DK2862860T3 - 1,3-oxazolidin- eller 1,3-oxazinanforbindelser som orexinreceptorantagonister - Google Patents
1,3-oxazolidin- eller 1,3-oxazinanforbindelser som orexinreceptorantagonister Download PDFInfo
- Publication number
- DK2862860T3 DK2862860T3 DK13804876.4T DK13804876T DK2862860T3 DK 2862860 T3 DK2862860 T3 DK 2862860T3 DK 13804876 T DK13804876 T DK 13804876T DK 2862860 T3 DK2862860 T3 DK 2862860T3
- Authority
- DK
- Denmark
- Prior art keywords
- methyl
- methanone
- pyrazol
- phenyl
- triazol
- Prior art date
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- 229940123730 Orexin receptor antagonist Drugs 0.000 title description 2
- LQPOOAJESJYDLS-UHFFFAOYSA-N 1,3-oxazinane Chemical class C1CNCOC1 LQPOOAJESJYDLS-UHFFFAOYSA-N 0.000 title 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 220
- 239000000203 mixture Substances 0.000 claims description 73
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- -1 5-fluoropyridin-2-yl Chemical group 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000001425 triazolyl group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
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- AEZZJXJIJFSUEM-UHFFFAOYSA-N [2-[[3-(5-fluoropyridin-2-yl)pyrazol-1-yl]methyl]-1,3-oxazinan-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound C=1C(C)=CC=C(N2N=CC=N2)C=1C(=O)N1CCCOC1CN(N=1)C=CC=1C1=CC=C(F)C=N1 AEZZJXJIJFSUEM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
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- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- SABRUXRTVCJNKL-UHFFFAOYSA-N 5-(4-fluorophenyl)-1,2,4-oxadiazole Chemical compound C1=CC(F)=CC=C1C1=NC=NO1 SABRUXRTVCJNKL-UHFFFAOYSA-N 0.000 claims 1
- STTNBHIFTZEPSH-UHFFFAOYSA-N 5-(4-fluorophenyl)-1h-pyrazole Chemical compound C1=CC(F)=CC=C1C1=CC=NN1 STTNBHIFTZEPSH-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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Claims (9)
1. Forbindelse gengivet ved formlen (IA):
hvor, X1 og X2 er ens eller forskellige og står for et nitrogenatom eller formlen CH; Y står for en hvilken som helst af strukturerne i følgende formelgruppe (a):
n står for 1 eller 2; R1 står for et hydrogenatom, et halogenatom eller en Ci-6-alkylgruppe; R2 står for en triazolylgruppe, en pyridylgruppe eller en pyrimidinylgruppe; R3 står for et hydrogenatom, et halogenatom eller en Ci-6-alkylgruppe, hvor Ci-6-alkylgruppen eventuelt kan være substitueret med 1 til 3 halogenatomer; og R4 står for et hydrogenatom eller en Ci-6-alkylgruppe; eller et farmaceutisk acceptabelt salt deraf.
2. Forbindelse eller et farmaceutisk acceptabelt salt deraf ifølge krav 1, hvor det i ovenanførte formel (IA) gælder, at R2 er en triazolylgruppe eller en pyrimidinylgruppe; og R3 er et halogenatom.
3. Forbindelse eller et farmaceutisk acceptabelt salt deraf ifølge krav 1 eller 2, hvor n i den ovenanførte formel (IA) er 2.
4. Forbindelse eller et farmaceutisk acceptabelt salt deraf ifølge krav 1 gengivet ved formlen (I):
hvor, X1 og X2 er ens eller forskellige og står for et nitrogenatom eller formlen CH; den ene af Y1 og Y2 står for et nitrogenatom, og den anden står for CH; n står for 1 eller 2; R1 står for et hydrogenatom, et halogenatom eller en Ci-e-alkylgruppe; R2 står for en triazolylgruppe, en pyridylgruppe eller en pyrimidinylgruppe; R3 står for et hydrogenatom, et halogenatom eller en Ci-6-alkylgruppe, hvor Ci-6-alkylgruppen eventuelt kan være substitueret med 1 til 3 halogenatomer; og R4 står for et hydrogenatom eller en Ci-6-alkylgruppe; eller et farmaceutisk acceptabelt salt deraf.
5. Forbindelse eller et farmaceutisk acceptabelt salt deraf ifølge krav 4, hvor det i den ovenanførte formel (I) gælder, at R2 er en triazolylgruppe eller en pyrimidinylgruppe; og R3 er et halogenatom.
6. Forbindelse eller et farmaceutisk acceptabelt salt deraf ifølge krav 4 eller 5, hvor n i den ovenanførte formel (I) er 2.
7. Forbindelse eller et farmaceutisk acceptabelt salt deraf ifølge krav 1, som er en specie eller en blanding af to eller flere specier udvalgt blandt: (-)-(2-{[3-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-l,3-oxazolidin-3-yl)[5-methyl-2- (2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-(2-{[4-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-l,3-oxazolidin-3-yl)[5-methyl-2- (2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-(2-{[3-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-l,3-oxazinan-3-yl)[5-methyl-2- (2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-(2-{[4-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl>-l,3-oxazinan-3-yl)[5-methyl-2- (2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[(2S,5S)-2-{[4-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-5-methyl-l,3-oxazolidin- 3-yl][5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[(2S,5R)-2-{[4-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-5-methyl-l,3-oxazolidin- 3-yl][5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, [(2S,4R)-2-{[3-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-4-methyl-l,3-oxazolidin-3- yl][5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[(2S,4S)-2-{[3-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-4-methyl-l,3-oxazolidin- 3-yl][5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, (±)-2-{[3-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl] methyl }-l,3-oxazolidin-3-yl][5-methyl-2-(pyrimidin-2-yl)phenyl]methanon, (±)-(2-{[3-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-l,3-oxazolidin-3-yl)[5-fluor-2- (pyrimidin-2-yl)phenyl]methanon, (±)-(2-{[3-(4-fluorphenyl)-lH-pyrazol-l-yl] methyl}-!,3-oxazolidin-3-yl)[5-methyl-2-(2H- 1.2.3- triazol-2-yl)phenyl]methanon, (±)-(2-{[4-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl}-l,3-oxazolidin-3-yl)[5-methyl-2-(2H- 1.2.3- triazol-2-yl)phenyl]methanon, (±)-(2-{[4-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl}-l,3-oxazolidin-3-yl)[5-methyl-2- (pyrimidin-2-yl)phenyl]methanon, (-)-(2-{{[3-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl>-l,3-oxazolidin-3-yl)[6-methyl-3-(2H- 1.2) 3-triazol-2-yl)pyridin-2-yl]methanon, (-)-(2-{[3-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl}-l,3-oxazinan-3-yl)[6-methyl-3-(2H- 1.2) 3-triazol-2-yl)pyridin-2-yl]methanon, (-)-(2-{[3-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl}-l,3-oxazinan-3-yl)[6-methyl-3- (pyrimidin-2-yl)pyridin-2-yl]methanon, (-)-(2-{[3-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-l,3-oxazinan-3-yl)[5-fluor-2-(2H- l,2(3-triazol-2-yl)phenyl]methanon, (^-^-{^-(S-fluorpyridin^-yO-lH-pyrazol-l-ylJmethylJ-l^-oxazinan-S-yOCS-methyl^- (pyrimidin-2-yl)phenyl]methanon, (-)-(2-{[4-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl}-l,3-oxazinan-3-yl)[6-methyl-3-(2H- 1.2.3- triazol-2-yl)pyridin-2-yl]methanon, (-)-(2-{[4-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl}-l,3-oxazinan-3-yl)[6-methyl-3- (pyrimidin-2-yl)pyridin-2-yl]methanon, (-)'[2-{[3-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl>-l,3-oxazinan-3-yl][5-fluor-2- (pyrimidin-2-yl)phenyl]methanon, (-)-[2-{[4-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl>-l,3-oxazinan-3-yl][5-methyl-2-(2H- l,2(3-triazol-2-yl)phenyl]methanon, (-)-[2-{[5-(5-fluorpyridin-2-yl)-l,2,4-oxadiazol-3-yl]methyl>-l,3-oxazinan-3-yl][5- methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, ()-[2-{ [5-(4-fluorphenyl)-1,2,4-oxadiazol-3-yl] methyl}-l,3-oxazinan-3-yl] [5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[2-{[5-(4-fluorphenyl)-l,2,4-oxadiazol-3-yl]methyl>-l,3-oxazinan-3-yl][6-methyl-3- (2H-l,2,3-triazol-2-yl)pyridin-2-yl]methanon, [(2S,4S)-2-{[4-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-4-methyl-l,3-oxazinan-3- yl[5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[(2S*,5S*)-2-{[4-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-5-methyl-l,3- oxazinan-3-yl][5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[2-{[3-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl)-l,3-oxazinan-3-yl][5-methyl-2- (pyrimidin-2-yl)phenyl]methanon, (±)-[2-{[l-(5-fluorpyridin-2-yl)-lH-pyrazol-4-yl] methyl }-l,3-oxazinan-3-yl][5-methyl-2-(pyrimidin-2-yl)phenyl]methanon, ()'[2-{[4-(4-fluorphenyl)-lH-pyrazol-l-yl]methyl>-l,3-oxazlnan-3-yl][5-methyl-2- (pyrimidin-2-yl)phenyl]methanon, (-)-[2-< [ l-(5-fluorpyridin-2-yl)-1 H-pyrazol-4-yl] methyl}-l,3-oxazinan-3-yl][5-fluor-2-(pyrimidin-2-yl)phenyl]methanon, (-)-[2-[l-(5-fluorpyridin-2-yl)-lH-pyrazol-3-yl]methyl}-l,3-oxazolidin-3-yl][5-methyl-2- (2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[2-{[l-(5-fluorpyridin-2-yl)-lH-pyrazol-4-yl] methyl}-l,3-oxazolidin-3-yl][5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[2-{[l-(5-fluorpyridin-2-yl)-lH-pyrazol-4-yl] methyl}-l,3-oxazinan-3-yl][5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon, (-)-[(2S*,5R*)-2-{[4-(5-fluorpyridin-2-yl)-lH-pyrazol-l-yl]methyl}-5-methyl-l,3- oxazinan-3-yl][5-methyl-2-(2H-l,2,3-triazol-2-yl)phenyl]methanon.
8. Farmaceutisk sammensætning indeholdende forbindelsen eller et acceptabelt salt deraf ifølge et hvilket som helst af kravene 1 til 7 som virksom bestanddel.
9. Lægemiddel indeholdende forbindelsen eller et farmaceutisk acceptabelt salt deraf ifølge et hvilket som helst af kravene 1 til 7 som virksom bestanddel til anvendelse i behandling eller forebyggelse af en sygdom såsom søvnforstyrrelse, depression, angstlidelse, panisk forstyrrelse, skizofreni, stofafhængighed, Alzheimers sygdom, Parkinsons sygdom, Huntingtons sygdom, spiseforstyrrelse, hovedpine, migræne, smerte, mave-tarm-sygdom, epilepsi, inflammation, immunologisk sygdom, endokrin sygdom eller forhøjet blodtryk.
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