloalkil, C(O)NH-(C1-C6) alkil, C(O)N[(C1-C6) alkil]2, C(O)NH-R′, C(O)N-((C1-C6) alkil)-R′ ili C(O)NH-(C1-C6) alkilen-R′; R11 je H, (C1-C6) alkil, (C1-C6) alkilen-R′, R′, ili R11 i R12, zajedno s atomom ugljika na kojeg su vezani, tvore (C3-C8) cikloalkilni ili (C3-C8) heterocikloalkilni prsten; R12 je (C1-C6) alkil, (C3-C8) cikloalkil, (C5-C10) heteroaril, (C3-C8) heterocikloalkil ili (C6-C10) aril; ili R12 je H, uz uvjet da r = 2, a drugi R12 nije H; ili R11 i R12, zajedno s atomom ugljika na kojeg su vezani, tvore (C3-C8) cikloalkilni ili (C3-C8) heterocikloalkilni prsten; R13 i R14 su međusobno neovisno H, R′, (C1-C6) alkil, (C1-C6) alkilen-R′, (C1-C6) alkilen-O-(C1-C6) alkil, (C1-C6) alkilen-O-R′, (C1-C6) alkilen-CH[R′]2, (C1-C6) alkilen-C(O)-R′, (C1-C6) alkilen-C(O)NH2, (C1-C6) alkilen-C(O)NH-R′, (C1-C6) alkilen-C(O)NH-(C1-C6) alkil, (C1-C6) alkilen-C(O)N[(C1-C2) alkil]2, (C1-C6) alkilen-C(O)N[R′]2, (C1-C6) alkilen-C(O)O-(C1-C6) alkil, C(O)O-(C1-C6) alkil, C(O)OR′, C(O)(C1-C6) alkil, C(O)R′, C(O)NH-(C1-C6) alkil, C(O)NHR′, C(O)N[(C1-C6) alkilR′ C(O)N[(C1-C6) alkil]2, C(O)-(C1-C6) alkilen-R′, C(O)O(C1-C6) alkilen-R′, ili R13 i R14, zajedno s N atomom na kojeg su vezani, tvore (C3-C8) heterocikloalkil; R15 je H ili (C1-C6) alkil; n je 0, 1, 2, 3 ili 4; m je 1, 2, 3 ili 4; s je 0, 1, 2 ili 3; r je 1 ili 2; L je O(CH2)p, S(CH2)p, S(O)(CH2)p, SO2(CH2)p, NH(CH2)p, N(C1-C6) alkil-(CH2)p, N(C3-C6) cikloalkil-(CH2)p ili N[(C1-C3) alkilen-R′]-(CH2)p; p je 0, 1, 2, 3 ili 4; R′ je (C3-C8) cikloalkil, (C5-C10) heteroaril, (C3-C8) heterocikloalkil, (C6-C10) aril; gdje u ostacima R3 do R15 alkil ili alkilen nije supstituiran ili je izborno jednom ili više puta supstituiran s OH, OCH3, C(O)OH, C(O)OCH3, NH2, NHCH3, N(CH3)2, C(O)NH2, C(O)NHCH3 ili C(O)N(CH3)2; gdje u ostacima R3 do R15 cikloalkil ili heterocikloalkil nije supstituiran ili je izborno jednom ili više puta supstituiran s (C1-C6) alkilom, halogenom, OH, OCH3, C(O)OH, C(O)OCH3, NH2, NHCH3, N(CH3)2, C(O)NH2, C(O)NHCH3 ili C(O)N(CH3)2; gdje u ostacima R3 do R15 alkil ili alkilen nije supstituiran ili je izborno jednom ili više puta supstituiran s halogenom; gdje u ostacima R3 do R15 (C6-C10) aril i (C5-C10) heteroaril nisu supstituirani ili su izborno jedan ili više puta supstituirani sa skupinom koju se neovisno bira između halogena, OH, NO2, N3, CN, C(O)-(C1-C6) alkila, C(O)-(C6-C10) arila, C(O)OH, C(O)O(C1-C6) alkila, C(O)NH2, C(O)NH(C1-C6) alkila, C(O)N[(C1-C6) alkil]2, (C3-C8) cikloalkila, (C1-C6) alkila, (C1-C6) alkilen-NH(C1-C6) alkila, (C1-C6) alkilen-N[(C1-C6) alkil]2, (C2-C6) alkenila, (C2-C6) alkinila, O-(C1-C6) alkila, O-C(O)-(C1-C6) alkila, PO3H2, SO3H, SO2-NH2, SO2NH(C1-C6) alkila, SO2N[(C1-C6) alkil]2, S-(C1-C6) alkila, SO-(C1-C6) alkila, SO2-(C1-C6) alkila, SO2-N=CH-N[(C1-C6) alkil]2, SF5, C(NH)(NH2), NH2, NH-(C1-C6) alkila, N[(C1-C6) alkil]2, NH-C(O)-(C1-C6) alkila, NH-C(O)O-(C1-C6) alkila, NH-SO2-(C1-C6) alkila, NH-SO2-(C6-C10) arila, NH-SO2-(C5-C10) heteroarila, NH-SO2-(C3-C8) heterocikloalkila, N(C1-C6) alkil-C(O)-(C1-C6) alkila, N(C1-C6) alkil-C(O)O-(C1-C6) alkila, N(C1-C6) alkil-C(O)-NH-(C1-C6) alkila, (C6-C10) aril, (C1-C6) alkilen-(C6-C10) arila, O-(C6-C10) arila, O-(C1-C6) alkilen-(C6-C10) arila, (C5-C10) heteroarila, (C3-C8) heterocikloalkila, (C1-C6) alkilen-(C5-C10) heteroarila, (C1-C6) alkilen-(C3-C8) heterocikloalkila, O-(C1-C6) alkilen-(C5-C10) heteroarila, O-(C1-C6) alkilen-(C3-C8) heterocikloalkila, gdje navedeni (C6-C10) aril ili (C5-C10) heteroaril ili (C3-C8) heterocikloalkil ili (C3-C8) cikloalkil može biti jedan do tri puta supstituiran sa skupinom koju se neovisno bira između halogena, OH, NO2, CN, O-(C1-C6) alkila, (C1-C6) alkila, NH2, NH(C1-C6) alkila, N[(C1-C6) alkil]2, SO2CH3, C(O)OH, C(O)O-(C1-C6) alkila, C(O)NH2, (C1-C6) alkilen-O-(C1-C6) alkila, (C1-C6) alkilen-O-(C6-C10) arila ili O-(C1-C6) alkilen-(C6-C10) arila; ili gdje je (C6-C10) aril vicinalno supstituiran sa skupinom O-(C1-C4) alkilen-O, gdje se 5-8-eročlani prsten formira zajedno s atomima ugljika na koje su vezani atomi kisika; i gdje arilni supstituenti (C6-C10) arilnih, (C5-C10) heteroarilnih, cikloalkilnih ili (C3-C8) heterocikloalkilnih skupina ne mogu biti daljnje supstituirani sa skupinom koja sadrži aril, heteroaril, cikloalkil ili heterocikloalkil; njihovi stereoizomerni i/ili tautomerni oblici i/ili njihove farmaceutski prihvatljive soli.
2. Spoj formule (I) u skladu s patentnim zahtjevom 1, gdje je R1 H i naznačen time što ima formulu (II) [image] .
3. Spoj formule (I) u skladu s patentnim zahtjevom 1, gdje je R1 OH i naznačen time što ima formulu (IIIa) [image] ili formulu (IIIb) [image] .
4. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je R1 NH2.
5. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time što je R3 H, halogen, (C1-C6) alkil ili NHR′, gdje (C1-C6) alkil i R′ nisu supstituirani ili su supstituirani.
6. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time što je R3 H.
7. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time što je R4 H, halogen, (C1-C6) alkil ili (C1-C2) alkenil-fenil, gdje (C1-C6) alkil ili fenil nisu supstituirani ili su supstituirani.
8. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time što je R4 H.
9. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačen time što je R5 H, halogen, (C1-C6) alkil, (C6-C10) aril, (C3-C8) cikloalkil ili (C5-C10) heteroaril, gdje (C1-C6) alkil, (C3-C8) cikloalkil, (C6-C10) aril ili (C5-C10) heteroaril nisu supstituirani ili su supstituirani.
10. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 9, naznačen time što je R5 H.
11. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačen time što je R7 H, halogen, (C1-C6) alkil, O-(C1-C6) alkil ili R′, gdje (C1-C6) alkil ili R′ nisu supstituirani ili su supstituirani.
12. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačen time što je R7 vodik, metil ili klor.
13. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 12, naznačen time što je R8 H.
14. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 13, naznačen time što je R9 R′, OH, halogen, (C1-C6) alkil, (C1-C6) alkilen-R′, (C2-C6) alkenil, (C1-C6) alkilen-C(O)NH-R′, (C1-C6) alkilen-C(O)NH-(C1-C6) alkil, COOH, CONH2, C(O)NH-(C1-C6) alkil, C(O)NHR′, C(O)-NH-(C1-C6) alkinil, C(O)-NH(C1-C6) alkilen-R′ ili C(O)N[(C1-C6) alkil]2; gdje (C1-C6) alkil, (C1-C6) alkilen ili R′are nesupstituiran ili supstituiran.
15. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 14, naznačen time što je R9 OH, halogen, (C1-C6) alkil, C(O)OH, C(O)NH2 ili O-CH3, gdje (C1-C6) alkil nije supstituiran ili je supstituiran.
16. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 15, naznačen time što je R9 nesupstituirani ili supstituirani (C1-C6) alkil.
17. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 16, naznačen time što je R10 (C1-C6) alkil, (C1-C8) heteroalkil, (C3-C8) cikloalkil, (C3-C8) heterocikloalkil, (C1-C6) alkilen-(C3-C8) cikloalkil, (C1-C6) alkilen-fenil, (C1-C6) alkilen-(C5-C6) heteroaril ili (C1-C6) alkilen-(C5-C6) heterocikloalkil, gdje (C1-C6) alkil, (C1-C8) heteroalkil, (C3-C8) cikloalkil, (C1-C6) alkilen, fenil ili (C5-C10) heteroaril nisu supstituirani ili su supstituirani.
18. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, naznačen time što je R10 metil, etil, propil, izopropil, butil, izobutil, ciklopropil, ciklobutil, ciklopentil, ciklopropilmetilen, izopropiloksimetilen, tetrahidrofuranil, tetrahidropiranil ili benzil.
19. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 18, naznačen time što je R11 H, (C1-C6) alkil, (C3-C8) cikloalkil ili (C5-C5) heteroaril, gdje (C1-C6) alkil, (C3-C8) cikloalkil ili (C5-C6) heteroaril nisu supstituirani ili su supstituirani.
20. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 19, naznačen time što je R11 H ili metil.
21. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 20, naznačen time što je R12 (C1-C6) alkil, gdje su izborno jedan ili više vodika zamijenjeni fluorom, (C3-C8) cikloalkil, (C5-C6) heteroaril ili (C6-C10) aril, gdje (C3-C8) cikloalkil, (C5-C6) heteroaril ili (C6-C10) aril nisu supstituirani ili su supstituirani.
22. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 21, naznačen time što je R12 metil, etil, propil, izopropil, ciklopropil, trifluormetil, pentafluoretil, tiazolil ili fenil.
23. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 22, naznačen time što R11 i R12 tvore supstituirani ili nesupstituirani (C3-C8) cikloalkilni prsten.
24. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 23, naznačen time što su R13 i R14 međusobno neovisno H, (C1-C6) alkil, (C3-C8) cikloalkil, (C1-C4) alkilen-(C3-C8) cikloalkil, (C1-C4) alkilen-(C5-C10) heteroaril, (C1-C4) alkilen-(C3-C8) heterocikloalkil, (C1-C4) alkilen-(C6-C10) aril, (C1-C6) alkilen-O-(C1-C6) alkil, C(O)NH-(C1-C6) alkil, ili R13 i R14, zajedno s N atomom na kojeg su vezani, tvore (C3-C8) heterocikloalkilnu skupinu, gdje (C1-C6) alkil, (C3-C8) cikloalkil, (C1-C4) alkilen, (C5-C10) heteroaril, (C3-C8) heterocikloalkil ili (C6-C10) aril nisu supstituirani ili su supstituirani.
25. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 24, naznačen time što R13 je H, (C1-C6) alkil, (C3-C8) cikloalkil ili (C1-C4) alkilen-(C3-C8) cikloalkil; i R14 je H, (C1-C6) alkil, (C3-C8) cikloalkil, (C1-C4) alkilen-(C3-C8) cikloalkil, (C1-C4) alkilen-(C5-C10) heteroaril, (C1-C4) alkilen-(C3-C8) heterocikloalkil, (C1-C4) alkilen-(C6-C10) aril, (C1-C4) alkilen-O-(C1-C6) alkil ili C(O)(C1-C6) alkil, gdje (C1-C6) alkil, (C3-C8) cikloalkil, (C1-C4) alkilen, (C5-C10) heteroaril, (C3-C8) heterocikloalkil ili (C6-C10) aril nisu supstituirani ili su supstituirani.
26. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 25, naznačen time što R13 je H ili (C1-C6) alkil; i R14 je H, (C1-C6) alkil, (C3-C8) cikloalkil, (C1-C4) alkilen-(C3-C8) cikloalkil, (C1-C4) alkilen-(C5-C10) heteroaril, (C1-C4) alkilen-(C3-C8) heterocikloalkil, (C1-C4) alkilen-(C6-C10) aril ili (C1-C4) alkilen-O-(C1-C6) alkil, gdje (C1-C6) alkil, (C3-C8) cikloalkil, (C1-C4) alkilen, (C5-C10) heteroaril, (C3-C8) heterocikloalkil ili (C6-C10) aril nisu supstituirani ili su supstituirani.
27. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 26, naznačen time što R13 je H, (C1-C6) alkil i R14 je H, (C1-C6) alkil ili (C3-C8) cikloalkil, gdje (C1-C6) alkil ili (C3-C8) cikloalkil nisu supstituirani ili su supstituirani.
28. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 27, naznačen time što su R13 i R14 H.
29. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 28, naznačen time što je R6 odsutan, ili se biciklik ili adamantan formiran s R6 bira između [image] [image] [image] [image] , koji nisu supstituirani ili su izborno supstituirani s R9.
30. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 29, naznačen time što je R6 odsutan.
31. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 30, naznačen time što je m 2, a s je 2.
32. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 30, naznačen time što je m 3, a s je 1.
33. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 32, naznačen time što je n 0, 1 ili 2.
34. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 33, naznačen time što je n 0.
35. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 34, naznačen time što je r 1.
36. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 35, naznačen time što je L S(CH2)p, S(O)(CH2)p ili SO2(CH2)p.
37. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 35, naznačen time što je L NH(CH2)p ili N((C1-C6) alkil)-(CH2)p.
38. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 35, naznačen time što je L O(CH2)p.
39. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 38, naznačen time što je p 0.
40. Spoj u skladu s patentnim zahtjevom 1, naznačen time što ga se bira iz skupine koju čine 6-[4-(1-aminopropil)-4-(tetrahidropiran-4-il)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminoetil)-4-etilciloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-propilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(aminociklopropilmetil)-4-propilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-izopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminoetil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminobutil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(aminociklopropilmetil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-amino-2-metilpropil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-izopropoksimetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminoetil)-4-ciklobutilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-ciklobutilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-ciklopentilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(aminofenilmetil)-4-ciklopentilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-metilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-izobutilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-benrilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminobutil)-4-izopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminobutil)-4-etilcikloheksiloksi]-7-metil-2H-izokinolin-1-on, 6-[4-(1-aminoetil)-4-etilcikloheksiloksi]-7-metil-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-butilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-butilcikloheksiloksi]-4-benzil-7-klor-2H-izokinolin-1-on, 6-[4-(1-amino-2,2,2-trifluoretil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-amino-2,2,2-trifluoretil)-4-izopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-amino-2,2,3,3,3-pentafluorpropil)-4-izopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(aminotiazol-2-il-metil)-4-izopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on ili 6-[4-(aminotiazol-5-il-metil)-4-izopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, njihovi stereoizomerni i/ili tautomerni oblici i/ili njihove farmaceutski prihvatljive soli.
41. Spoj u skladu s patentnim zahtjevom 1, naznačen time što ga se bira iz skupine koju čine cis-6-[4-(1-aminopropil)-4-(tetrahidropiran-4-il)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminobutil)-4-izopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminobutil)-4-etilcikloheksiloksi]-7-metil-2H-izokinolin-1-on, cis-6-[4-(1-aminoetil)-4-etilcikloheksiloksi]-7-metil-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-butilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, i cis-6-[4-(1-aminopropil)-4-butilcikloheksiloksi]-4-benzil-7-klor-2H-izokinolin-1-on, njihovi stereoizomerni i/ili tautomerni oblici i/ili njihove farmaceutski prihvatljive soli.
42. Spoj u skladu s patentnim zahtjevom 1, naznačen time što ga se bira iz skupine koju čine cis-6-[4-((S)-1-aminopropil)-4-metilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-((R)-1-aminopropil)-4-metilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-((S)-1-aminopropil)-4-(tetrahidropiran-4-il)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-((R)-1-aminopropil)-4-(tetrahidropiran-4-il)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-((R)-1-aminopropil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-((S)-1-aminopropil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-((S)-aminociklopropilmetil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, i cis-6-[4-((R)-aminociklopropilmetil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, njihovi tautomerni oblici i/ili njihove farmaceutski prihvatljive soli.
43. Spoj u skladu s patentnim zahtjevom 1, naznačen time što ga se bira iz skupine koju čine cis-6-[4-(1-aminoetil)-4-etilcikloheksiloksi]-7-metil-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-7-fluor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-7-fluor-5-metil-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-7-metil-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-5,7-dimetil-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-methoksicikloheksiloksi]-7-klor-2H-izokinolin-1-on, trans-6-[4-(1-aminopropil)-4-methoksicikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-aminopropil)-4-ethoksicikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(aminofenilmetil)-4-metilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminobutil)-4-metilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(aminofenilmetil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-amino-3-metilbutil)-4-ciklopropilmetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-amino-2-metilpropil)-4-cikloheksilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-(4,4,4-trifluorbutil)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-(tetrahidropiran-4-ilmetil)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(aminociklopropilmetil)-4-(tetrahidropiran-4-ilmetil)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(aminociklopropilmetil)-4-metilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(aminociklopropilmetil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-ethoksimetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminoetil)-4-ciklopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(aminociklopropilmetil)-4-(4,4,4-trifluorbutil)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-ciklopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(aminociklopropilmetil)-4-ciklopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-(tetrahidrothiopiran-4-il)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminoetil)-4-propilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminoetil)-4-etilcikloheksiloksi]-7-fluor-2H-izokinolin-1-on, cis-6-[4-(1-aminoetil)-4-etilcikloheksiloksi]-7-fluor-5-metil-2H-izokinolin-1-on, cis-6-[4-(1-aminoetil)-4-etilcikloheksiloksi]-4-benzil-7-klor-2H-izokinolin-1-on, cis-7-klor-6-{4-[1-(ciklopropilmetilamino)propil]-4-etilcikloheksiloksi}-2H-izokinolin-1-on, cis-6-[4-(1-benzilaminopropil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-7-klor-6-[4-etil-4-(1-izobutilaminopropil)cikloheksiloksi]-2H-izokinolin-1-on, cis-6-[4-(1-butilaminopropil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-amino-2-metilpropil)-4-izopropilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-izopropilcikloheksiloksi]-7-klor-4-fluor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-7-klor-4-fluor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-4-bromo-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-etilcikloheksiloksi]-7-klor-1-okso-1,2-dihidroizokinolin-4-karbonitril, cis-6-[4-(1-aminopropil)-4-izopropilcikloheksiloksi]-4-bromo-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-amino-2-fluoretil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, trans-6-[4-(1-amino-2-fluoretil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[4-(1-amino-3-methoksipropil)-4-etilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, cis-6-[4-(1-aminopropil)-4-(1,1-dioksotetrahidrothiopiran-4-il)cikloheksiloksi]-7-klor-2H-izokinolin-1-on, 6-[3-(1-aminopropil)-3-propilciklopentoksi]-7-klor-2H-izokinolin-1-on, i 6-[4-(1-aminopropil)-4-trifluormetilcikloheksiloksi]-7-klor-2H-izokinolin-1-on, njihovi stereoizomerni i/ili tautomerni oblici i/ili njihove farmaceutski prihvatljive soli.
44. Spoj u skladu s patentnim zahtjevom 1, naznačen time što ga se bira iz skupine koju čine cis-1-[4-(5,7-dimetilizokinolin-6-iloksi)-1-etilcikloheksil]propilamin, cis-1-[1-etil-4-(7-fluorizokinolin-6-iloksi)cikloheksil]propilamin, cis-1-[1-etil-4-(7-metilizokinolin-6-iloksi)cikloheksil]propilamin, cis-1-[1-etil-4-(7-fluor-5-metilizokinolin-6-iloksi)cikloheksil]propilamin, cis-1-[1-etil-4-(7-fluor-5-metilizokinolin-6-iloksi)cikloheksil]etilamin, cis-1-[4-(7-bromoizokinolin-6-iloksi)-1-etilcikloheksil]etilamin, cis-1-[4-(7-metilizokinolin-6-iloksi)-1-etilcikloheksil]etilamin, cis-1-[4-(5-klorizokinolin-6-iloksi)-1-etilcikloheksil]etilamin, cis-6-[4-(1-aminoetil)-4-propilcikloheksiloksi]-7-klorizokinolin-1-ilamin, i [4-(1-aminopropil)-4-metilcikloheksil]izokinolin-6-il-amin, i njihovi stereoizomerni i/ili tautomerni oblici i/ili njihove farmaceutski prihvatljive soli.
45. Spoj formule (I) i/ili njegova farmaceutski prihvatljiva sol u skladu s bilo kojim od patentnih zahtjeva 1 do 44, naznačen time što je namijenjen upotrebi kao medikament.
46. Upotreba najmanje jednog spoja formule (I) i/ili njegove farmaceutski prihvatljive soli u skladu s bilo kojim od patentnih zahtjeva 1 do 44, naznačena time što je spoj namijenjen proizvodnji medikamenta.
47. Upotreba najmanje jednog spoja formule (I) i/ili njegove farmaceutski prihvatljive soli u skladu s bilo kojim od patentnih zahtjeva 1 do 44, naznačena time što je spoj namijenjen proizvodnji farmaceutskih pripravaka za liječenje i/ili sprječavanje hipertenzije, plućne hipertenzije, očne hipertenzije, retinopatije, glaukoma, poremećaja perifernog krvotoka, okluzivne bolesti perifernih arterija (PAOD), kornarne bolesti srca, angine pektoris, hipertrofije srca, srčane insuficijencije, ishemične bolesti, ishemične organske insuficijencije (krajnjeg oštećenja organa), fibroze pluća, fibroze jetre, jetrene insuficijencije, nefropatije, bubrežne insuficijencija, fibroze bubrega, glomeruloskleroze bubrega, hipertrofija organa, astme, kronične opstruktivne plućne bolesti (COPD), sindroma respiratornog distresa kod odraslih, trombotskih poremećaja, inzulta, cerebralnog vazospazma, cerebralne ishemije, boli, degeneracije neurona, ozljede kralježnične moždine, Alzheimerove bolesti, prijevremenog poroda, erektilne disfunkcije, endokrinih disfunkcija, arterioskleroze, hipertrofije prostate, dijabetesa i komplikacija dijabetesa, metaboličkog sindroma, restenoze krvnih žila, ateroskleroze, upale, autoimunih bolesti, AIDS-a, osteopatije, bakterijske infekcije probavnog sustava, sepse ili razvoja i napredovanja raka.
48. Upotreba spoja formule (I) i/ili njegove farmaceutski prihvatljive soli u skladu s bilo kojim od patentnih zahtjeva 1 do 44, naznačena time što je spoj namijenjen proizvodnji farmaceutskih pripravaka za liječenje i/ili sprječavanje hipertenzije, plućne hipertenzije, fibroze jetre, jetrene insuficijencija, nefropatije, bubrežne insuficijencije, kronične opstruktivne plućne bolesti (COPD), cerebralnog vazospazam, boli, ozljede kralježnične moždine, erektilne disfunkcije, restenoze krvnih žila, ili razvoja i napredovanja raka.
49. Spoj formule (I) i/ili njegova farmaceutski prihvatljiva sol u skladu s bilo kojim od patentnih zahtjeva 1 do 44, naznačen time što je namijenjen upotrebi u postupcima liječenja povezanim s liječenjem matičnim stanicama ili induciranim pluripotentnim matičnim stanicama, poboljšavanjem prepoznavanja ili namijenjenim liječenju ili sprječavanju fibroze srca, depresije, epilepsije, nekroze bubrežnih papila, disfunkcija intersticija tubula, multiple skleroze, stenoze krvnih žila ili poremećaja lipida.
50. Medikament, naznačen time što sadrži djelotvornu količinu najmanje jednog spoja formule (I) i/ili njegove farmakološki prihvatljive soli u skladu s bilo kojim od patentnih zahtjeva 1 do 44, farmaceutski podnošljive pomoćne tvari i podloge i, gdje je to prikladno, dodatne aditive i/ili druge aktivne sastojke.
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