HRP20160647T1 - Novi heterociklički derivati i njihova uporaba u liječenju neuroloških poremećaja - Google Patents
Novi heterociklički derivati i njihova uporaba u liječenju neuroloških poremećaja Download PDFInfo
- Publication number
- HRP20160647T1 HRP20160647T1 HRP20160647TT HRP20160647T HRP20160647T1 HR P20160647 T1 HRP20160647 T1 HR P20160647T1 HR P20160647T T HRP20160647T T HR P20160647TT HR P20160647 T HRP20160647 T HR P20160647T HR P20160647 T1 HRP20160647 T1 HR P20160647T1
- Authority
- HR
- Croatia
- Prior art keywords
- amino
- pyridin
- amide
- dihydro
- oxazin
- Prior art date
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- 208000012902 Nervous system disease Diseases 0.000 title 1
- 208000025966 Neurological disease Diseases 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims 24
- 125000004414 alkyl thio group Chemical group 0.000 claims 24
- 150000001875 compounds Chemical class 0.000 claims 21
- 150000003839 salts Chemical class 0.000 claims 21
- -1 cyano, amino Chemical group 0.000 claims 19
- 229910052739 hydrogen Inorganic materials 0.000 claims 17
- 239000001257 hydrogen Substances 0.000 claims 17
- 125000001424 substituent group Chemical group 0.000 claims 16
- 125000003545 alkoxy group Chemical group 0.000 claims 15
- 229910052736 halogen Inorganic materials 0.000 claims 11
- 150000002367 halogens Chemical class 0.000 claims 11
- 150000001408 amides Chemical class 0.000 claims 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 9
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 8
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 8
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 125000004043 oxo group Chemical group O=* 0.000 claims 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 5
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 5
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- 125000002947 alkylene group Chemical group 0.000 claims 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims 4
- 125000001153 fluoro group Chemical group F* 0.000 claims 4
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 3
- PFENLEKZZJZJBJ-UHFFFAOYSA-N 5-cyano-3-methylpyridine-2-carboxylic acid Chemical compound CC1=CC(C#N)=CN=C1C(O)=O PFENLEKZZJZJBJ-UHFFFAOYSA-N 0.000 claims 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 2
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- RYKZGTYZYNIIMK-UHFFFAOYSA-N 3-amino-5-(2-methoxyethyl)pyrrolo[2,3-b]pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=C(N)N=C2N(CCOC)C=CC2=N1 RYKZGTYZYNIIMK-UHFFFAOYSA-N 0.000 claims 1
- FKENLPZVPNVYQW-DLBZAZTESA-N 3-amino-n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(2,2,2-trifluoroethoxy)pyrazine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=NC(OCC(F)(F)F)=CN=2)N)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 FKENLPZVPNVYQW-DLBZAZTESA-N 0.000 claims 1
- WBCXJAZBPSKARJ-VQTJNVASSA-N 3-amino-n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(2,2-difluoroethyl)pyrrolo[2,3-b]pyrazine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=NC=3N(CC(F)F)C=CC=3N=2)N)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 WBCXJAZBPSKARJ-VQTJNVASSA-N 0.000 claims 1
- MMFYRHYCSIOPDG-LEWJYISDSA-N 3-amino-n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(2-methoxyethyl)pyrrolo[2,3-b]pyrazine-2-carboxamide Chemical compound NC=1N=C2N(CCOC)C=CC2=NC=1C(=O)NC(N=1)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 MMFYRHYCSIOPDG-LEWJYISDSA-N 0.000 claims 1
- JKHHBPZBBWGXHT-RBUKOAKNSA-N 3-amino-n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(3-fluoropropoxy)pyrazine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=NC(OCCCF)=CN=2)N)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 JKHHBPZBBWGXHT-RBUKOAKNSA-N 0.000 claims 1
- HUQALVJHHCENTE-JKSUJKDBSA-N 3-amino-n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(trifluoromethyl)pyrazine-2-carboxamide Chemical group N=1C(NC(=O)C=2C(=NC(=CN=2)C(F)(F)F)N)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 HUQALVJHHCENTE-JKSUJKDBSA-N 0.000 claims 1
- MWIIPGZITGHTPU-ZWKOTPCHSA-N 3-amino-n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(=CN=2)C#N)N)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 MWIIPGZITGHTPU-ZWKOTPCHSA-N 0.000 claims 1
- FFRBKRVVRVORIQ-DLBZAZTESA-N 3-amino-n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-(2,2,2-trifluoroethoxy)pyrazine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C(=NC(OCC(F)(F)F)=CN=2)N)=NC=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 FFRBKRVVRVORIQ-DLBZAZTESA-N 0.000 claims 1
- QLMSSDKIDFGJDT-ZWKOTPCHSA-N 3-amino-n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C(=CC(=CN=2)C#N)N)=NC=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 QLMSSDKIDFGJDT-ZWKOTPCHSA-N 0.000 claims 1
- FKENLPZVPNVYQW-UHFFFAOYSA-N 3-amino-n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(2,2,2-trifluoroethoxy)pyrazine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=NC(OCC(F)(F)F)=CN=2)N)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 FKENLPZVPNVYQW-UHFFFAOYSA-N 0.000 claims 1
- JKHHBPZBBWGXHT-UHFFFAOYSA-N 3-amino-n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(3-fluoropropoxy)pyrazine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=NC(OCCCF)=CN=2)N)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 JKHHBPZBBWGXHT-UHFFFAOYSA-N 0.000 claims 1
- HUQALVJHHCENTE-UHFFFAOYSA-N 3-amino-n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(trifluoromethyl)pyrazine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=NC(=CN=2)C(F)(F)F)N)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 HUQALVJHHCENTE-UHFFFAOYSA-N 0.000 claims 1
- MWIIPGZITGHTPU-UHFFFAOYSA-N 3-amino-n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(=CN=2)C#N)N)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 MWIIPGZITGHTPU-UHFFFAOYSA-N 0.000 claims 1
- FFRBKRVVRVORIQ-UHFFFAOYSA-N 3-amino-n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-(2,2,2-trifluoroethoxy)pyrazine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C(=NC(OCC(F)(F)F)=CN=2)N)=NC=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 FFRBKRVVRVORIQ-UHFFFAOYSA-N 0.000 claims 1
- QLMSSDKIDFGJDT-UHFFFAOYSA-N 3-amino-n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C(=CC(=CN=2)C#N)N)=NC=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 QLMSSDKIDFGJDT-UHFFFAOYSA-N 0.000 claims 1
- NHQRPMDOQOKWPU-UHFFFAOYSA-N 3-chloro-5-cyanopyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC=C(C#N)C=C1Cl NHQRPMDOQOKWPU-UHFFFAOYSA-N 0.000 claims 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 1
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- QONFJNGJOVKPCS-QZTJIDSGSA-N N-[4-[(3S,6R)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2H-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-(difluoromethoxy)pyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC(OC(F)F)=CN=2)Cl)=NC=C(F)C=1[C@@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 QONFJNGJOVKPCS-QZTJIDSGSA-N 0.000 claims 1
- IKGBDDRQPRQHRS-ZVAWYAOSSA-N N-[5-[(3R)-5-amino-3-(difluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]-5-fluoro-4H-pyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound NC1=N[C@@](COC1)(C(F)F)C1(CC=C(N=C1)NC(=O)C1=NC=C(C=C1C)C#N)F IKGBDDRQPRQHRS-ZVAWYAOSSA-N 0.000 claims 1
- GNUVJSLVOMHUKV-OMKBGSMGSA-N N-[6-[(3R,6R)-2-amino-3,6-dimethyl-6-(trifluoromethyl)-2H-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical group NC1O[C@](C=N[C@]1(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1C)C#N)F)(C(F)(F)F)C GNUVJSLVOMHUKV-OMKBGSMGSA-N 0.000 claims 1
- MGXZYVPDNLXFNB-YVDXPPGISA-N N-[6-[(3R,6R)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2H-1,4-oxazin-3-yl]pyridin-2-yl]-5-chloro-4,6-dideuterio-3-(trideuteriomethyl)pyridine-2-carboxamide Chemical compound [2H]c1nc(C(=O)Nc2cccc(n2)[C@]2(C)CO[C@](C)(C(N)=N2)C(F)(F)F)c(c([2H])c1Cl)C([2H])([2H])[2H] MGXZYVPDNLXFNB-YVDXPPGISA-N 0.000 claims 1
- JOPVCLNERIBRRX-UHFFFAOYSA-N N-[6-[6-amino-3-(fluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]pyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound NC1C=NC(CO1)(CF)C1=CC=CC(=N1)NC(=O)C1=NC=C(C=C1C)C#N JOPVCLNERIBRRX-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000008186 active pharmaceutical agent Substances 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 208000010877 cognitive disease Diseases 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical group OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000012907 medicinal substance Substances 0.000 claims 1
- ZDOMSYMJUOFARG-IBGZPJMESA-N n-[4-[(3r)-5-amino-6,6-bis(fluoromethyl)-3-methyl-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC([C@@]2(C)N=C(N)C(CF)(CF)OC2)=C(F)C=N1 ZDOMSYMJUOFARG-IBGZPJMESA-N 0.000 claims 1
- RPVSVZJNXFHPNA-ZWKOTPCHSA-N n-[4-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=NC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 RPVSVZJNXFHPNA-ZWKOTPCHSA-N 0.000 claims 1
- VAFUDQUXHDFJQT-RBUKOAKNSA-N n-[4-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC([C@@]2(C)N=C(N)[C@@](C)(OC2)C(F)(F)F)=C(F)C=N1 VAFUDQUXHDFJQT-RBUKOAKNSA-N 0.000 claims 1
- VAFUDQUXHDFJQT-RTBURBONSA-N n-[4-[(3s,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC([C@]2(C)N=C(N)[C@@](C)(OC2)C(F)(F)F)=C(F)C=N1 VAFUDQUXHDFJQT-RTBURBONSA-N 0.000 claims 1
- QONFJNGJOVKPCS-UHFFFAOYSA-N n-[4-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-(difluoromethoxy)pyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC(OC(F)F)=CN=2)Cl)=NC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 QONFJNGJOVKPCS-UHFFFAOYSA-N 0.000 claims 1
- RPVSVZJNXFHPNA-UHFFFAOYSA-N n-[4-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=NC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 RPVSVZJNXFHPNA-UHFFFAOYSA-N 0.000 claims 1
- VAFUDQUXHDFJQT-UHFFFAOYSA-N n-[4-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC(C2(C)N=C(N)C(C)(OC2)C(F)(F)F)=C(F)C=N1 VAFUDQUXHDFJQT-UHFFFAOYSA-N 0.000 claims 1
- OLVSRIFVQCSRTD-VXYOWKKLSA-N n-[4-[5-amino-3-(fluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]pyridin-2-yl]-5-chloro-4,6-dideuterio-3-(trideuteriomethyl)pyridine-2-carboxamide Chemical compound [2H]C1=C(Cl)C([2H])=NC(C(=O)NC=2N=CC=C(C=2)C2(CF)N=C(N)COC2)=C1C([2H])([2H])[2H] OLVSRIFVQCSRTD-VXYOWKKLSA-N 0.000 claims 1
- GPJQSUWRIBDPMP-UHFFFAOYSA-N n-[4-[5-amino-3-(fluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]pyridin-2-yl]-5-chloropyridine-2-carboxamide Chemical compound C1OCC(N)=NC1(CF)C1=CC=NC(NC(=O)C=2N=CC(Cl)=CC=2)=C1 GPJQSUWRIBDPMP-UHFFFAOYSA-N 0.000 claims 1
- ZDOMSYMJUOFARG-UHFFFAOYSA-N n-[4-[5-amino-6,6-bis(fluoromethyl)-3-methyl-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC(C2(C)N=C(N)C(CF)(CF)OC2)=C(F)C=N1 ZDOMSYMJUOFARG-UHFFFAOYSA-N 0.000 claims 1
- IZGSDQIFBJRHBB-UHFFFAOYSA-N n-[5-[5-amino-3-(fluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]-6-chloropyridin-3-yl]-5-bromopyridine-2-carboxamide Chemical compound C1OCC(N)=NC1(CF)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CN=C1Cl IZGSDQIFBJRHBB-UHFFFAOYSA-N 0.000 claims 1
- WQUQHUCOJVZXJC-UHFFFAOYSA-N n-[6-(5-amino-3-methyl-2,6-dihydro-1,4-oxazin-3-yl)pyridin-2-yl]-5-bromopyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2N=CC(Br)=CC=2)=NC=1C1(C)COCC(N)=N1 WQUQHUCOJVZXJC-UHFFFAOYSA-N 0.000 claims 1
- LVXIXHYWPFXDKS-KRWDZBQOSA-N n-[6-[(3r)-5-amino-3-(difluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound C1OCC(N)=N[C@]1(C(F)F)C1=NC(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=CC=C1F LVXIXHYWPFXDKS-KRWDZBQOSA-N 0.000 claims 1
- WQUQHUCOJVZXJC-INIZCTEOSA-N n-[6-[(3r)-5-amino-3-methyl-2,6-dihydro-1,4-oxazin-3-yl]pyridin-2-yl]-5-bromopyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2N=CC(Br)=CC=2)=NC=1[C@]1(C)COCC(N)=N1 WQUQHUCOJVZXJC-INIZCTEOSA-N 0.000 claims 1
- DRKAFGKWERJHKK-DLBZAZTESA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3,5-dichloropyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(Cl)=CN=2)Cl)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 DRKAFGKWERJHKK-DLBZAZTESA-N 0.000 claims 1
- NHQMQCNPITZLAA-ZWKOTPCHSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3,5-dimethylpyrazine-2-carboxamide Chemical compound CC1=NC(C)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(C)N=C(N)[C@@](C)(OC2)C(F)(F)F)=N1 NHQMQCNPITZLAA-ZWKOTPCHSA-N 0.000 claims 1
- LHTZVIDMVHFLLF-ZWKOTPCHSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 LHTZVIDMVHFLLF-ZWKOTPCHSA-N 0.000 claims 1
- UYFPRMQOSKPOQR-JKSUJKDBSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-4-chloro-1-(difluoromethyl)pyrazole-3-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CN(N=2)C(F)F)Cl)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 UYFPRMQOSKPOQR-JKSUJKDBSA-N 0.000 claims 1
- IEGJECJTLOSIQV-RBUKOAKNSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(difluoromethoxy)-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(OC(F)F)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(C)N=C(N)[C@@](C)(OC2)C(F)(F)F)=N1 IEGJECJTLOSIQV-RBUKOAKNSA-N 0.000 claims 1
- VZKUTAXMEIXBFQ-RBUKOAKNSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(fluoromethoxy)-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(OCF)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(C)N=C(N)[C@@](C)(OC2)C(F)(F)F)=N1 VZKUTAXMEIXBFQ-RBUKOAKNSA-N 0.000 claims 1
- PWIJFDYDPIMSCV-RBUKOAKNSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-methoxy-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(OC)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(C)N=C(N)[C@@](C)(OC2)C(F)(F)F)=N1 PWIJFDYDPIMSCV-RBUKOAKNSA-N 0.000 claims 1
- QEEWKGAHKUUMAX-DLBZAZTESA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-methylpyrazine-2-carboxamide Chemical compound C1=NC(C)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(C)N=C(N)[C@@](C)(OC2)C(F)(F)F)=N1 QEEWKGAHKUUMAX-DLBZAZTESA-N 0.000 claims 1
- KKRXTJDWKWWIKU-LEWJYISDSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-6-chloro-1-(2,2-difluoroethyl)pyrrolo[3,2-b]pyridine-5-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC=3N(CC(F)F)C=CC=3N=2)Cl)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 KKRXTJDWKWWIKU-LEWJYISDSA-N 0.000 claims 1
- LUTGKRKBQRZCOA-FCHUYYIVSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-6-chloro-1-(2-methoxyethyl)pyrrolo[3,2-b]pyridine-5-carboxamide Chemical compound ClC=1C=C2N(CCOC)C=CC2=NC=1C(=O)NC(N=1)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 LUTGKRKBQRZCOA-FCHUYYIVSA-N 0.000 claims 1
- VANDNQQVYPKEOC-DLBZAZTESA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-bromo-3-chloropyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C(=CC(Br)=CN=2)Cl)=NC=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 VANDNQQVYPKEOC-DLBZAZTESA-N 0.000 claims 1
- QSCBNUCKFXAIJL-ZWKOTPCHSA-N n-[6-[(3r,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2N=CC(=CC=2)C#N)=NC=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 QSCBNUCKFXAIJL-ZWKOTPCHSA-N 0.000 claims 1
- LHTZVIDMVHFLLF-QZTJIDSGSA-N n-[6-[(3s,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=CC=C(F)C=1[C@@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 LHTZVIDMVHFLLF-QZTJIDSGSA-N 0.000 claims 1
- MTNQDQUYJFDVLS-RTBURBONSA-N n-[6-[(3s,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC=C(F)C([C@]2(C)N=C(N)[C@@](C)(OC2)C(F)(F)F)=N1 MTNQDQUYJFDVLS-RTBURBONSA-N 0.000 claims 1
- QSCBNUCKFXAIJL-QZTJIDSGSA-N n-[6-[(3s,6r)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2N=CC(=CC=2)C#N)=NC=1[C@@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 QSCBNUCKFXAIJL-QZTJIDSGSA-N 0.000 claims 1
- NHQMQCNPITZLAA-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3,5-dimethylpyrazine-2-carboxamide Chemical compound CC1=NC(C)=CN=C1C(=O)NC1=CC=C(F)C(C2(C)N=C(N)C(C)(OC2)C(F)(F)F)=N1 NHQMQCNPITZLAA-UHFFFAOYSA-N 0.000 claims 1
- DOJQNRYLSRMQDA-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-(difluoromethoxy)pyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(OC(F)F)=CN=2)Cl)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 DOJQNRYLSRMQDA-UHFFFAOYSA-N 0.000 claims 1
- PSBBWFNMHDUTRH-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-(trifluoromethyl)pyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(=CN=2)C(F)(F)F)Cl)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 PSBBWFNMHDUTRH-UHFFFAOYSA-N 0.000 claims 1
- LHTZVIDMVHFLLF-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 LHTZVIDMVHFLLF-UHFFFAOYSA-N 0.000 claims 1
- UYFPRMQOSKPOQR-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-4-chloro-1-(difluoromethyl)pyrazole-3-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CN(N=2)C(F)F)Cl)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 UYFPRMQOSKPOQR-UHFFFAOYSA-N 0.000 claims 1
- IEGJECJTLOSIQV-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(difluoromethoxy)-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(OC(F)F)=CN=C1C(=O)NC1=CC=C(F)C(C2(C)N=C(N)C(C)(OC2)C(F)(F)F)=N1 IEGJECJTLOSIQV-UHFFFAOYSA-N 0.000 claims 1
- VZKUTAXMEIXBFQ-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-(fluoromethoxy)-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(OCF)=CN=C1C(=O)NC1=CC=C(F)C(C2(C)N=C(N)C(C)(OC2)C(F)(F)F)=N1 VZKUTAXMEIXBFQ-UHFFFAOYSA-N 0.000 claims 1
- MTNQDQUYJFDVLS-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC=C(F)C(C2(C)N=C(N)C(C)(OC2)C(F)(F)F)=N1 MTNQDQUYJFDVLS-UHFFFAOYSA-N 0.000 claims 1
- PWIJFDYDPIMSCV-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-methoxy-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(OC)=CN=C1C(=O)NC1=CC=C(F)C(C2(C)N=C(N)C(C)(OC2)C(F)(F)F)=N1 PWIJFDYDPIMSCV-UHFFFAOYSA-N 0.000 claims 1
- QEEWKGAHKUUMAX-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-methylpyrazine-2-carboxamide Chemical compound C1=NC(C)=CN=C1C(=O)NC1=CC=C(F)C(C2(C)N=C(N)C(C)(OC2)C(F)(F)F)=N1 QEEWKGAHKUUMAX-UHFFFAOYSA-N 0.000 claims 1
- LUTGKRKBQRZCOA-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-6-chloro-1-(2-methoxyethyl)pyrrolo[3,2-b]pyridine-5-carboxamide Chemical compound ClC=1C=C2N(CCOC)C=CC2=NC=1C(=O)NC(N=1)=CC=C(F)C=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 LUTGKRKBQRZCOA-UHFFFAOYSA-N 0.000 claims 1
- DPIDWDAWIQYLLV-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=NC=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 DPIDWDAWIQYLLV-UHFFFAOYSA-N 0.000 claims 1
- VANDNQQVYPKEOC-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-bromo-3-chloropyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C(=CC(Br)=CN=2)Cl)=NC=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 VANDNQQVYPKEOC-UHFFFAOYSA-N 0.000 claims 1
- MGXZYVPDNLXFNB-ZXZAAQOOSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-chloro-4,6-dideuterio-3-(trideuteriomethyl)pyridine-2-carboxamide Chemical compound [2H]C1=C(Cl)C([2H])=NC(C(=O)NC=2N=C(C=CC=2)C2(C)N=C(N)C(C)(OC2)C(F)(F)F)=C1C([2H])([2H])[2H] MGXZYVPDNLXFNB-ZXZAAQOOSA-N 0.000 claims 1
- QSCBNUCKFXAIJL-UHFFFAOYSA-N n-[6-[5-amino-3,6-dimethyl-6-(trifluoromethyl)-2h-1,4-oxazin-3-yl]pyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2N=CC(=CC=2)C#N)=NC=1C1(C)COC(C)(C(F)(F)F)C(N)=N1 QSCBNUCKFXAIJL-UHFFFAOYSA-N 0.000 claims 1
- LVXIXHYWPFXDKS-UHFFFAOYSA-N n-[6-[5-amino-3-(difluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound C1OCC(N)=NC1(C(F)F)C1=NC(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=CC=C1F LVXIXHYWPFXDKS-UHFFFAOYSA-N 0.000 claims 1
- GIKOSRRRDYUWLE-UHFFFAOYSA-N n-[6-[5-amino-3-(difluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC=C(F)C(C2(N=C(N)COC2)C(F)F)=N1 GIKOSRRRDYUWLE-UHFFFAOYSA-N 0.000 claims 1
- HBAGGGIQIJILPN-UHFFFAOYSA-N n-[6-[5-amino-3-(fluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]pyridin-2-yl]-5-bromopyridine-2-carboxamide Chemical compound C1OCC(N)=NC1(CF)C1=CC=CC(NC(=O)C=2N=CC(Br)=CC=2)=N1 HBAGGGIQIJILPN-UHFFFAOYSA-N 0.000 claims 1
- RWYPCDYBONWERI-UHFFFAOYSA-N n-[6-[5-amino-3-(fluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]pyridin-2-yl]-5-carbamothioylpyridine-2-carboxamide Chemical compound N1=CC(C(=S)N)=CC=C1C(=O)NC1=CC=CC(C2(CF)N=C(N)COC2)=N1 RWYPCDYBONWERI-UHFFFAOYSA-N 0.000 claims 1
- OEZZKNFURPODDF-GGCIUVQJSA-N n-[6-[5-amino-3-(fluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]pyridin-2-yl]-5-chloro-4,6-dideuterio-3-(trideuteriomethyl)pyridine-2-carboxamide Chemical compound [2H]C1=C(Cl)C([2H])=NC(C(=O)NC=2N=C(C=CC=2)C2(CF)N=C(N)COC2)=C1C([2H])([2H])[2H] OEZZKNFURPODDF-GGCIUVQJSA-N 0.000 claims 1
- CDJHOYHFBRGWII-UHFFFAOYSA-N n-[6-[5-amino-3-(fluoromethyl)-2,6-dihydro-1,4-oxazin-3-yl]pyridin-2-yl]-5-chloropyridine-2-carboxamide Chemical compound C1OCC(N)=NC1(CF)C1=CC=CC(NC(=O)C=2N=CC(Cl)=CC=2)=N1 CDJHOYHFBRGWII-UHFFFAOYSA-N 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- PSBBWFNMHDUTRH-DLBZAZTESA-N umibecestat Chemical group N=1C(NC(=O)C=2C(=CC(=CN=2)C(F)(F)F)Cl)=CC=C(F)C=1[C@]1(C)CO[C@@](C)(C(F)(F)F)C(N)=N1 PSBBWFNMHDUTRH-DLBZAZTESA-N 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
Claims (21)
1. Spoj, naznačen time, da ima formulu (I), ili njegova farmaceutski prihvatljiva sol,
[image]
u kojoj
X1 je CR1 ili N;
X3 je CR3 ili N;
X4 je CR4 ili N;
X5 je CR5;
pri čemu jedan i ne više od jednoga od X1, X3 i X4 je N;
R1 je vodik;
R2 je aril, heteroaril-skupina ili nearomatska heterociklička skupina G1, gdje je ta G1-skupina opcijski supstituirana s 1, 2, 3 ili 4 supstituenta neovisno odabrana iz skupine koju čine: cijano, amino, amino-(C1-8)alkil, N-(C1-4)alkil-amino-(C1-8)alkil, N,N-di(C1-4)alkil-amino-(C1-8)alkil, aminokarbonil, tiokarbamoil, halogen, (C1-8)alkil, halogen-(C1-8)alkil, hidroksi, okso, (C1-8)alkoksi , halogen-
(C1-8)alkoksi, (C1-8)alkiltio, halogen-(C1-8)alkiltio, (C1-8)alkoksi-(C1-8)alkil,
(C3-8)cikloalkil-(C1-8)alkoksi, (C1-8)alkoksi-(C1-8)alkoksi, (C1-8)alkoksi-(C1-8)alkiltio, (C1-8)alkiltio-(C1-8)alkil, (C1-8) alkiltio-(C1-8)alkoksi, (C1-8)alkiltio-(C1-8)alkiltio,
(C2-8)alkenil, (C2-8)alkinil, (C2-8)alkenoksi, (C2-8)alkinoksi, te
(C3-8)cikloalkil , aril, heteroaril ili nearomatska heterociklička skupina G2,
gdje je ta G2-skupina opcijski supstituirana s 1, 2, 3 ili 4 supstituenta neovisno odabrana iz skupine koju čine: cijano, aminokarbonil, halogen, (C1-8)alkil,
halogen-(C1-8)alkil, hidroksi, (C1-8)akoksi, halogen-(C1-8)alkoksi, (C1-8)alkiltio, halogen-(C1-8)alkiltio, (C1-8)alkoksi-(C1-8)alkil, (C1-8)alkoksi-(C1-8)alkoksi,
(C1-8)alkoksi-(C1-8)alkiltio, (C1-8)alkiltio-(C1-8)alkil, (C1-8)alkiltio-(C1-8)alkoksi,
(C1-8)alkiltio-(C1-8)alkiltio, (C2-8)alkenil i (C2-8)alkinil;
R3 je vodik;
R4je vodik, cijano, halogen, (C1-8)alkil, halogen-(C1-8)alkil, (C1-8)alkoksi,
halogen-(C1-8)alkoksi, (C1-8)alkiltio, halogen-(C1-8)alkiltio, (C1-8)alkoksi-(C1-8)alkil,
(C1-8)alkoksi-(C1-8)alkoksi, (C1-8)alkoksi-(C1-8)alkiltio, (C1-8)alkiltio-(C1-8)alkil,
(C1-8)alkiltio-(C1-8)alkoksi, (C1-8)alkiltio-(C1-8)alkiltio , (C2-8)alkenil ili (C2-8)alkinil;
R5 je vodik, cijano, halogen, (C1-8)alkil, halogen-(C1-8)alkil, (C1-8)alkoksi, halogen-(C1-8)alkoksi, (C1-8)alkiltio, halogen-(C1-8)alkiltio, (C1-8)alkoksi-(C1-8)alkil, (C1-8)alkoksi-(C1-8)alkoksi, (C1-8)alkoksi-(C1-8)alkiltio, (C1-8)alkiltio-(C1-8)alkil,
(C1-8)alkiltio-(C1-8)alkoksi, (C1-8)alkiltio-(C1-8)alkiltio, (C2-8)alkenil ili (C2-8)alkinil;
ili
kada se R4 i R5 uzimaju zajedno, tada su -C(H)=C(H)-C(H)=C(H)- ili
(C1-8)alkilen-skupina, gdje su u toj (C1-8)alkilen-skupini jedan ili dva
-CH2-člana prstena opcijski zamijenjeni s hetero-članovima prstena neovisno odabranima iz skupine koju čine: -N(H)-, N[(C1-8)alkil]-, -O-,
-S-, -S(=O)- ili -S(=O)2-;
R6 je (C1-8)alkil, halogen-(C1-6)alkil, hidroksi-(C1-8)alkil, (C1-8)alkoksi-(C1-8)alkil, merkapto-(C1-8)alkil, (C1-8)alkiltio-(C1-8)alkil, amino-(C1-8)alkil, N-(C1-4)alkil-amino-
(C1-8)alkil, N,N-di(C1-4)alkil=amino-(C1-8)alkil, (C2-8)alkenil ili (C2-8)alkinil;
ili
kada se R5 i R6 uzimaju zajedno, tada su (C1-4)alkilen-skupina, gdje je u toj
(C1-4)alkilen-skupini jedan -CH2-član prstena opcijski zamijenjen s hetero-članom prstena neovisno odabranim iz skupine koju čine: N(H)-,
-N[(C1-4)alkil]-, -O-, -S-, -(=O)- ili -S(=O)2-;
E1 je -C(R7)(R8)-, gdje svaki od R7 i R8 je vodik;
E2 je -C(R11)(R12)-;
bilo da
je svaki od R11 i R12 neovisno odabran iz skupine koju čine: vodik, cijano, halogen, (C1-8)alkil, halogen-(C1-8)alkil, (C1-8)alkoksi-(C1-8)alkil i (C1-8)alkiltio-(C1-8)alkil;
ili
kada se R11 i R12 uzimaju zajedno, tada su okso ili -CR15R16-CR17R18-,
gdje su R15, R16, R17i R18 neovisno odabrani od vodika i fluora.
2. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol,
naznačen/a time, da X1 je N; X3 je CR3; X4 je CR4; i X5 je CR5.
3. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol,
naznačen/a time, da ima formulu (Ic)
[image]
u kojoj
X1 je CH ili N;
X3 je CH ili N;
X4 je CR4 ili N;
pri čemu jedan i ne više od jednoga od X1, X3 i X4 je N;
R2 je 5-člana ili 6-člana heteroaril-skupina u čijoj strukturi od 1, 2, 3 ili 4 člana prstena su hetero-članovi prstena neovisno odabrani iz skupine koja se sastoji od dušikovog člana prstena, kisikovog člana prstena i sumporovog člana prstena, gdje je ta skupina opcijski supstituirana s 1, 2, 3 ili 4 supstituenta neovisno odabrana iz skupine koju čine: cijano, amino, aminokarbonil, tiokarbamoil, halogen, (C1-4)alkil, halogen-(C1-4)alkil, hidroksi, okso, (C1-4)alkoksi, halogen-(C1-4)alkoksi, (C1-4)alkiltio, halogen-(C1-4)alkiltio , (C1-4)alkoksi-(C1-4)alkil, (C1-4)alkoksi-(C1-4)alkoksi, (C1-4)alkoksi-(C1-4)alkiltio, (C1-4)alkiltio-(C1-4)alkil,
(C1-4)alkiltio-(C1-4)alkoksi, (C1-4)alkiltio-(C1-4)alkiltio, (C2-4)alkenil, (C2-4)alkinil,
(C2-4)alkenoksi i (C2-4)alkinoksi;
R4 i R5 su neovisno odabrani iz skupine koju čine: vodik, cijano, halogen,
(C1-4)alkil, halogen-(C1-4)alkil, (C1-4)alkoksi ili halogen-(C1-4)alkoksi;
R6 je (C1-3)alkil ili fluoro-(C1-3)alkil; i
svaki od R11 i R12 je neovisno odabran iz skupine koju čine: vodik, (C1-3)alkil i halogen-(C1-3)alkil.
4. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol,
naznačen/a time, da ima formulu (Ic)
[image]
u kojoj
X1 je CH ili N;
X3 je CH ili N;
X4 je CR4 ili N;
pri čemu jedan i ne više od jednoga od X1, X3 i X4 je N;
R2 je piridil-skupina ili pirazinil-skupina, koja je opcijski supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana iz skupine koju čine: cijano, amino, aminokarbonil, tiokarbamoil, halogen, (C1-4)alkil, halogen-(C1-4)alkil, hidroksi, okso, (C1-4)alkoksi, halogen-(C1-4)alkoksi, (C1-4)alkiltio, halogen-(C1-4)alkiltio ,
(C1-4)alkoksi-(C1-4)alkil, (C1-4)alkoksi-(C1-4)alkoksi, (C1-4)alkoksi-(C1-4)alkiltio,
(C1-4)alkiltio-(C1-4)alkil, (C1-4)alkiltio-(C1-4)alkoksi, (C1-4)alkiltio-(C1-4)alkiltio,
(C2-4)alkenil, (C2-4)alkinil, (C2-4)alkenoksi i (C2-4)alkinoksi;
R4 i R5 su neovisno vodik ili halogen;
R6 je (C1-3)alkil ili fluoro-(C1-3)alkil; i
svaki od R11 i R12 je neovisno odabran iz skupine koju čine: vodik, (C1-3)alkil i fluoro-(C1-3)alkil.
5. Spoj prema bilo kojem od zahtjeva 1 do 4, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da je svaki od R11 i R12 neovisno odabran iz skupine koju čine: vodik, metil, fluorometil, difluorometil i trifluorometil.
6. Spoj prema bilo kojem od zahtjeva 1 do 5, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da R6 je metil, fluorometil, difluorometil ili trifluorometil.
7. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol,
naznačen/a time, da ima formulu (Id)
[image]
u kojoj
X1 je CH ili N;
X3 je CH ili N;
X4 je CR4 ili N;
pri čemu jedan i ne više od jednoga od X1, X3 i X4 je N;
R2 je piridil-skupina ili pirazinil-skupina koja je supstituirana s dva ili tri supstituenta te je pritom jedan od supstituenata smješten na para-poziciji i jedan od supstituenata je smješten na orto-poziciji od piridil-skupine ili pirazinil-skupine, u odnosu na amidnu poveznicu te su pritom supstituenti neovisno odabrani iz skupine koju čine: cijano, amino, halogen, (C1-4)alkil, halogen-(C1-4)alkil, hidroksi, okso, (C1-4)alkoksi i halogen-(C1-4)alkoksi;
R4 i R5 su neovisno vodik ili halogen;
R6 je metil, fluorometil, difluorometil ili trifluorometil; i
svaki od R11 i R12 je neovisno odabran iz skupine koju čine: vodik, metil, fluorometil, difluorometil i trifluorometil.
8. Spoj prema bilo kojem od zahtjeva 1 do7, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da R2 je piridin-2-il-skupina ili pirazin-2-il-skupina, koja je supstituirana s dva supstituenta i pri čemu je jedan od supstituenata smješten na para-poziciji i jedan od supstituenata je smješten na orto-poziciji od piridin-2-il-skupine ili pirazin-2-il-skupine, u odnosu na amidnu poveznicu te su pritom supstituenti neovisno odabrani iz skupine koju čine: cijano, amino, fluoro, bromo, kloro, hidroksil, okso, metil, fluorometil, difluorometil, trifluorometil, metoksi, fluorometoksi, difluorometoksi i trifluorometoksi.
9. Spoj prema bilo kojem od zahtjeva 3 do 8, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da X1 je N; X3 je CH; i X4 je CR4.
10. Spoj prema bilo kojem od zahtjeva 1 do 9, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da R4 je vodik.
11. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol,
naznačen/a time, da ima formulu (Ie)
[image]
u kojoj
R2 je piridin-2-il-skupina ili pirazin-2-il-skupina, koja je supstituirana s dva supstituenta i pri čemu je jedan od supstituenata smješten na para-poziciji i jedan od supstituenata je smješten na orto-poziciji od piridin-2-il-skupine ili pirazin-2-il-skupine, u odnosu na amidnu poveznicu te su pritom supstituenti neovisno odabrani iz skupine koju čine: cijano, amino, fluoro, bromo, kloro, hidroksil, okso, metil, fluorometil, difluorometil, trifluorometil, metoksi, fluorometoksi, difluorometoksi i trifluorometoksi;
R5 je vodik ili fluoro;
R6 je metil, fluorometil ili difluorometil; i
svaki od R11 i R12 je neovisno odabran iz skupine koju čine: vodik, metil, fluorometil, difluorometil i trifluorometil.
12. Spoj prema bilo kojem od zahtjeva 1 do 11, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da R5 je fluoro.
13. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol,
naznačen/a time, da je odabran/a iz skupine koju čine:
5-bromo-piridin-2-karboksilna kiselina-[6-(5-amino-3-metil-3,6-dihidro-2H-[1,4]-oksazin-3-il)-piridin-2-il]amid;
5-kloro-piridin-2-karboksilna kiselina-[6-(5-amino-3-fluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-bromo-piridin-2-karboksilna kiselina-[6-(5-amino-3-fluorometil-3,6-dihidro-2H[1,4]oksazin-3-il)-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[6-(6-amino-3-fluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
4,6-dideutero-5-kloro-3-trideuterometil-piridin-2-karboksilna kiselina-[6-(5-amino-3-fluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-tiokarbamoil-piridin-2-karboksilna kiselina-[6-(5-amino-3-fluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluoro-metil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-cijano-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-
trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
4,6-dideutero-5-kloro-3-trideuterometil-piridin-2-karboksilna kiselina-[4-
(5-amino-3-fluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-kloro-piridin-2-karboksilna kiselina-[4-(5-amino-3-fluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[4-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-bromo-piridin-2-karboksilna kiselina-[5-(5-amino-3-fluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-6-kloro-piridin-3-il]amid;
3-amino-5-cijano-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-
trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-
trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-kloro-4,6-dideuterio-3-trideuteriometil-piridin-2-karboksilna kiselina-
[6-(5-amin-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-bromo-3-kloro-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
3-amino-5-(2,2,2-trifluoro-etoksi)-pirazin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-metoksi-3-metil-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-(2,2,2-trifluoro-etoksi)-pirazin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-cijano-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-
trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-difluorometoksi-3-metil-piridin-2-karboksilna kiselina- [6-(5-amino-3,6-
dimetil-6-trifluorametil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]
amid;
3-kloro-5-difluorometoksi-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-
dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-
2-il]amid;
3,5-dikloro-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-fuorometoksi-3-metil-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-metil-pirazin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-kloro-5-trifluorometil-piridin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[4-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-kloro-5-difluorometoksi-piridin-2-karboksilna kiselina-[4-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-
2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[4-(5-amino-6,6-bis-fluorometil-3-metil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[6-(5-amino-3-difluorometil-
3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[6-(5-amino-3-difluorometil-
3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3,5-dimetil-pirazin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-(3-fluoropropoksi)-pirazin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-(2-metoksi-etil)-5H-pirolo[2,3-b]pirazin-2-karboksilna kiselina-
[6-((5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-trifluorometil-pirazin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]
amid;
3-amino-5-(2,2-difluoro-etil)-5H-pirolo[2,3-b]pirazin-2-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
4-kloro-1-d ifluorometil-1H-pirazol-3-karboksilna kislina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]
amid;
6-kloro-1-(2,2-difluoro-etil)-1H-pirolo[3,2-b]piridin-5-karboksilna kiselina-[6-(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid; i
6-kloro-1-(2-metoksi-etil)-1H-pirolo[3,2-b]piridin-5-karboksilna kiselina-[6(5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-
2-il]amid.
14. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol,
naznačen/a time, da je odabran/a iz skupine koju čine:
5-bromo-piridin-2-karboksilna kiselina-[6-((R)-5-amino-3-metil-3,6-dihidro-2H-[1,4]-oksazin-3-il)-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluoro-metil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-cijano-pirid in-2-karboksilna kiselina-[6-((3S,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H [1,4]oksazin-3-il)-piridin-2-il]amid;
5-cijano-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H[1,4]oksazin-3-il)-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[6-((3S,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[4-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[4-((3S,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro- 2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-cijano-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3-6-dihidro- 2H-[1,4]oksazin-3-il)-piridin-2-il]amid;
5-kloro-4,6-dideuterio-3-trideuteriometil-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-piridin-2-il]
amid;
5-bromo-3-kloro-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[ 1,4]oksazin-3-il)-pirid in-2-il]amid;
3-amino-5-(2,2,2-trifluoro-etoksi)-pirazin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H[1,4]oksazin-3-il)-piridin-2-il]
amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifuorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-metoksi-3-metil-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-(2,2,2-trifluoro-etoksi)-pirazin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-cijano-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[6-((3S,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro- 2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-difluorometoksi-3-metil-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]
amid;
3-kloro-5-difluorometoksi-piridin-2-piridin-2-karboksilna kiselina-[6-((3R,6R)-
5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3,5-dikloro-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-fluorometoksi-3-metil-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-metil-pirazin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[4-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-kloro-5-difluorometoksi-piridin-2-karboksilna kiselina-[4-((3S,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]-amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[4-((R)-5-amino-6,6-bis-fluorometil-3-metil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[5-((R)-5-amino-3-difluorometil-3,6-
dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
5-cijano-3-metil-piridin-2-karboksilna kiselina-[6H((S)-5-amino-3-difluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-kloro-5-cijano-piridin-2-karboksilna kiselina-[6-((R)-5-amino-3-difluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3,5-dimetil-pirazin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-(3-fluoro-propoksi)-pirazin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]
amid;
3-amino-5-(2-metoksi-etil)-5H-pirolo[2,3-b]pirazin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
3-amino-5-(2,2-difluoro-etil)-5H-pirolo[2,3-b]pirazin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid;
4-kloro-1-difluorometil-1H-pirazol-3-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]
amid;
6-kloro-1-(2,2-difluoro-etil)-1H-pirolo[3,2-b]piridin-5-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid; i
6-kloro-1-(2-metoksi-etil)-1H-pirolo[3,2-b]piridin-5-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid.
15. Spoj prema zahtjevu 1, naznačen time, da je to 5-cijano-3-metil-piridin-2-karboksilna kiselina-[6-((3R,6R)-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid, ili njegova farmaceutski prihvatljiva sol, koji ima sljedeću formula
[image]
16. Spoj prema zahtjevu 1, naznačen time, da je to 3-kloro-5-trifluorometil-piridin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid, ili njegova farmaceutski prihvatljiva sol, koji ima sljedeću formula
[image]
17. Spoj prema zahtjevu 1, naznačen time, da je to 3-amino-5-trifluorometil-pirazin-2-karboksilna kiselina-[6-((3R,6R)-5-amino-3,6-dimetil-6-trifluorometil-3,6-dihidro-2H-[1,4]oksazin-3-il)-5-fluoro-piridin-2-il]amid, ili njegova farmaceutski prihvatljiva sol, koji ima sljedeću formula
[image]
18. Spoj prema bilo kojem od zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da se upotrebljava kao lijek.
19. Spoj prema bilo kojem od zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da se upotrebljava u liječenju ili prevenciji Alzheimerove bolesti ili umjerenog kognitivnog oštećenja.
20. Farmaceutski pripravak, naznačen time, da obuhvaća spoj prema bilo kojem od zahtjeva 1 do 17, ili njegovu farmaceutski prihvatljivu sol, kao djelatni farmaceutski sastojak udružen s najmanje jednim farmaceutski prihvatljivim nosačem ili razrjeđivačem.
21. Farmaceutska kombinacija, naznačena time, da obuhvaća terapeutski učinkovitu količinu spoja prema bilo kojem od zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli, te neku drugu ljekovitu tvar, za istovremenu ili uzastopnu primjenu.
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Families Citing this family (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103936690B (zh) | 2005-10-25 | 2016-06-08 | 盐野义制药株式会社 | 氨基二氢噻嗪衍生物 |
EP2151435A4 (en) | 2007-04-24 | 2011-09-14 | Shionogi & Co | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ALZHEIMER'S DISEASE |
MX2009011498A (es) | 2007-04-24 | 2009-11-10 | Shionogi & Co | Derivados de aminodihidrotiazina sustituida con un grupo ciclico. |
KR20130018370A (ko) | 2008-06-13 | 2013-02-20 | 시오노기세야쿠 가부시키가이샤 | β 세크레타제 저해 작용을 갖는 황 함유 복소환 유도체 |
JPWO2010047372A1 (ja) | 2008-10-22 | 2012-03-22 | 塩野義製薬株式会社 | Bace1阻害活性を有する2−アミノピリミジン−4−オンおよび2−アミノピリジン誘導体 |
UY32799A (es) | 2009-07-24 | 2011-02-28 | Novartis Ag | Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos |
DK2987487T3 (da) | 2009-08-10 | 2020-12-07 | Samumed Llc | Indazolinhibitorer af wnt-signalvejen og terapeutiske anvendelser deraf |
EP2485920B1 (en) | 2009-10-08 | 2016-04-27 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
US8563543B2 (en) | 2009-10-08 | 2013-10-22 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
WO2011071135A1 (ja) | 2009-12-11 | 2011-06-16 | 塩野義製薬株式会社 | オキサジン誘導体 |
DK3001903T3 (en) | 2009-12-21 | 2017-12-18 | Samumed Llc | 1H-PYRAZOLO [3,4 -?] PYRIDINES AND THERAPEUTIC APPLICATIONS THEREOF |
EP2634188A4 (en) | 2010-10-29 | 2014-05-07 | Shionogi & Co | FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE |
US8927721B2 (en) | 2010-10-29 | 2015-01-06 | Shionogi & Co., Ltd. | Naphthyridine derivative |
CA2824220C (en) | 2011-01-13 | 2020-09-01 | Novartis Ag | Novel heterocyclic derivatives and their use in the treatment of neurological disorders |
US20140128385A1 (en) * | 2011-01-13 | 2014-05-08 | Novartis Ag | Bace-2 inhibitors for the treatment of metabolic disorders |
WO2012147763A1 (ja) | 2011-04-26 | 2012-11-01 | 塩野義製薬株式会社 | オキサジン誘導体およびそれを含有するbace1阻害剤 |
AU2012308570B2 (en) | 2011-09-14 | 2016-11-10 | Samumed, Llc | Indazole-3-carboxamides and their use as Wnt/b-catenin signaling pathway inhibitors |
AU2012322329A1 (en) | 2011-10-13 | 2014-05-01 | Novartis Ag | Novel oxazine derivatives and their use in the treatment of disease |
PH12017500997A1 (en) | 2012-04-04 | 2018-02-19 | Samumed Llc | Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof |
WO2013161929A1 (ja) * | 2012-04-26 | 2013-10-31 | 塩野義製薬株式会社 | ピリジニルモルホリノン誘導体およびそれらを含有する医薬組成物 |
DK2770994T3 (da) | 2012-05-04 | 2019-11-11 | Samumed Llc | 1h-pyrazolo[3,4-b]pyridiner og terapeutiske anvendelser deraf |
WO2014065434A1 (en) | 2012-10-24 | 2014-05-01 | Shionogi & Co., Ltd. | Dihydrooxazine or oxazepine derivatives having bace1 inhibitory activity |
CN105120862A (zh) | 2013-01-08 | 2015-12-02 | 萨穆梅德有限公司 | Wnt信号途径的3-(苯并咪唑-2-基)-吲唑抑制剂及其治疗应用 |
WO2014134341A1 (en) | 2013-03-01 | 2014-09-04 | Amgen Inc. | Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
WO2014166906A1 (en) | 2013-04-11 | 2014-10-16 | F. Hoffmann-La Roche Ag | Bace1 inhibitors |
UA117695C2 (uk) * | 2014-02-19 | 2018-09-10 | Х. Луннбек А/С | 2-аміно-3,5,5-трифтор-3,4,5,6-тетрагідропіридини як інгібітори bace1 для лікування хвороби альцгеймера |
WO2016040193A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
WO2016040190A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
WO2016040180A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-benzo[d]imidazol-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040185A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-3h-imidazo[4,5-b]pyridine and therapeutic uses thereof |
WO2016040181A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040188A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040182A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-1h-imidazo[4,5-c]pyridine and therapeutic uses thereof |
WO2016040184A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
CR20170187A (es) | 2014-11-10 | 2018-02-01 | H Lundbeck As | 2-Amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de BACE1 para el tratamiento de la enfermedad de Alzheimer |
MA40941A (fr) | 2014-11-10 | 2017-09-19 | H Lundbeck As | 2-amino-5,5-difluoro-6-(fluorométhyl)-6-phényl-3,4,5,6-tétrahydropyridines comme inhibiteurs de bace1 |
JO3458B1 (ar) | 2014-11-10 | 2020-07-05 | H Lundbeck As | 2- أمينو-6- (دايفلوروميثيل) – 5، 5- ديفلورو-6-فينيل-3،4، 5، 6-تيتراهيدروبيريدين كمثبطات bace1 |
US10226448B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-yl)-1H-pyrazolo[3,4-B]pyridines and therapeutic uses thereof |
US10206908B2 (en) | 2015-08-03 | 2019-02-19 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
WO2017023980A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof |
US10604512B2 (en) | 2015-08-03 | 2020-03-31 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-indazoles and therapeutic uses thereof |
WO2017024026A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-indol-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof |
US10226453B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
WO2017024015A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10231956B2 (en) | 2015-08-03 | 2019-03-19 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1 H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
WO2017023972A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10188634B2 (en) | 2015-08-03 | 2019-01-29 | Samumed, Llc | 3-(3H-imidazo[4,5-C]pyridin-2-yl)-1 H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
US10463651B2 (en) | 2015-08-03 | 2019-11-05 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1H-indazoles and therapeutic uses thereof |
WO2017024004A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10285983B2 (en) | 2015-08-03 | 2019-05-14 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[3,4-B] pyridines and therapeutic uses thereof |
US10392383B2 (en) | 2015-08-03 | 2019-08-27 | Samumed, Llc | 3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10383861B2 (en) | 2015-08-03 | 2019-08-20 | Sammumed, LLC | 3-(1H-pyrrolo[2,3-C]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
US10519169B2 (en) | 2015-08-03 | 2019-12-31 | Samumed, Llc | 3-(1H-pyrrolo[2,3-C]pyridin-2-yl)-1 H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
WO2017024021A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
TW201717948A (zh) | 2015-08-10 | 2017-06-01 | H 朗德貝克公司 | 包括給予2-胺基-3,5,5-三氟-3,4,5,6-四氫吡啶的聯合治療 |
EP3334720A1 (en) | 2015-08-12 | 2018-06-20 | H. Lundbeck A/S | 2-amino-3-fluoro-3-(fluoromethyl)-6-methyl-6-phenyl-3,4,5,6-tetrahydropyridins as bace1 inhibitors |
JP2018531924A (ja) | 2015-09-24 | 2018-11-01 | ファイザー・インク | テトラヒドロピラノ[3,4−d][1,3]オキサジン誘導体、およびbace阻害剤としてのその使用 |
CA3004297A1 (en) | 2015-11-06 | 2017-05-11 | Samumed, Llc | 2-(1h-indazol-3-yl)-3h-imidazo[4,5-c]pyridines and their anti-inflammatory uses thereof |
CN108699051B (zh) | 2016-03-01 | 2021-12-24 | 豪夫迈·罗氏有限公司 | Bace1抑制剂 |
PL3464285T3 (pl) | 2016-06-01 | 2023-02-06 | Biosplice Therapeutics, Inc. | Sposób wytwarzania n-(5-(3-(7-(3-fluorofenylo)-3h-imidazo[4,5-c]pirydyn-2-ylo)-1h-indazol-5-ilo)pirydyn-3-ylo)-3-metylobutanoamidu |
US11834444B2 (en) | 2016-07-07 | 2023-12-05 | Cyclerion Therapeutics, Inc. | Processes for preparation of soluble guanylate cyclase stimulators |
JOP20190003A1 (ar) * | 2016-07-19 | 2019-01-10 | Novartis Ag | مشتق أوكسازين للاستخدام في الوقاية من مرض ألزهايمر في مرضى عُرضه للخطر |
JOP20190081A1 (ar) * | 2016-10-13 | 2019-04-11 | Novartis Ag | مشتق أوكسازين للاستخدام في علاج أو الوقاية من اعتلال وعائي دماغي نشواني |
JP2019535672A (ja) | 2016-10-21 | 2019-12-12 | サミュメッド リミテッド ライアビリティ カンパニー | インダゾール−3−カルボキサミドの使用方法およびwnt/β−カテニンシグナル伝達経路阻害剤としてのそれらの使用 |
MA46696A (fr) | 2016-11-07 | 2019-09-11 | Samumed Llc | Formulations injectables à dose unique prêtes à l'emploi |
MX2019007103A (es) | 2016-12-15 | 2019-11-05 | Amgen Inc | Derivados de tiazina condensados con ciclopropilo como inhibidores de beta-secretasa y metodos de uso. |
MX2019007104A (es) | 2016-12-15 | 2019-11-05 | Amgen Inc | Derivados de dioxido de 1,4-tiazina y dioxido de 1,2,4-tiadiazina como inhibidores de beta-secretasa y metodos de uso. |
CA3047285A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Bicyclic thiazine and oxazine derivatives as beta-secretase inhibitors and methods of use |
CA3047288A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Thiazine derivatives as beta-secretase inhibitors and methods of use |
AU2017376441B2 (en) | 2016-12-15 | 2021-10-14 | Amgen Inc. | Oxazine derivatives as beta-secretase inhibitors and methods of use |
JOP20190178A1 (ar) * | 2017-01-20 | 2019-07-16 | Novartis Ag | تركيبة صيدلانية تتضمن مشتق أوكسازين واستخدامها في علاج أو الوقاية من مرض الزهايمر |
WO2019142111A1 (en) | 2018-01-18 | 2019-07-25 | Novartis Ag | Salt forms of an oxazine derivative bace inhibitor |
CN108997202A (zh) * | 2018-07-10 | 2018-12-14 | 湖南华腾制药有限公司 | 一种(5-三氟甲基-吡啶-2-基)-乙酸盐的制备方法 |
Family Cites Families (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL6911868A (hr) | 1968-08-31 | 1970-03-03 | ||
IL112778A0 (en) | 1994-03-04 | 1995-05-26 | Merck & Co Inc | Substituted heterocycles, their preparation and pharmaceutical compositions containing them |
DE19725802A1 (de) | 1996-07-10 | 1998-01-15 | Lonza Ag | Verfahren zur Herstellung von (S)- oder (R)-3,3,3-trifluor-2-hydroxy-2-methylpropionsäure |
GB9900416D0 (en) * | 1999-01-08 | 1999-02-24 | Alizyme Therapeutics Ltd | Inhibitors |
TW200303742A (en) | 2001-11-21 | 2003-09-16 | Novartis Ag | Organic compounds |
JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
AR043633A1 (es) | 2003-03-20 | 2005-08-03 | Schering Corp | Ligandos de receptores de canabinoides |
CA2525764C (en) | 2003-05-20 | 2012-07-17 | Novartis Ag | N-acyl nitrogen heterocycles as ligands of peroxisome proliferator-activated receptors |
JP2007524682A (ja) | 2004-02-12 | 2007-08-30 | メルク エンド カムパニー インコーポレーテッド | 代謝調節型グルタミン酸受容体−5の調節物質としてのビピリジルアミド |
PE20060692A1 (es) | 2004-09-21 | 2006-07-19 | Lilly Co Eli | Inhibidores bace |
US7888374B2 (en) | 2005-01-28 | 2011-02-15 | Abbott Laboratories | Inhibitors of c-jun N-terminal kinases |
TW200730523A (en) * | 2005-07-29 | 2007-08-16 | Wyeth Corp | Cycloalkyl amino-hydantoin compounds and use thereof for β-secretase modulation |
CN103936690B (zh) * | 2005-10-25 | 2016-06-08 | 盐野义制药株式会社 | 氨基二氢噻嗪衍生物 |
BRPI0808523A2 (pt) | 2007-03-01 | 2014-08-19 | Novartis Vaccines & Diagnostic | Inibidores de pim cinase e métodos de seu uso |
EP2151435A4 (en) | 2007-04-24 | 2011-09-14 | Shionogi & Co | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ALZHEIMER'S DISEASE |
MX2009011498A (es) | 2007-04-24 | 2009-11-10 | Shionogi & Co | Derivados de aminodihidrotiazina sustituida con un grupo ciclico. |
GB0713686D0 (en) | 2007-07-13 | 2007-08-22 | Addex Pharmaceuticals Sa | New compounds 2 |
RU2476431C2 (ru) | 2008-01-18 | 2013-02-27 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Конденсированное производное аминодигидротиазина |
BRPI0907563A2 (pt) * | 2008-02-18 | 2015-08-04 | Hoffmann La Roche | Derivados de 4,5-di-hidro-xazol-2-il amina |
US20100197688A1 (en) | 2008-05-29 | 2010-08-05 | Nantermet Philippe G | Epha4 rtk inhibitors for treatment of neurological and neurodegenerative disorders and cancer |
KR20130018370A (ko) | 2008-06-13 | 2013-02-20 | 시오노기세야쿠 가부시키가이샤 | β 세크레타제 저해 작용을 갖는 황 함유 복소환 유도체 |
TW201028381A (en) | 2008-07-14 | 2010-08-01 | Shionogi & Co | Pyridine derivative having ttk inhibition activity |
JPWO2010047372A1 (ja) | 2008-10-22 | 2012-03-22 | 塩野義製薬株式会社 | Bace1阻害活性を有する2−アミノピリミジン−4−オンおよび2−アミノピリジン誘導体 |
WO2010063718A1 (en) | 2008-12-02 | 2010-06-10 | ETH Zürich | Screening assay for metabolic disease therapeuticals |
US9237972B2 (en) | 2008-12-16 | 2016-01-19 | Kimberly-Clark Worldwide, Inc. | Liquid surfactant compositions that adhere to surfaces and solidify and swell in the presence of water and articles using the same |
US8461160B2 (en) | 2009-05-08 | 2013-06-11 | Hoffmann-La Roche, Inc. | Dihydropyrimidinones |
JP2012180281A (ja) * | 2009-06-29 | 2012-09-20 | Dainippon Sumitomo Pharma Co Ltd | 新規オキサジアゾール誘導体 |
UY32799A (es) | 2009-07-24 | 2011-02-28 | Novartis Ag | Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos |
US8188079B2 (en) * | 2009-08-19 | 2012-05-29 | Hoffman-La Roche Inc. | 3-amino-5-phenyl-5,6-dihydro-2H-[1,4]oxazines |
US20120238557A1 (en) | 2009-11-13 | 2012-09-20 | Shionogi & Co., Ltd. | Aminothiazine or aminooxazine derivative having amino linker |
US7964594B1 (en) | 2009-12-10 | 2011-06-21 | Hoffmann-La Roche Inc. | Amino oxazine derivatives |
WO2011071135A1 (ja) | 2009-12-11 | 2011-06-16 | 塩野義製薬株式会社 | オキサジン誘導体 |
UA103272C2 (uk) | 2009-12-11 | 2013-09-25 | Ф. Хоффманн-Ля Рош Аг | 2-аміно-5,5-дифтор-5,6-дигідро-4h-оксазини як інгібітори bace1 і/або bace2 |
EP2518059A4 (en) | 2009-12-24 | 2013-05-29 | Shionogi & Co | 4-AMINO-1,3-THIAZINE OR OXAZINE DERIVATIVE |
PE20121640A1 (es) | 2009-12-31 | 2012-12-17 | Novartis Ag | Derivados de pirazina como inhibidores de bace |
US8673894B2 (en) | 2010-05-07 | 2014-03-18 | Hoffmann-La Roche Inc. | 2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine or 2,3,6,7-tetrahydro-[1,4]oxazepin-5-ylamine compounds |
BR112012031337A2 (pt) | 2010-06-09 | 2016-10-25 | Janssen Pharmaceutica Nv | derivados de 5-amino-3,6-di-hidro-1h-pirazin-2-ona úteis como inibidores de beta-secretase (bace) |
KR101730937B1 (ko) * | 2010-06-09 | 2017-04-27 | 얀센 파마슈티카 엔.브이. | 베타-세크레타아제(bace) 저해제로 유용한 5,6-디하이드로-2h-[1,4]옥사진-3-일-아민 유도체 |
WO2012006953A1 (en) | 2010-07-13 | 2012-01-19 | Novartis Ag | Oxazine derivatives and their use in the treatment of neurological disorders |
US8524897B2 (en) | 2011-01-12 | 2013-09-03 | Novartis Ag | Crystalline oxazine derivative |
CN103429589A (zh) | 2011-01-12 | 2013-12-04 | 诺瓦提斯公司 | 噁嗪衍生物及其在治疗神经障碍中的用途 |
US20140128385A1 (en) | 2011-01-13 | 2014-05-08 | Novartis Ag | Bace-2 inhibitors for the treatment of metabolic disorders |
CA2824220C (en) * | 2011-01-13 | 2020-09-01 | Novartis Ag | Novel heterocyclic derivatives and their use in the treatment of neurological disorders |
US9169260B2 (en) | 2011-03-22 | 2015-10-27 | Merck Sharp & Dohme Corp. | Amidopyrazole inhibitors of interleukin receptor-associated kinases |
UY34278A (es) | 2011-08-25 | 2013-04-05 | Novartis Ag | Derivados novedosos de oxazina y su uso en el tratamiento de enfermedades |
AU2012322329A1 (en) | 2011-10-13 | 2014-05-01 | Novartis Ag | Novel oxazine derivatives and their use in the treatment of disease |
US8338413B1 (en) | 2012-03-07 | 2012-12-25 | Novartis Ag | Oxazine derivatives and their use in the treatment of neurological disorders |
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