RU2016133626A - 2-амино-3,5,5-трифтор-3,4,5,6-тетрагидропиридины в качестве ингибиторов bace1 для лечения болезни альцгеймера - Google Patents
2-амино-3,5,5-трифтор-3,4,5,6-тетрагидропиридины в качестве ингибиторов bace1 для лечения болезни альцгеймера Download PDFInfo
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- RU2016133626A RU2016133626A RU2016133626A RU2016133626A RU2016133626A RU 2016133626 A RU2016133626 A RU 2016133626A RU 2016133626 A RU2016133626 A RU 2016133626A RU 2016133626 A RU2016133626 A RU 2016133626A RU 2016133626 A RU2016133626 A RU 2016133626A
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- RU
- Russia
- Prior art keywords
- amino
- dimethyl
- tetrahydropyridin
- trifluoro
- fluorophenyl
- Prior art date
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- 208000024827 Alzheimer disease Diseases 0.000 title claims 4
- 229940125759 BACE1 protease inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 21
- -1 3 - ((2R, 5S) -6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl) -4-fluorophenyl Chemical group 0.000 claims 14
- OKTQKJMRIBXJQN-ZWKOTPCHSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-fluoropyridine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1)F)=O)(F)F)(C)F OKTQKJMRIBXJQN-ZWKOTPCHSA-N 0.000 claims 4
- HFGDZWAAFQJTRL-ZWKOTPCHSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methoxypyrazine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NC=C(N=C1)OC)(F)F)(C)F HFGDZWAAFQJTRL-ZWKOTPCHSA-N 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- OKTQKJMRIBXJQN-QZTJIDSGSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-fluoropyridine-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1)F)=O)(F)F)(C)F OKTQKJMRIBXJQN-QZTJIDSGSA-N 0.000 claims 2
- NHAKNDZGVHHIEX-DLBZAZTESA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-1-(difluoromethyl)pyrazole-3-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NN(C=C1)C(F)F)(F)F)(C)F NHAKNDZGVHHIEX-DLBZAZTESA-N 0.000 claims 2
- UFLNEUNQYILWEH-DLBZAZTESA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-2-methyl-1,3-oxazole-4-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1N=C(OC1)C)(F)F)(C)F UFLNEUNQYILWEH-DLBZAZTESA-N 0.000 claims 2
- OTPYSIDSJNTMOG-ZWKOTPCHSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1)Cl)=O)(F)F)(C)F OTPYSIDSJNTMOG-ZWKOTPCHSA-N 0.000 claims 2
- YQEYIBBJTJIMBM-VQTJNVASSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1C)C#N)=O)(F)F)(C)F YQEYIBBJTJIMBM-VQTJNVASSA-N 0.000 claims 2
- VCVSZIBVXNPLJH-RBUKOAKNSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1)C#N)=O)(F)F)(C)F VCVSZIBVXNPLJH-RBUKOAKNSA-N 0.000 claims 2
- YWLRPFXPTFLZDK-RBUKOAKNSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methoxypyridine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1)OC)=O)(F)F)(C)F YWLRPFXPTFLZDK-RBUKOAKNSA-N 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical group 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- PZMYIHWMYVSDEE-HZPDHXFCSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-1,3-thiazole-2-carboxamide Chemical compound S1C(=NC=C1)C(=O)NC1=CC(=C(C=C1)F)[C@]1(N=C([C@](CC1(F)F)(C)F)N)C PZMYIHWMYVSDEE-HZPDHXFCSA-N 0.000 claims 1
- BXYUHPWNQCGGDU-QZTJIDSGSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-1,4-dimethylimidazole-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1N(C=C(N1)C)C)(F)F)(C)F BXYUHPWNQCGGDU-QZTJIDSGSA-N 0.000 claims 1
- NHAKNDZGVHHIEX-IAGOWNOFSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-1-(difluoromethyl)pyrazole-3-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NN(C=C1)C(F)F)(F)F)(C)F NHAKNDZGVHHIEX-IAGOWNOFSA-N 0.000 claims 1
- RRZWWULQZFQDCP-IAGOWNOFSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-1-methylpyrazole-3-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NN(C=C1)C)(F)F)(C)F RRZWWULQZFQDCP-IAGOWNOFSA-N 0.000 claims 1
- UFLNEUNQYILWEH-IAGOWNOFSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-2-methyl-1,3-oxazole-4-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1N=C(OC1)C)(F)F)(C)F UFLNEUNQYILWEH-IAGOWNOFSA-N 0.000 claims 1
- VBCSAZLAPMXFSR-IAGOWNOFSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-2-methyl-1,3-oxazole-5-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=CN=C(O1)C)(F)F)(C)F VBCSAZLAPMXFSR-IAGOWNOFSA-N 0.000 claims 1
- CHSNPRBZZZJYHX-IAGOWNOFSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-3-methyl-1,2-oxazole-5-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=CC(=NO1)C)(F)F)(C)F CHSNPRBZZZJYHX-IAGOWNOFSA-N 0.000 claims 1
- HOESHHMMCCAKCR-IAGOWNOFSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-4-bromo-1-methylimidazole-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1N(C=C(N1)Br)C)(F)F)(C)F HOESHHMMCCAKCR-IAGOWNOFSA-N 0.000 claims 1
- MGSJYJDBSCSZJE-RTBURBONSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-4-chlorobenzamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=CC=C(C=C1)Cl)=O)(F)F)(C)F MGSJYJDBSCSZJE-RTBURBONSA-N 0.000 claims 1
- JOQPMLZUFXKUND-IAGOWNOFSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-4-methyl-1,3-thiazole-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1SC=C(N1)C)(F)F)(C)F JOQPMLZUFXKUND-IAGOWNOFSA-N 0.000 claims 1
- OTPYSIDSJNTMOG-QZTJIDSGSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1)Cl)=O)(F)F)(C)F OTPYSIDSJNTMOG-QZTJIDSGSA-N 0.000 claims 1
- VCVSZIBVXNPLJH-RTBURBONSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1)C#N)=O)(F)F)(C)F VCVSZIBVXNPLJH-RTBURBONSA-N 0.000 claims 1
- HFGDZWAAFQJTRL-QZTJIDSGSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methoxypyrazine-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NC=C(N=C1)OC)(F)F)(C)F HFGDZWAAFQJTRL-QZTJIDSGSA-N 0.000 claims 1
- RFYVGRKMWIRDAM-QZTJIDSGSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methoxypyrimidine-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NC=C(C=N1)OC)(F)F)(C)F RFYVGRKMWIRDAM-QZTJIDSGSA-N 0.000 claims 1
- WMKOPKSKWBVFKU-HZPDHXFCSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methyl-1,2,4-oxadiazole-3-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NOC(=N1)C)(F)F)(C)F WMKOPKSKWBVFKU-HZPDHXFCSA-N 0.000 claims 1
- UMBJREUTONPUSK-QZTJIDSGSA-N N-[3-[(2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methylfuran-2-carboxamide Chemical compound NC=1[C@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1OC(=CC1)C)(F)F)(C)F UMBJREUTONPUSK-QZTJIDSGSA-N 0.000 claims 1
- PZMYIHWMYVSDEE-JKSUJKDBSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-1,3-thiazole-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1SC=CN1)(F)F)(C)F PZMYIHWMYVSDEE-JKSUJKDBSA-N 0.000 claims 1
- ZADSHEURMUBVAC-JKSUJKDBSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-1-methyl-1,2,4-triazole-3-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NN(C=N1)C)(F)F)(C)F ZADSHEURMUBVAC-JKSUJKDBSA-N 0.000 claims 1
- ANSIAVPOQGVLFC-ZWKOTPCHSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-2,5-dimethyl-1,3-oxazole-4-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1N=C(OC1C)C)(F)F)(C)F ANSIAVPOQGVLFC-ZWKOTPCHSA-N 0.000 claims 1
- KGWKKESEYVBROW-RBUKOAKNSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-3-fluoro-5-methoxypyridine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1F)OC)=O)(F)F)(C)F KGWKKESEYVBROW-RBUKOAKNSA-N 0.000 claims 1
- SUTNBTCNHDOKDD-JKSUJKDBSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-3-methyl-1,2,4-oxadiazole-5-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NC(=NO1)C)(F)F)(C)F SUTNBTCNHDOKDD-JKSUJKDBSA-N 0.000 claims 1
- HOESHHMMCCAKCR-DLBZAZTESA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-4-bromo-1-methylimidazole-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1N(C=C(N1)Br)C)(F)F)(C)F HOESHHMMCCAKCR-DLBZAZTESA-N 0.000 claims 1
- JOQPMLZUFXKUND-DLBZAZTESA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-4-methyl-1,3-thiazole-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1SC=C(N1)C)(F)F)(C)F JOQPMLZUFXKUND-DLBZAZTESA-N 0.000 claims 1
- JZWNILHOEJVHHZ-RBUKOAKNSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-fluoro-3-methylpyridine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(C1=NC=C(C=C1C)F)=O)(F)F)(C)F JZWNILHOEJVHHZ-RBUKOAKNSA-N 0.000 claims 1
- QIJVGCAOVFBXFY-RBUKOAKNSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methoxy-3-methylpyrazine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NC=C(N=C1C)OC)(F)F)(C)F QIJVGCAOVFBXFY-RBUKOAKNSA-N 0.000 claims 1
- RFYVGRKMWIRDAM-ZWKOTPCHSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methoxypyrimidine-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C1=NC=C(C=N1)OC)(F)F)(C)F RFYVGRKMWIRDAM-ZWKOTPCHSA-N 0.000 claims 1
- ZXEUQJAXUTWMOI-JKSUJKDBSA-N N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-methyl-1,3,4-oxadiazole-2-carboxamide Chemical compound NC=1[C@@](CC([C@@](N1)(C)C=1C=C(C=CC1F)NC(=O)C=1OC(=NN1)C)(F)F)(C)F ZXEUQJAXUTWMOI-JKSUJKDBSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 125000001786 isothiazolyl group Chemical group 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000003373 pyrazinyl group Chemical group 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/435—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
-
- 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
- A61K31/435—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
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D227/00—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00
- C07D227/02—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D227/06—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D227/10—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D413/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
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| DKPA201400086 | 2014-02-19 | ||
| DKPA201400086 | 2014-02-19 | ||
| DKPA201400349 | 2014-07-01 | ||
| DKPA201400349 | 2014-07-01 | ||
| PCT/EP2015/053327 WO2015124576A1 (en) | 2014-02-19 | 2015-02-17 | 2-amino-3, 5, 5-trifluoro-3, 4, 5, 6-tetrahydropyridines as bace1 inhibitors for treatment of alzheimer's disease |
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| PE20161225A1 (es) | 2014-02-19 | 2016-12-04 | H Lundbeck As | 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas como inhibidores de bace1 para el tratamiento de la enfermedad de alzheimer |
| 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 |
| 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 |
| 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 |
| JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| 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 |
| WO2017025559A1 (en) * | 2015-08-12 | 2017-02-16 | H. Lundbeck A/S | 2-amino-3-fluoro-3-(fluoromethyl)-6-methyl-6-phenyl-3,4,5,6-tetrahydropyridins as bace1 inhibitors |
| EP3347486A4 (en) * | 2015-09-09 | 2019-06-19 | The Trustees of Columbia University in the City of New York | REDUCTION OF ER-MAM-LOCALIZED APP-C99 AND METHOD FOR THE TREATMENT OF ALZHEIMER DISEASE |
| TW201726651A (zh) * | 2015-09-23 | 2017-08-01 | 健生藥品公司 | ２，３，４，５－四氫吡啶－６－胺衍生物 |
| US10034861B2 (en) | 2016-07-04 | 2018-07-31 | H. Lundbeck A/S | 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors |
| JP2020500841A (ja) | 2016-10-28 | 2020-01-16 | ハー・ルンドベック・アクチエゼルスカベット | イミダゾピラジノンの投与を含む併用療法 |
| EP3532064B1 (en) | 2016-10-28 | 2020-07-29 | H. Lundbeck A/S | Combination treatments comprising imidazopyrazinones for the treatment of psychiatric and/or cognitive disorders |
| TW201829394A (zh) | 2016-12-21 | 2018-08-16 | 丹麥商Ｈ 朗德貝克公司 | 作為ｂａｃｅ１抑制劑之６-胺基-５-氟-５-（氟甲基）-２，３，４，５-四氫吡啶-２-基-苯基-５-（甲氧基-ｄ）-吡-２-甲醯胺及其氟化衍生物 |
| CN111601593B (zh) | 2017-10-05 | 2022-04-15 | 弗尔康医疗公司 | P38激酶抑制剂降低dux4和下游基因表达以用于治疗fshd |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| AR113926A1 (es) | 2017-12-14 | 2020-07-01 | H Lundbeck As | Derivados de 1h-pirazolo[4,3-b]piridinas |
| CN111465410B (zh) | 2017-12-14 | 2022-10-25 | H.隆德贝克有限公司 | 包括施用1h-吡唑并[4,3-b]吡啶的组合治疗 |
| EP3728250A1 (en) | 2017-12-20 | 2020-10-28 | H. Lundbeck A/S | PYRAZOLO[3,4-beta]PYRIDINES AND IMIDAZO[1,5-beta]PYRIDAZINES AS PDE1 INHIBITORS |
| KR102507861B1 (ko) | 2018-04-19 | 2023-03-09 | 삼성에스디에스 주식회사 | 부채널 공격에 안전한 연산 장치 및 방법 |
| KR102510077B1 (ko) | 2018-04-24 | 2023-03-14 | 삼성에스디에스 주식회사 | 부채널 공격에 안전한 연산 장치 및 방법 |
| US12042492B2 (en) | 2020-10-09 | 2024-07-23 | Texas Tech University System | BACE1 inhibitory ligand molecules against amyloid beta-induced synaptic and mitochondrial toxicities |
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| EP1395257A1 (en) * | 2001-06-12 | 2004-03-10 | Elan Pharmaceuticals, Inc. | Macrocycles useful in the treatment of alzheimer's disease |
| GB0124928D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| WO2003068747A1 (en) * | 2002-02-12 | 2003-08-21 | Smithkline Beecham Corporation | Nicotinamide derivates useful as p38 inhibitors |
| TWI431004B (zh) * | 2008-05-02 | 2014-03-21 | Lilly Co Eli | Ｂａｃｅ抑制劑 |
| WO2011154431A1 (en) * | 2010-06-09 | 2011-12-15 | Janssen Pharmaceutica Nv | 5,6-dihydro-2h-[1,4]oxazin-3-yl-amine derivatives useful as inhibitors of beta-secretase (bace) |
| WO2012057248A1 (ja) * | 2010-10-29 | 2012-05-03 | 塩野義製薬株式会社 | ナフチリジン誘導体 |
| US20130281449A1 (en) | 2011-01-12 | 2013-10-24 | Novartis Ag | Oxazine Derivatives and their Use in the Treatment of Neurological Disorders |
| PL2663561T3 (pl) | 2011-01-13 | 2016-10-31 | Nowe pochodne heterocykliczne i ich zastosowanie w leczeniu zaburzeń neurologicznych | |
| US8754075B2 (en) | 2011-04-11 | 2014-06-17 | Hoffmann-La Roche Inc. | 1,3-oxazines as BACE1 and/or BACE2 inhibitors |
| JPWO2012147763A1 (ja) * | 2011-04-26 | 2014-07-28 | 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 |
| BR112013031098A2 (pt) * | 2011-06-07 | 2016-12-06 | Hoffmann La Roche | halogeno-alquil-1,3 oxazinas como inibidores de bace1 e/ou bace2 |
| UY34278A (es) * | 2011-08-25 | 2013-04-05 | Novartis Ag | Derivados novedosos de oxazina y su uso en el tratamiento de enfermedades |
| US8338413B1 (en) * | 2012-03-07 | 2012-12-25 | Novartis Ag | Oxazine derivatives and their use in the treatment of neurological disorders |
| US9493485B2 (en) | 2012-03-20 | 2016-11-15 | Imago Pharmaceuticals, Inc. | Spirocyclic dihydro-thiazine and dihydro-oxazine BACE inhibitors, and compositions and uses thereof |
| WO2014056816A1 (en) | 2012-10-10 | 2014-04-17 | F. Hoffmann-La Roche Ag | COMBINATION OF AN Aβ ANTIBODY AND A BACE INHIBITOR |
| US9540359B2 (en) | 2012-10-24 | 2017-01-10 | Shionogi & Co., Ltd. | Dihydrooxazine or oxazepine derivatives having BACE1 inhibitory activity |
| TW201446758A (zh) | 2013-03-01 | 2014-12-16 | Amgen Inc | 作爲β－分泌酶抑制劑的全氟化５，６－二氫－４Ｈ－１，３－□－２－胺化合物及其用途 |
| PE20161225A1 (es) | 2014-02-19 | 2016-12-04 | H Lundbeck As | 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas como inhibidores de bace1 para el tratamiento de la enfermedad de alzheimer |
| TW201623295A (zh) | 2014-04-11 | 2016-07-01 | 塩野義製藥股份有限公司 | 具有ｂａｃｅ１抑制活性之二氫噻及二氫衍生物 |
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| UA117695C2 (uk) | 2018-09-10 |
| ECSP16072941A (es) | 2017-02-24 |
| DOP2016000194A (es) | 2016-09-30 |
| EA031132B1 (ru) | 2018-11-30 |
| AP2016009370A0 (en) | 2016-08-31 |
| SG11201606812WA (en) | 2016-09-29 |
| KR20160115936A (ko) | 2016-10-06 |
| AU2015220873A1 (en) | 2016-08-11 |
| MA39225A1 (fr) | 2017-04-28 |
| EA201691447A1 (ru) | 2016-12-30 |
| JP2017506237A (ja) | 2017-03-02 |
| AR099489A1 (es) | 2016-07-27 |
| PE20161225A1 (es) | 2016-12-04 |
| PH12016501600A1 (en) | 2017-02-06 |
| TW201609700A (zh) | 2016-03-16 |
| CN106029639B (zh) | 2019-01-08 |
| CN106029639A (zh) | 2016-10-12 |
| JP6483146B2 (ja) | 2019-03-13 |
| CA2940028A1 (en) | 2015-08-27 |
| IL246875A0 (en) | 2016-08-31 |
| CL2016002072A1 (es) | 2017-01-20 |
| EP3107897A1 (en) | 2016-12-28 |
| GEP20186892B (en) | 2018-09-10 |
| US9353084B2 (en) | 2016-05-31 |
| CR20160352A (es) | 2016-10-20 |
| WO2015124576A1 (en) | 2015-08-27 |
| US20150232449A1 (en) | 2015-08-20 |
| US20170066741A1 (en) | 2017-03-09 |
| RU2016133626A3 (enExample) | 2018-09-25 |
| MX2016010777A (es) | 2016-10-26 |
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Legal Events
| Date | Code | Title | Description |
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| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20190111 |