HRP20211778T1 - Kontrastna sredstva za slikovnu dijagnostiku huntingtin proteina - Google Patents

Kontrastna sredstva za slikovnu dijagnostiku huntingtin proteina Download PDF

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HRP20211778T1
HRP20211778T1 HRP20211778TT HRP20211778T HRP20211778T1 HR P20211778 T1 HRP20211778 T1 HR P20211778T1 HR P20211778T T HRP20211778T T HR P20211778TT HR P20211778 T HRP20211778 T HR P20211778T HR P20211778 T1 HRP20211778 T1 HR P20211778T1
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methoxy
methoxypyridin
pyridin
benzoxazole
benzoxazol
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HRP20211778TT
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Celia Dominguez
John Wityak
Jonathan Bard
Alex Kiselyov
Christopher John Brown
Sebastien Rene Gabriel Galan
Michael Edward PRIME
Paul Richard Giles
Elise Lucienne Paulette Gadouleau
Thomas Martin KRÜLLE
Daniel CLARK-FREW
Peter David Johnson
Samuel COE
Sarah HAYES
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Chdi Foundation, Inc.
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Claims (18)

1. Sredstvo za slikovnu dijagnostiku, naznačeno time, da sadrži spoj Formule (I): [image] ili njegovu farmaceutski prihvatljivu sol, u kojoj X se odabire od NR4, O i S; Y se odabire od CR4 i N; Z1, Z2, Z3 i Z4 se neovisno odabiru od CH i N, uz uvjet da najmanje dva od Z1, Z2, Z3 i Z4 jesu CH; R1 se odabire od heteroarila, heterocikloalkenila i heterocikloalkila, od kojih je svaki opcionalno supstituiran s jednom ili dvije skupine neovisno odabrane od cijano, halogena, C1-6 alkila opcionalno supstituiranog s amino, alkilamino, ili di(alkil)amino, C1-6 alkoksi opcionalno supstituiranog s C1-6 alkoksi, opcionalno supstituiranog amino, haloalkila, di(alkil)aminokarbonila, alkilaminokarbonila i aminokarbonila; ili R1 je fenil opcionalno supstituiran s jednom ili dvije skupine koje se neovisno odabiru od cijano, heteroarila, halogena, fenoksi, benziloksi, heteroarila, C1-6 alkila opcionalno supstituiranog s amino, (alkil)amino, ili di(alkil)amino, C1-6 alkoksi, opcionalno supstituiranog amino, di(alkil)aminokarbonila, alkilaminokarbonila i aminokarbonila; L1 je -O- i L2 je –(CR7R8)m-; L3 je -CH=CH-, ili je L3 odsutan; R2 je piridin-2-il ili piridin-3-il, od kojih je svaki opcionalno supstituiran s jednom ili dvije skupine koje se neovisno odabiru od C1-6 alkila, hidroksila, C1-6 alkoksi, C1-6 alkoksi supstituiranog s amino, (alkil)amino, (dialkil)amino, ili C1-6 alkoksi, i C1-6 alkila supstituiranog s hidroksilom, C1-6 alkoksi, amino, (alkil)amino, ili (dialkil)amino; R4 se odabire od vodika, halogena, cijano i C1-6 alkila; R5 se odabire od C1-6 alkila, C1-6 alkoksi i halogena; R7 se odabire od vodika, hidroksila, trifluorometila i C1-6 alkila; R8 se odabire od vodika i C1-6 alkila; n je 0 ili 1; i m je 0, 1 ili 2; pri čemu se spoj Formule I ili njegova farmaceutski prihvatljiva sol označava s jednim ili više radionuklida koji emitiraju pozitrone.
2. Sredstvo za slikovnu dijagnostiku prema patentnom zahtjevu 1, naznačeno time, da se R1 odabire od sljedećih: fenil, piridin-2-il, piridin-3-il, piridin-3-il-1-oksid, piridin-4-il, 1H-pirazol-4-il, pirazin-2-il, piridazin-3-il, piridazin-4-il, pirimidin-4-il, pirimidin-5-il, 2,3-dihidro-piridazin-3-on-6-il, 1,2-dihidropiridin-2-on-5-il, 1,2-dihidropirazin-2-on-5-il, 1,3-tiazol-5-il, 5,6,7,8-tetrahidro-1,7-naftiridin-7-il, 1H-imidazol-1-il, 1-benzofuran-2-il, 1-benzofuran-5-il, 2,3-dihidro-1-benzofuran-2-il, kinolon-2-il, i 5H,6H,7H,8H-imidazo[1,2-a]pirazin-7-il, od kojih je svaki opcionalno supstituiran s jednom ili dvije skupine neovisno odabrane od halogena, C1-6 alkila, C1-6 alkoksi i opcionalno supstituiranog amino.
3. Sredstvo za slikovnu dijagnostiku prema patentnom zahtjevu 1, naznačeno time, da R1 jest: [image] gdje W se odabire od CH, N i N(O); p se odabire od 0, 1 i 2; u svakom pojavljivanju R9 se neovisno odabire od cijano, halogena, C1-6 alkila, C1-6 haloalkila, C1-6 alkila supstituiranog s -NR10R11, C1-6 alkoksi, -C(O)NR10R11 i -NR10R11; R10 se odabire od vodika i C1-6 alkila; R11 se odabire od vodika, C1-6 alkila i -C(O)R12; i R12 se odabire od vodika i C1-6 alkila; opcionalno, pritom W je CH, ili, pritom W je N, ili, pritom W je N(O).
4. Sredstvo za slikovnu dijagnostiku prema patentnom zahtjevu 3, naznačeno time, da W je CH ili N, pri čemu p je 1 ili pri čemu p je 0.
5. Sredstvo za slikovnu dijagnostiku prema patentnom zahtjevu 3, naznačeno time, da W je N(O) i time, da se R9 odabire od cijano, halogena, metila i metoksi.
6. Sredstvo za slikovnu dijagnostiku prema patentnom zahtjevu 1, naznačeno time, da R1 jest: [image] gdje W1 i W2 se odabiru od CH i N, uz uvjet da najmanje jedan od W1 i W2 bude CH; p se odabire od 0, 1 i 2; i u svakom pojavljivanju R9 se neovisno odabire od C1-6 alkila.
7. Sredstvo za slikovnu dijagnostiku prema patentnom zahtjevu 2, naznačeno time, da R1 je 1H-pirazol-4-il opcionalno supstituiran s C1-6 alkilom.
8. Sredstvo za slikovnu dijagnostiku prema bilo kojem od patentnih zahtjeva 1 do 7, naznačeno time, da X je O; ili, time, da X je S; ili, time, da X je NR4.
9. Sredstvo za slikovnu dijagnostiku prema bilo kojem od patentnih zahtjeva 1 do 8, naznačeno time, da Y je CR4 ili time, da Y je N; opcionalno, pritom R4 je vodik; ili, pritom R4 je halogen, primjerice, gdje R4 je bromo; ili, pritom R4 je cijano; ili, pritom R4 je C1-6 alkil, primjerice, gdje R4 je metil.
10. Sredstvo za slikovnu dijagnostiku prema bilo kojem od patentnih zahtjeva 1 do 9, naznačeno time, da Z1, Z2, Z3 i Z4 su CH; ili, time, da Z1 je N i Z2, Z3 i Z4 su CH; ili, time, da Z2 je N i Z1, Z3 i Z4 su CH; ili, time, da Z2 i Z4 su N i Z1 i Z3 su CH.
11. Sredstvo za slikovnu dijagnostiku prema patentnom zahtjevu 1, naznačeno time, da se spoj odabire od sljedećih: 4-{5-[(5-metoksipiridin-2-il)metoksi]-1-benzofuran-2-il}piridin-3-karbonitril; 4-{5-[(5-metoksipiridin-2-il)metoksi]-1-benzofuran-2-il}piridin; 4-[5-(piridin-3-iloksi)-1-benzofuran-2-il]piridin-3-karbonitril; 5-[(5-metoksipiridin-2-il)metoksi]-2-(piridin-3-il)-1,3-benzoksazol; 2-(piridin-3-il)-5-(piridin-3-ilmetoksi)-1,3-benzoksazol; 2-(piridin-3-il)-6-(piridin-3-ilmetoksi)-1,3-benzoksazol; 4-[5-(piridin-3-ilmetoksi)-1-benzofuran-2-il]piridin-3-karbonitril; 3-[5-(piridin-3-ilmetoksi)-1-benzofuran-2-il]piridin-4-karbonitril; 3-{6-[1-(5-metoksipiridin-2-il)etoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}piridin; 6-({[2-(piridin-3-il)-1,3-benzoksazol-5-il]oksi}metil)piridin-3-ol; 3-{6-[(5-metoksipiridin-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}piridin; 3-{6-[(6-metoksipiridin-3-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}piridin; 5-[(5-metoksipiridin-2-il)metoksi]-2-(piridin-4-il)-1,3-benzoksazol; [(3-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}fenil)metil]dimetilamin; 5-[(5-metoksipiridin-2-il)metoksi]-2-(1-metil-1H-pirazol-4-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(pirazin-2-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(1-metilpiperidin-4-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(1,3-tiazol-5-il)-1,3-benzoksazol; 3-{[(2-{5H,6H-imidazo[2,1-b][1,3]tiazol-3-il}-1-benzofuran-5-il}oksi]metil}piridin; 2-(3-fluoroazetidin-1-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-{3H,4H,5H,6H,7H-imidazo-[4,5-c]piridin-5-il}-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-{2H,4H,5H,6H,7H-pirazolo-[4,3-c]piridin-5-il}-1,3-benzoksazol; 2-{5H,6H,7H,8H-imidazo-[1,5-a]pirazin-7-il}-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-{5H,6H,7H-pirolo-[3,4-b]piridin-6-il}-1,3-benzoksazol; 7-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-5,6,7,8-tetrahidro-1,7-naftiridin; 2-(1H-imidazol-1-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-{5H,6H,7H,8H-imidazo-[1,2-a]pirazin-7-il}-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-[5-(2-metoksietoksi)piridin-3-il]-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; N-(5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-piridin-2-il)acetamid; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-piridin-2-amin; 5-{[5-(2-metoksietoksi)piridin-2-il]metoksi}-2-(piridin-3-il)-1,3-benzoksazol; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-N-metilpiridin-2-amin; 3-{[(2-{2-bromo-5H,6H-imidazo[2,1-b][1,3]tiazol-3-il}-1-benzofuran-5-il)oksi]metil}piridin; 5-[(5-metokspiridin-2-il)metoksi]-2-(piperazin-1-il)-1,3-benzoksazol; 3-[5-(piridin-3-ilmetoksi)-1-benzofuran-2-il]-5H,6H-imidazo[2,1-b][1,3]tiazol-2-karbonitril; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-N-metilpiridin-2-karboksamid; 5-[(5-metokspiridin-2-il)metoksi]-2-(1-metil-1H-imidazol-4-il)-1,3-benzoksazol; 5-({5-[2-(morfolin-4-il)etoksi]piridin-2-il}metoksi)-2-(piridin-3-il)-1,3-benzoksazol; 2-bromo-6-{5-[(5-metokspiridin-2-il)metoksi]-1-benzofuran-2-il}benzonitril; 3-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-piridin-1-ij-1-olat; 5-[(5-metokspiridin-2-il)metoksi]-2-(pirimidin-5-il)-1,3-benzoksazol; 2-(2,3-dihidro-1-benzofuran-2-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-[(2R)-2,3-dihidro-1-benzofuran-2-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-[(2S)-2,3-dihidro-1-benzofuran-2-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(5-metilpiridin-3-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(2-metilpiridin-4-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(3-fenoksifenil)-1,3-benzoksazol; 6-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-2-metil-2,3-dihidropiridazin-3-on; 5-[(5-metoksipiridin-2-il)metoksi]-2-(piridazin-3-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(piridazin-4-il)-1,3-benzoksazol; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-1,2-dihidropiridin-2-on; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-1-metil-1,2-dihidropiridin-2-on; 5-[(5-metoksipiridin-2-il)metoksi]-2-(pirimidin-4-il)-1,3-benzoksazol; 5-(piridin-2-ilmetoksi)-2-(piridin-3-il)-1,3-benzoksazol; 6-({[2-(1-metil-1H-pirazol-4-il)-1,3-benzoksazol-5-il]oksi}metil)piridin-3-ol; 3-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}benzonitril; 4-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}benzonitril; 3-metoksi-5-({[2-(piridin-3-il)-[1,3]oksazolo[5,4-b]piridin-6-il]oksi}metil)piridin; 4-metoksi-2-({[2-(piridin-3-il)-[1,3]oksazolo[5,4-b]piridin-6-il]oksi}metil)piridin; [(3-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}fenil)metil](metil)amin; 2-(5-metoksipiridin-2-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-(1-benzofuran-2-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-[6-(trifluorometil)piridin-3-il]-1,3-benzoksazol; 2-(1-benzofuran-5-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}kinolin; 2-[3-(benziloksi)fenil]-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-[4-(pirimidin-2-il)fenil]-1,3-benzoksazol; 2-[(E)-2-(4-metoksifenil)etenil]-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-{5-[(5-hidroksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-N-metilpiridin-2-karboksamid; 6-{6-[(5-metoksipiridin-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}-2-metil-2,3-dihidropiridazin-3-on; 2-{6-[(5-metoksipiridin-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}pirazin; 5-{6-[(5-metoksipiridin-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}-N-metilpiridin-2-karboksamid; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-1-metil-1,2-dihidropirazin-2-on; 5-metoksi-2-({[2-(piridin-3-il)-[1,3]oksazolo[5,4-b]piridin-6-il]oksi}metil)piridin-1-ij-1-olat; 3-{6-[(5-metoksi-1-oksidopiridin-1-ij-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}piridin-1-ij-1-olat; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-2-(metilkarbamoil)piridin-1-ij-olat; [(5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}piridin-3-il)metil](metil)amin; i 6-{5-[(5-hidroksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-2-metil-2,3-dihidropiridazin-3-on.
12. Sredstvo za slikovnu dijagnostiku prema bilo kojem od patentnih zahtjeva 1 do 11, naznačeno time, da se navedeni jedan ili više radionuklida koji emitiraju pozitrone, biraju od: 11C, 13N, 15O i 18F.
13. Postupak generiranja dijagnostičkih slika kod pojedinca, naznačen time, da obuhvaća davanje pojedincu učinkovite količine sredstva za slikovnu dijagnostiku prema bilo kojem od patentnih zahtjeva 1 do 12, i generiranje slikovnog prikaza od najmanje jednog dijela navedenog pojedinca.
14. Sredstvo za slikovnu dijagnostiku prema bilo kojem od patentnih zahtjeva 1 do 12, naznačeno time, da je za uporabu u postupku generiranja dijagnostičkih slika kod pojedinca, koji obuhvaća davanje pojedincu učinkovite količine sredstva za slikovnu dijagnostiku prema bilo kojem od patentnih zahtjeva 1 do 12, i generiranje slikovnog prikaza od najmanje jednog dijela navedenog pojedinca, pri čemu generiranje slikovnog prikaza od najmanje jednog dijela navedenog pojedinca, obuhvaća generiranje slikovnog prikaza za detekciju prisutnosti ili odsutnosti agregata huntingtin proteina (HTT proteina) u mozgu navedenog pojedinca; i detektiranje prisutnosti ili odsutnosti patološkog procesa; opcionalno, pri čemu se spomenuti agregati HTT proteina nalaze u bazalnim ganglijima spomenutog mozga navedenog pojedinca.
15. Sredstvo za slikovnu dijagnostiku za uporabu prema patentnom zahtjevu 14, naznačeno time, da patološki proces jest neurodegenerativna bolest, primjerice, pri čemu se neurodegenerativna bolest odabire od Alzheimerove bolesti, amiotrofične lateralne skleroze, Huntingtonove bolesti, Parkinsonove bolesti, prionske bolesti i spinocerebelarne ataksije, primjerice, pri čemu neurodegenerativna bolest jest Huntingtonova bolest (HD).
16. Postupak prema patentnom zahtjevu 13 ili sredstvo za slikovnu dijagnostiku za uporabu prema bilo kojem od patentnih zahtjeva 14 do 15, naznačeni time, da spomenuta učinkovita količina navedenog sredstva za slikovnu dijagnostiku sadrži od oko 0,1 do oko 20 mCi, primjerice, gdje spomenuta učinkovita količina navedenog sredstva za slikovnu dijagnostiku sadrži oko 10 mCi.
17. Postupak prema patentnom zahtjevu 13 ili 16, ili sredstvo za slikovnu dijagnostiku za uporabu prema bilo kojem od patentnih zahtjeva 14 do 16, naznačeni time, da spomenuto generiranje slikovnog prikaza obuhvaća prikazivanje pozitronske emisijske tomografije (PET), PET s istovremenim prikazivanjem računalne tomografije (PET/CT), PET s istovremenim prikazivanjem magnetske rezonancije (PET/MRI), ili njihovu kombinaciju, primjerice, gdje spomenuto generiranje slikovnog prikaza obuhvaća PET slikovno prikazivanje.
18. Spoj, naznačen time, da je predstavljen formulom: 4-{5-[(5-metoksipiridin-2-il)metoksi]-1-benzofuran-2-il}piridin-3-karbonitril; 4-{5-[(5-metoksipiridin-2-il)metoksi]-1-benzofuran-2-il}piridin; 4-[5-(piridin-3-iloksi)-1-benzofuran-2-il]piridin-3-karbonitril; 5-[(5-metoksipiridin-2-il)metoksi]-2-(piridin-3-il)-1,3-benzoksazol; 2-(piridin-3-il)-5-(piridin-3-ilmetoksi)-1,3-benzoksazol; 2-(piridin-3-il)-6-(piridin-3-ilmetoksi)-1,3-benzoksazol; 4-[5-(piridin-3-ilmetoksi)-1-benzofuran-2-il]piridin-3-karbonitril; 3-[5-(piridin-3-ilmetoksi)-1-benzofuran-2-il]piridin-4-karbonitril; 3-{6-[1-(5-metoksipiridin-2-il)etoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}piridin; 6-({[2-(piridin-3-il)-1,3-benzoksazol-5-il]oksi}metil)piridin-3-ol; 3-{6-[(5-metoksipiridin-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}piridin; 3-{6-[(6-metoksipiridin-3-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}piridin; 5-[(5-metoksipiridin-2-il)metoksi]-2-(piridin-4-il)-1,3-benzoksazol; [(3-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}fenil)metil]dimetilamin; 5-[(5-metoksipiridin-2-il)metoksi]-2-(1-metil-1H-pirazol-4-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(pirazin-2-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(1-metilpiperidin-4-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(1,3-tiazol-5-il)-1,3-benzoksazol; 3-{[(2-{5H,6H-imidazo[2,1-b][1,3]tiazol-3-il}-1-benzofuran-5-il}oksi]metil}piridin; 2-(3-fluoroazetidin-1-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-{3H,4H,5H,6H,7H-imidazo-[4,5-c]piridin-5-il}-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-{2H,4H,5H,6H,7H-pirazolo-[4,3-c]piridin-5-il}-1,3-benzoksazol; 2-{5H,6H,7H,8H-imidazo-[1,5-a]pirazin-7-il}-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-{5H,6H,7H-pirolo-[3,4-b]piridin-6-il}-1,3-benzoksazol; 7-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-5,6,7,8-tetrahidro-1,7-naftiridin; 2-(1H-imidazol-1-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-{5H,6H,7H,8H-imidazo-[1,2-a]pirazin-7-il}-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-[5-(2-metoksietoksi)piridin-3-il]-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; N-(5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-piridin-2-il)acetamid; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-piridin-2-amin; 5-{[5-(2-metoksietoksi)piridin-2-il]metoksi}-2-(piridin-3-il)-1,3-benzoksazol; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-N-metilpiridin-2-amin; 3-{[(2-{2-bromo-5H,6H-imidazo[2,1-b][1,3]tiazol-3-il}-1-benzofuran-5-il)oksi]metil}-piridin; 5-[(5-metokspiridin-2-il)metoksi]-2-(piperazin-1-il)-1,3-benzoksazol; 3-[5-(piridin-3-ilmetoksi)-1-benzofuran-2-il]-5H,6H-imidazo[2,1-b][1,3]tiazol-2-karbonitril; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-N-metilpiridin-2-karboksamid; 5-[(5-metokspiridin-2-il)metoksi]-2-(1-metil-1H-imidazol-4-il)-1,3-benzoksazol; 5-({5-[2-(morfolin-4-il)etoksi]piridin-2-il}metoksi)-2-(piridin-3-il)-1,3-benzoksazol; 2-bromo-6-{5-[(5-metokspiridin-2-il)metoksi]-1-benzofuran-2-il}benzonitril; 3-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}piridin-1-ij-1-olat; 5-[(5-metokspiridin-2-il)metoksi]-2-(pirimidin-5-il)-1,3-benzoksazol; 2-(2,3-dihidro-1-benzofuran-2-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-[(2R)-2,3-dihidro-1-benzofuran-2-il]-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-[(2S)-2,3-dihidro-1-benzofuran-2-il]-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(5-metilpiridin-3-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(2-metilpiridin-4-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(3-fenoksifenil)-1,3-benzoksazol; 6-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-2-metil-2,3-dihidropiridazin-3-on; 5-[(5-metoksipiridin-2-il)metoksi]-2-(piridazin-3-il)-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-(piridazin-4-il)-1,3-benzoksazol; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-1,2-dihidropiridin-2-on; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-1-metil-1,2-dihidropiridin-2-on; 5-[(5-metoksipiridin-2-il)metoksi]-2-(pirimidin-4-il)-1,3-benzoksazol; 5-(piridin-2-ilmetoksi)-2-(piridin-3-il)-1,3-benzoksazol; 6-({[2-(1-metil-1H-pirazol-4-il)-1,3-benzoksazol-5-il]oksi}metil)piridin-3-ol; 3-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}benzonitril; 4-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}benzonitril; 3-metoksi-5-({[2-(piridin-3-il)-[1,3]oksazolo[5,4-b]piridin-6-il]oksi}metil)piridin; 4-metoksi-2-({[2-(piridin-3-il)-[1,3]oksazolo[5,4-b]piridin-6-il]oksi}metil)piridin; [(3-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}fenil)metil](metil)amin; 2-(5-metoksipiridin-2-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-(1-benzofuran-2-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-[6-(trifluorometil)piridin-3-il]-1,3-benzoksazol; 2-(1-benzofuran-5-il)-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 2-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}kinolin; 2-[3-(benziloksi)fenil]-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-[(5-metoksipiridin-2-il)metoksi]-2-[4-(pirimidin-2-il)fenil]-1,3-benzoksazol; 2-[(E)-2-(4-metoksifenil)etenil]-5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol; 5-{5-[(5-hidroksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-N-metilpiridin-2-karboksamid; 6-{6-[(5-metoksipiridin-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}-2-metil-2,3-dihidropiridazin-3-on; 2-{6-[(5-metoksipiridin-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}pirazin; 5-{6-[(5-metoksipiridin-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}-N-metilpiridin-2-karboksamid; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-1-metil-1,2-dihidropirazin-2-on; 5-metoksi-2-({[2-(piridin-3-il)-[1,3]oksazolo[5,4-b]piridin-6-il]oksi}metil)piridin-1-ij-1-olat; 3-{6-[(5-metoksi-1-oksidopiridin-1-ij-2-il)metoksi]-[1,3]oksazolo[5,4-b]piridin-2-il}piridin-1-ij-1-olat; 5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-2-(metilkarbamoil)piridin-1-ij-olat; [(5-{5-[(5-metoksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}piridin-3-il)metil](metil)amin; ili 6-{5-[(5-hidroksipiridin-2-il)metoksi]-1,3-benzoksazol-2-il}-2-metil-2,3-dihidropiridazin-3-on.
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