HRP20161797T1 - Spojevi 1,3-oksazolidina ili 1,3-oksazinana kao antagonisti receptora oreksina - Google Patents

Spojevi 1,3-oksazolidina ili 1,3-oksazinana kao antagonisti receptora oreksina Download PDF

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HRP20161797T1
HRP20161797T1 HRP20161797TT HRP20161797T HRP20161797T1 HR P20161797 T1 HRP20161797 T1 HR P20161797T1 HR P20161797T T HRP20161797T T HR P20161797TT HR P20161797 T HRP20161797 T HR P20161797T HR P20161797 T1 HRP20161797 T1 HR P20161797T1
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methyl
methanone
pyrazol
phenyl
triazol
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HRP20161797TT
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Aya FUTAMURA
Yuko Araki
Masahito Abe
Hiroshi Ohta
Ryo Suzuki
Dai Nozawa
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Taisho Pharmaceutical Co., Ltd
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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Claims (9)

1. Spoj predstavljen s formulom (IA): [image] naznačen time da, X1 i X2 su isti ili različiti i predstavljaju dušikov atom ili formulu CH; Y predstavlja bilo koju od struktura iz slijedeće skupine formula (a): [image] n predstavlja 1 ili 2; R1 predstavlja vodikov atom, halogeni atom ili skupinu C1-6 alkil; R2 predstavlja triazolil skupinu, piridil skupinu ili pirimidinil skupinu; R3 predstavlja vodikov atom, halogeni atom ili skupinu C1-6 alkil, pri čemu skupina C1-6 alkil može proizvoljno biti supstituirana s 1 do 3 halogenih atoma; i R4 predstavlja vodikov atom ili skupinu C1-6 alkil; ili njegova farmaceutski prihvatljiva sol.
2. Spoj ili njegova farmaceutski prihvatljiva sol prema zahtjevu 1, naznačen time da, u gornjoj formuli (IA), R2 je skupina triazolil ili skupina pirimidinil; i R3 je halogeni atom.
3. Spoj ili njegova farmaceutski prihvatljiva sol prema zahtjevu 1 ili 2, naznačen time da, u gornjoj formuli (IA), n je 2.
4. Spoj ili njegova farmaceutski prihvatljiva sol prema zahtjevu 1 prikazan s formulom (I): [image] naznačen time da, X1 i X2 su isti ili različiti i predstavljaju dušikov atom ili formulu CH; bilo koji od Y1 i Y2 predstavlja dušikov atom, dok drugi predstavlja CH; n predstavlja 1 ili 2; R1 predstavlja vodikov atom, halogeni atom ili skupinu C1-6 alkil; R2 predstavlja triazolil skupinu, piridil skupinu ili pirimidinil skupinu; R3 predstavlja vodikov atom, halogeni atom ili skupinu C1-6 alkil, pri čemu skupina C1-6 alkil može proizvoljno biti supstituirana s 1 do 3 halogena atoma; te R4 predstavlja vodikov atom ili skupinu C1-6 alkil; ili njegova farmaceutski prihvatljiva sol.
5. Spoj ili njegova farmaceutski prihvatljiva sol prema zahtjevu 4, naznačen time da, u gornjoj formuli (I), R2 je skupina triazolil ili skupina pirimidinil; i R3 je halogeni atom.
6. Spoj ili njegova farmaceutski prihvatljiva sol prema zahtjevu 4 ili 5, naznačen time da, u gornjoj formuli (I), n je 2.
7. Spoj ili njegova farmaceutski prihvatljiva sol prema zahtjevu 1, naznačen time da je vrsta ili mješavina dviju ili više vrsta koje su odabrane iz skupa koji sadrži: (-)-(2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazolidin-3-il)[5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-(2-{[4-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazolidin-3-il)[5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-(2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il)[5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-(2-{[4-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il)[5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-[(2S,5S)-2-{[4-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-5-metil-1,3-oksazolidin-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-[(2S,5R)-2-{[4-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-5-metil-1,3-oksazolidin-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, [(2S,4R)-2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-4-metil-1,3-oksazolidin-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-[(2S,4S)-2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-4-metil-1,3-oksazolidin-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (±)-2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazolidin-3-il] [5-metil-2-(pirimidin-2-il)fenil]metanon, (±)-(2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazolidin-3-il)[5-fluor-2-(pirimidin-2-il)fenil]metanon, (±)-(2-{[3-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazolidin-3-il)[5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (±)-(2-{[4-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazolidin-3-il)[5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (±)-(2-{[4-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazolidin-3-il)[5-metil-2-(pirimidin-2-il)fenil]metanon, (-)-(2-{{[3-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazolidin-3-il)[6-metil-3-(2H-1,2,3-triazol-2-il)piridin-2-il]metanon, (-)-(2-{[3-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il)[6-metil-3-(2H-1,2,3-triazol-2-il)piridin-2-il]metanon, (-)-(2-{[3-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il)[6-metil-3-(pirimidin-2-il)piridin-2-il]metanon, (-)-(2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il)[5-fluor-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-(2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il)[5-metil-2-(pirimidin-2-il)fenil]metanon, (-)-(2-{[4-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il)[6-metil-3-(2H-1,2,3-triazol-2-il)piridin-2-il]metanon, (-)-(2-{[4-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il)[6-metil-3-(pirimidin-2-il)piridin-2-il]metanon, (-)-[2-{[3-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il] [5-fluor-2-(pirimidin-2-il)fenil]metanon, (-)-[2-{[4-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-[2-{[5-(5-fluorpiridin-2-il)-1,2,4-oksadiazol-3-il]metil}-1,3-oksazinan-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-[2-{[5-(4-fluorfenil)-1,2,4-oksadiazol-3-il]metil}-1,3-oksazinan-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil] metanon, (-)-[2-{[5-(4-fluorfenil)-1,2,4-oksadiazol-3-il]metil}-1,3-oksazinan-3-il] [6-metil-3-(2H-1,2,3-triazol-2-il)piridin-2-il]metanon, [(2S,4S)-2-{[4-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-4-metil-1,3-oksazinan-3-il[5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-[(2S*,5S*)-2-{[4-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-5-metil-1,3-oksazinan-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon, (-)-[2-{[3-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il] [5-metil-2-(pirimidin-2-il)fenil]metanon, (±)-[2-{[1-(5-fluorpiridin-2-il)-1H-pirazol-4-il]metil}-1,3-oksazinan-3-il] [5-metil-2-(pirimidin-2-il)fenil]metanon, (-)- [2-{[4-(4-fluorfenil)-1H-pirazol-1-il]metil}-1,3-oksazinan-3-il] [5-metil-2-(pirimidin-2-il)fenil]metanon, (-)-[2-{[1-(5-fluorpiridin-2-il)-1H-pirazol-4-il]metil}-1,3-oksazinan-3-il] [5-fluor-2-(pirimidin-2-il)fenil]metanon, (-)-[2-[1-(5-fluorpiridin-2-il)-1H-pirazol-3-il]metil}-1,3-oksazolidin-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil] metanon, (-)-[2-{[1-(5-fluorpiridin-2-il)-1H-pirazol-4-il]metil}-1,3-oksazolidin-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil] metanon, (-)-[2-{[1-(5-fluorpiridin-2-il)-1H-pirazol-4-il]metil}-1,3-oksazinan-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil] metanon, (-)-[(2S*,5R*)-2-{[4-(5-fluorpiridin-2-il)-1H-pirazol-1-il]metil}-5-metil-1,3-oksazinan-3-il] [5-metil-2-(2H-1,2,3-triazol-2-il)fenil]metanon.
8. Farmaceutski pripravak naznačen time da kao aktivni sastojak sadrži spoj ili njegovu farmaceutski prihvatljivu sol prema bilo kojem od zahtjeva 1 do 7.
9. Lijek koji kao aktivni sastojak sadrži spoj ili njegovu farmaceutski prihvatljivu sol prema bilo kojem od zahtjeva 1 do 7, naznačen time da je za upotrebu za liječenje ili prevenciju bolesti, kao što su poremećaj spavanja, depresija, anksioznost, poremećaj panike, shizofrenija, ovisnost o lijekovima, Alzheimerova bolest, Parkinsonova bolest, Huntingtonova bolest, poremećaj hranjenja, glavobolja, migrena, bol, gastrointestinalna bolest, epilepsija, upala, imunološka bolest, endokrina bolest ili hipertenzija.
HRP20161797TT 2012-06-15 2016-12-27 Spojevi 1,3-oksazolidina ili 1,3-oksazinana kao antagonisti receptora oreksina HRP20161797T1 (hr)

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JP2012135277 2012-06-15
PCT/JP2013/066322 WO2013187467A1 (ja) 2012-06-15 2013-06-13 ヘテロ芳香環メチル環状アミン誘導体
EP13804876.4A EP2862860B1 (en) 2012-06-15 2013-06-13 1,3-oxazolidine or 1,3-oxazinane compounds as orexin receptor antagonists

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