EA031132B1 - 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
- Publication number
- EA031132B1 EA031132B1 EA201691447A EA201691447A EA031132B1 EA 031132 B1 EA031132 B1 EA 031132B1 EA 201691447 A EA201691447 A EA 201691447A EA 201691447 A EA201691447 A EA 201691447A EA 031132 B1 EA031132 B1 EA 031132B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- amino
- fluorophenyl
- trifluoro
- dimethyl
- carboxamide
- Prior art date
Links
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 7
- 238000011282 treatment Methods 0.000 title claims description 9
- BFTKEARFXHXNIW-UHFFFAOYSA-N 3,3,5-trifluoro-4,5-dihydro-2H-pyridin-6-amine Chemical class NC1=NCC(CC1F)(F)F BFTKEARFXHXNIW-UHFFFAOYSA-N 0.000 title 1
- 229940125759 BACE1 protease inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- -1 (fluoromethyl) oxazole-2-carboxamide Chemical compound 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 27
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 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 description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 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 description 2
- 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 description 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 class 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 description 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 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
- 125000004504 1,2,4-oxadiazolyl 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
- QWEWLLNSJDTOKH-UHFFFAOYSA-N 1,3-thiazole-2-carboxamide Chemical compound NC(=O)C1=NC=CS1 QWEWLLNSJDTOKH-UHFFFAOYSA-N 0.000 claims 1
- HQHTWOUEFQKMAQ-UHFFFAOYSA-N 3-chloropyridine-2-carboxamide Chemical class NC(=O)C1=NC=CC=C1Cl HQHTWOUEFQKMAQ-UHFFFAOYSA-N 0.000 claims 1
- HRHNVVBCKXBGOT-UHFFFAOYSA-N 5-methoxypyrazine-2-carboxamide Chemical compound COC1=CN=C(C(N)=O)C=N1 HRHNVVBCKXBGOT-UHFFFAOYSA-N 0.000 claims 1
- SESHLZVBBWETNW-UHFFFAOYSA-N 5-methoxypyrimidine-2-carboxamide Chemical compound COC1=CN=C(C(N)=O)N=C1 SESHLZVBBWETNW-UHFFFAOYSA-N 0.000 claims 1
- REHDBMJDLGLCJG-UHFFFAOYSA-N FC(F)ONC(=O)C1=CC=CC=N1 Chemical compound FC(F)ONC(=O)C1=CC=CC=N1 REHDBMJDLGLCJG-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-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
- 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
- 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
- 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
- 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
- HBWFWRJFTRXCCC-UHFFFAOYSA-N O1C=NC(=C1)C(=O)NC(F)F Chemical compound O1C=NC(=C1)C(=O)NC(F)F HBWFWRJFTRXCCC-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- IYWYWUOIBLBATR-UHFFFAOYSA-N n-(difluoromethyl)pyrazine-2-carboxamide Chemical compound FC(F)NC(=O)C1=CN=CC=N1 IYWYWUOIBLBATR-UHFFFAOYSA-N 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 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
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- 238000000034 method Methods 0.000 description 85
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Classifications
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- 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
- 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
-
- 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
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- 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
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Applications Claiming Priority (3)
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| DKPA201400086 | 2014-02-19 | ||
| 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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| EA201691447A1 EA201691447A1 (ru) | 2016-12-30 |
| EA031132B1 true EA031132B1 (ru) | 2018-11-30 |
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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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| TWI431004B (zh) * | 2008-05-02 | 2014-03-21 | Lilly Co Eli | Ｂａｃｅ抑制劑 |
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| 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 | |
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| 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 |
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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 |
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- 2015-02-17 GE GEAP201514248A patent/GEP20186892B/en unknown
- 2015-02-17 JP JP2016551851A patent/JP6483146B2/ja not_active Expired - Fee Related
- 2015-02-17 CA CA2940028A patent/CA2940028A1/en not_active Abandoned
- 2015-02-17 TW TW104105281A patent/TW201609700A/zh unknown
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- 2015-02-17 SG SG11201606812WA patent/SG11201606812WA/en unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| UA117695C2 (uk) | 2018-09-10 |
| ECSP16072941A (es) | 2017-02-24 |
| DOP2016000194A (es) | 2016-09-30 |
| 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 |
| RU2016133626A (ru) | 2018-03-20 |
| 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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