HUE033376T2 - Camsylate salt of (1r,1'R,4R)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin- 3-yl]-3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine and crystalline forms thereof for the treatment of A[beta]-related pathologies such as e.g. Alzheimer's... - Google Patents
Camsylate salt of (1r,1'R,4R)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin- 3-yl]-3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine and crystalline forms thereof for the treatment of A[beta]-related pathologies such as e.g. Alzheimer's... Download PDFInfo
- Publication number
- HUE033376T2 HUE033376T2 HUE13733415A HUE13733415A HUE033376T2 HU E033376 T2 HUE033376 T2 HU E033376T2 HU E13733415 A HUE13733415 A HU E13733415A HU E13733415 A HUE13733415 A HU E13733415A HU E033376 T2 HUE033376 T2 HU E033376T2
- Authority
- HU
- Hungary
- Prior art keywords
- disease
- alzheimer
- cyclohexane
- methyl
- dementia
- Prior art date
Links
- 208000024827 Alzheimer disease Diseases 0.000 title abstract description 90
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title abstract description 46
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 title abstract description 42
- 150000003839 salts Chemical group 0.000 title abstract description 14
- 238000011282 treatment Methods 0.000 title description 9
- 239000013078 crystal Chemical group 0.000 title description 4
- 230000001575 pathological effect Effects 0.000 title description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 title 1
- -1 prop-l-yn-l-yl Chemical group 0.000 title 1
- 206010019909 Hernia Diseases 0.000 claims 1
- JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 claims 1
- 241000282887 Suidae Species 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 abstract description 46
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 abstract description 37
- 230000007170 pathology Effects 0.000 abstract description 25
- 206010059245 Angiopathy Diseases 0.000 abstract description 18
- 102000013455 Amyloid beta-Peptides Human genes 0.000 abstract description 17
- 108010090849 Amyloid beta-Peptides Proteins 0.000 abstract description 17
- 206010044688 Trisomy 21 Diseases 0.000 abstract description 17
- 201000010374 Down Syndrome Diseases 0.000 abstract description 15
- 208000018737 Parkinson disease Diseases 0.000 abstract description 15
- 206010039966 Senile dementia Diseases 0.000 abstract description 15
- 230000007850 degeneration Effects 0.000 abstract description 15
- 238000000034 method Methods 0.000 abstract description 15
- 230000002792 vascular Effects 0.000 abstract description 14
- 206010036631 Presenile dementia Diseases 0.000 abstract description 13
- 230000001054 cortical effect Effects 0.000 abstract description 13
- 230000003412 degenerative effect Effects 0.000 abstract description 13
- 201000002212 progressive supranuclear palsy Diseases 0.000 abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 9
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 description 41
- 239000000203 mixture Substances 0.000 description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- 208000010877 cognitive disease Diseases 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 102100021257 Beta-secretase 1 Human genes 0.000 description 17
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 16
- 239000003814 drug Substances 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 208000024891 symptom Diseases 0.000 description 15
- 201000010099 disease Diseases 0.000 description 14
- 230000004770 neurodegeneration Effects 0.000 description 14
- 208000000044 Amnesia Diseases 0.000 description 13
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 13
- 208000026139 Memory disease Diseases 0.000 description 13
- 230000006984 memory degeneration Effects 0.000 description 13
- 208000023060 memory loss Diseases 0.000 description 13
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 12
- 208000028698 Cognitive impairment Diseases 0.000 description 12
- 241000282414 Homo sapiens Species 0.000 description 12
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
- 230000006735 deficit Effects 0.000 description 12
- 208000027061 mild cognitive impairment Diseases 0.000 description 12
- 238000000634 powder X-ray diffraction Methods 0.000 description 12
- 238000002560 therapeutic procedure Methods 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 10
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 10
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 9
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 9
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 9
- 238000003776 cleavage reaction Methods 0.000 description 9
- 238000004821 distillation Methods 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 230000008021 deposition Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000002050 diffraction method Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- DPXQBNIZPADHOT-UHFFFAOYSA-N 6-bromospiro[3h-indene-2,4'-cyclohexane]-1,1'-dione Chemical compound O=C1C2=CC(Br)=CC=C2CC21CCC(=O)CC2 DPXQBNIZPADHOT-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000003693 atypical antipsychotic agent Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- ORMNRFOQVUFLJE-UHFFFAOYSA-N 6-bromo-4'-methoxyspiro[3h-indene-2,1'-cyclohexane]-1-one Chemical compound C1CC(OC)CCC11C(=O)C2=CC(Br)=CC=C2C1 ORMNRFOQVUFLJE-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 3
- 208000037259 Amyloid Plaque Diseases 0.000 description 3
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 3
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 3
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 230000003943 amyloidogenic processing Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 230000037411 cognitive enhancing Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003797 essential amino acid Substances 0.000 description 3
- 235000020776 essential amino acid Nutrition 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
- 230000006883 memory enhancing effect Effects 0.000 description 3
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 102000036664 ADAM10 Human genes 0.000 description 2
- 108091007504 ADAM10 Proteins 0.000 description 2
- 231100000582 ATP assay Toxicity 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 2
- 229940122601 Esterase inhibitor Drugs 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000007450 amyloidogenic pathway Effects 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
- 238000011254 conventional chemotherapy Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000002329 esterase inhibitor Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229960005017 olanzapine Drugs 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 238000009790 rate-determining step (RDS) Methods 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 2
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 2
- QICKHKWSOJEAII-UHFFFAOYSA-N (5-prop-1-ynylpyridin-3-yl)boronic acid Chemical compound CC#CC1=CN=CC(B(O)O)=C1 QICKHKWSOJEAII-UHFFFAOYSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- LQOCXPOKEPYGTJ-UHFFFAOYSA-N 2-amino-6-[3-(3-methoxyphenyl)phenyl]-3,6-dimethyl-5h-pyrimidin-4-one Chemical compound COC1=CC=CC(C=2C=C(C=CC=2)C2(C)N=C(N)N(C)C(=O)C2)=C1 LQOCXPOKEPYGTJ-UHFFFAOYSA-N 0.000 description 1
- CUDPUYMADCMXBY-UHFFFAOYSA-N 2-oxopropanethioamide Chemical compound CC(=O)C(N)=S CUDPUYMADCMXBY-UHFFFAOYSA-N 0.000 description 1
- JPNPRWMRUCIEMN-UHFFFAOYSA-N 3-ditert-butylphosphaniumylpropane-1-sulfonate Chemical compound CC(C)(C)P(C(C)(C)C)CCCS(O)(=O)=O JPNPRWMRUCIEMN-UHFFFAOYSA-N 0.000 description 1
- SEQHEDQNODAFIU-UHFFFAOYSA-N 6-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2CCC(=O)C2=C1 SEQHEDQNODAFIU-UHFFFAOYSA-N 0.000 description 1
- 208000018282 ACys amyloidosis Diseases 0.000 description 1
- 108091007505 ADAM17 Proteins 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
- 101710150192 Beta-secretase 1 Proteins 0.000 description 1
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 description 1
- 101710115937 Microtubule-associated protein tau Proteins 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 description 1
- 208000001294 Nociceptive Pain Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000006933 amyloid-beta aggregation Effects 0.000 description 1
- 230000003942 amyloidogenic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002205 anti-dementic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 229960004372 aripiprazole Drugs 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- PVYPHUYXKVVURH-UHFFFAOYSA-N boron;2-methylpropan-2-amine Chemical compound [B].CC(C)(C)N PVYPHUYXKVVURH-UHFFFAOYSA-N 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- 229940068796 clozaril Drugs 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000003182 dose-response assay Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 108091007739 gamma-secretases Proteins 0.000 description 1
- 102000038383 gamma-secretases Human genes 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940003380 geodon Drugs 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000004050 mood stabilizer Substances 0.000 description 1
- 229940127237 mood stabilizer Drugs 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229960004431 quetiapine Drugs 0.000 description 1
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
- ZTHJULTYCAQOIJ-WXXKFALUSA-N quetiapine fumarate Chemical compound [H+].[H+].[O-]C(=O)\C=C\C([O-])=O.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 ZTHJULTYCAQOIJ-WXXKFALUSA-N 0.000 description 1
- 229940106887 risperdal Drugs 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940035004 seroquel Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229940034173 symbyax Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- CESUXLKAADQNTB-UHFFFAOYSA-N tert-butanesulfinamide Chemical compound CC(C)(C)S(N)=O CESUXLKAADQNTB-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- YZYKBQUWMPUVEN-UHFFFAOYSA-N zafuleptine Chemical compound OC(=O)CCCCCC(C(C)C)NCC1=CC=C(F)C=C1 YZYKBQUWMPUVEN-UHFFFAOYSA-N 0.000 description 1
- 229960000607 ziprasidone Drugs 0.000 description 1
- 229940039925 zyprexa Drugs 0.000 description 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
-
- 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
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- 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
- C07D401/10—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 carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261662592P | 2012-06-21 | 2012-06-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUE033376T2 true HUE033376T2 (en) | 2017-11-28 |
Family
ID=48746084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HUE13733415A HUE033376T2 (en) | 2012-06-21 | 2013-06-20 | Camsylate salt of (1r,1'R,4R)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin- 3-yl]-3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine and crystalline forms thereof for the treatment of A[beta]-related pathologies such as e.g. Alzheimer's... |
Country Status (42)
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8415483B2 (en) | 2010-12-22 | 2013-04-09 | Astrazeneca Ab | Compounds and their use as BACE inhibitors |
| US9650336B2 (en) | 2011-10-10 | 2017-05-16 | Astrazeneca Ab | Mono-fluoro beta-secretase inhibitors |
| US9000182B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | 2H-imidazol-4-amine compounds and their use as BACE inhibitors |
| US9000183B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cyclohexane-1,2′-indene-1′,2″-imidazol compounds and their use as BACE inhibitors |
| US9000184B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cyclohexane-1,2′-naphthalene-1′,2″-imidazol compounds and their use as BACE inhibitors |
| US9000185B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cycloalkyl ether compounds and their use as BACE inhibitors |
| US10053453B2 (en) | 2014-10-07 | 2018-08-21 | Astrazeneca Ab | Compounds and their use as BACE inhibitors |
| JP6546410B2 (ja) * | 2015-02-23 | 2019-07-17 | ローム株式会社 | 電力供給装置、ａｃアダプタ、ａｃチャージャ、電子機器および電力供給システム |
| AR107893A1 (es) * | 2016-03-15 | 2018-06-28 | Astrazeneca Ab | TERAPIAS COMBINADAS, COMBINACIÓN DE UN INHIBIDOR DE BACE Y UN ANTICUERPO O UN FRAGMENTO DE UNIÓN AL ANTÍGENO PARA EL TRATAMIENTO DE UN TRASTORNO ASOCIADO CON LA ACUMULACIÓN DE b AMILOIDE |
| AR107783A1 (es) * | 2016-03-15 | 2018-06-06 | Lilly Co Eli | Terapia de combinación |
| MX2021011105A (es) * | 2019-03-14 | 2021-10-22 | Astrazeneca Ab | Lanabecestat para la perdida de peso. |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100452491B1 (ko) * | 2001-03-29 | 2004-10-12 | 한미약품 주식회사 | 신규한 결정형 암로디핀 캠실레이트 염 및 그의 제조방법 |
| WO2002098462A1 (en) | 2001-06-01 | 2002-12-12 | Ono Pharmaceutical Co., Ltd. | Remedies containing aldose reductase inhibitor as the active ingredient for demyelinating diseases or diseases associated with demyelination |
| US7592348B2 (en) | 2003-12-15 | 2009-09-22 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| ES2332184T3 (es) | 2004-03-22 | 2010-01-28 | ELI LILLY & COMPANY | Derivados de piridilo y su uso como antagonistas del receptor mglu5. |
| CN101228163A (zh) | 2005-06-14 | 2008-07-23 | 先灵公司 | 天冬氨酰蛋白酶抑制剂 |
| WO2007058601A1 (en) | 2005-11-21 | 2007-05-24 | Astrazeneca Ab | Novel 2-amino-imidazole-4-one compounds and their use in the manufacture of a medicament to be used in the treatment of cognitive impairment, alzheimer’s disease, neurodegeneration and dementia |
| TW200734311A (en) | 2005-11-21 | 2007-09-16 | Astrazeneca Ab | New compounds |
| EP1966163A1 (en) | 2005-12-21 | 2008-09-10 | Boehringer Ingelheim International GmbH | Pyrimidine derivatives useful as inhibitors of pkc-theta |
| WO2007100536A1 (en) | 2006-02-24 | 2007-09-07 | Wyeth | DIHYDROSPIRO[DIBENZO[A,D][7]ANNULENE-5,4'-IMIDAZOL] COMPOUNDS FOR THE INHIBITION OF β-SECRETASE |
| EP2032542A2 (en) | 2006-06-12 | 2009-03-11 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| WO2008076043A1 (en) | 2006-12-20 | 2008-06-26 | Astrazeneca Ab | Novel 2-amino-5,5-diaryl-imidazol-4-ones |
| US20090325993A1 (en) | 2007-02-01 | 2009-12-31 | Nadia Mamoona Ahmad | GLYT1 Transporter Inhibitors and Uses Thereof in Treatment of Neurological and Neuropsychiatric Disorders |
| CA2686589A1 (en) | 2007-05-07 | 2008-11-13 | Schering Corporation | Gamma secretase modulators |
| WO2009100169A1 (en) | 2008-02-06 | 2009-08-13 | Glaxo Group Limited | Dual pharmacophores - pde4-muscarinic antagonistics |
| FR2929943B1 (fr) * | 2008-04-15 | 2010-09-24 | Inst Rech Developpement Ird | Sels de quinoleines 2-substituees |
| CN102105475B (zh) | 2008-07-28 | 2014-04-09 | 卫材R&D管理有限公司 | 螺氨基二氢噻嗪衍生物 |
| WO2010021680A2 (en) | 2008-08-19 | 2010-02-25 | Vitae Pharmaceuticals, Inc. | Inhibitors of beta-secretase |
| CA2736130C (en) | 2008-09-11 | 2014-01-14 | Amgen Inc. | Spiro-tetracyclic ring compounds as beta-secretase modulators and methods of use |
| KR101908255B1 (ko) | 2009-03-13 | 2018-10-15 | 비타이 파마슈티컬즈, 인코포레이티드 | 베타세크리타아제 저해제 |
| TW201105650A (en) | 2009-07-02 | 2011-02-16 | Astrazeneca Ab | New compounds |
| UY32750A (es) | 2009-07-02 | 2011-01-31 | Astrazeneca Ab | Imidazoles sustituidos y uso de los mismos |
| JP5828848B2 (ja) | 2010-02-24 | 2015-12-09 | ヴァイティー ファーマシューティカルズ，インコーポレイテッド | ベータセクレターゼインヒビター |
| AR080865A1 (es) | 2010-03-31 | 2012-05-16 | Array Biopharma Inc | Derivados de espirotetrahidronaftaleno, composiciones farmaceuticas que los contienen, proceso de preparacion y uso de los mismos para tratar enfermedades neurodegenerativas,tal como alzheimer. |
| WO2011130741A1 (en) | 2010-04-16 | 2011-10-20 | Array Biopharma Inc. | Compounds for treating neurodegenerative diseases |
| WO2012019056A1 (en) | 2010-08-05 | 2012-02-09 | Amgen Inc. | Amino-iso-indole, amino-aza-iso-indole, amino-dihydroisoquinoline and amino-benzoxazine compounds as beta-secretase modulators and methods of use |
| AR083169A1 (es) | 2010-09-24 | 2013-02-06 | Array Biopharma Inc | Compuestos para tratar enfermedades neurodegenerativas |
| US20120157448A1 (en) | 2010-11-22 | 2012-06-21 | Adam Cook | Compounds for treating neurodegenerative diseases |
| US8415483B2 (en) | 2010-12-22 | 2013-04-09 | Astrazeneca Ab | Compounds and their use as BACE inhibitors |
| US9650336B2 (en) | 2011-10-10 | 2017-05-16 | Astrazeneca Ab | Mono-fluoro beta-secretase inhibitors |
| US9000185B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cycloalkyl ether compounds and their use as BACE inhibitors |
| US9000184B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cyclohexane-1,2′-naphthalene-1′,2″-imidazol compounds and their use as BACE inhibitors |
| US9000182B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | 2H-imidazol-4-amine compounds and their use as BACE inhibitors |
| US9000183B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cyclohexane-1,2′-indene-1′,2″-imidazol compounds and their use as BACE inhibitors |
-
2013
- 2013-06-13 US US13/916,754 patent/US10548882B2/en active Active
- 2013-06-19 AR ARP130102162 patent/AR091495A1/es unknown
- 2013-06-20 NZ NZ702742A patent/NZ702742A/en not_active IP Right Cessation
- 2013-06-20 HR HRP20170359TT patent/HRP20170359T1/hr unknown
- 2013-06-20 JP JP2015517850A patent/JP2015520221A/ja active Pending
- 2013-06-20 DK DK13733415.7T patent/DK2864316T3/en active
- 2013-06-20 EP EP13733415.7A patent/EP2864316B1/en active Active
- 2013-06-20 WO PCT/GB2013/051606 patent/WO2013190302A1/en not_active Ceased
- 2013-06-20 PT PT137334157T patent/PT2864316T/pt unknown
- 2013-06-20 HU HUE13733415A patent/HUE033376T2/en unknown
- 2013-06-20 BR BR112014031531-0A patent/BR112014031531B1/pt active IP Right Grant
- 2013-06-20 MX MX2014014709A patent/MX354214B/es active IP Right Grant
- 2013-06-20 CA CA2875589A patent/CA2875589C/en active Active
- 2013-06-20 EP EP16162104.0A patent/EP3064494A1/en not_active Withdrawn
- 2013-06-20 RU RU2014148305A patent/RU2638175C2/ru active
- 2013-06-20 UA UAA201412619 patent/UA114196C2/uk unknown
- 2013-06-20 AP AP2014008137A patent/AP2014008137A0/xx unknown
- 2013-06-20 MA MA39259A patent/MA39259B1/fr unknown
- 2013-06-20 IN IN10088DEN2014 patent/IN2014DN10088A/en unknown
- 2013-06-20 CN CN201380033030.6A patent/CN104411697B/zh active Active
- 2013-06-20 CN CN201610570484.2A patent/CN106279102A/zh active Pending
- 2013-06-20 PL PL13733415T patent/PL2864316T3/pl unknown
- 2013-06-20 AU AU2013279109A patent/AU2013279109B2/en active Active
- 2013-06-20 KR KR1020147035069A patent/KR102123708B1/ko active Active
- 2013-06-20 SG SG11201407934UA patent/SG11201407934UA/en unknown
- 2013-06-20 ES ES13733415.7T patent/ES2618939T3/es active Active
- 2013-06-20 SM SM20170142T patent/SMT201700142T1/it unknown
- 2013-06-20 LT LTEP13733415.7T patent/LT2864316T/lt unknown
- 2013-06-20 RS RS20170236A patent/RS55815B1/sr unknown
- 2013-06-20 PE PE2014002451A patent/PE20150670A1/es active IP Right Grant
- 2013-06-20 AP AP2017009693A patent/AP2017009693A0/en unknown
- 2013-06-20 BR BR122016014302-3A patent/BR122016014302B1/pt active IP Right Grant
- 2013-06-20 NZ NZ727045A patent/NZ727045A/en not_active IP Right Cessation
- 2013-06-20 SI SI201330561A patent/SI2864316T1/sl unknown
- 2013-06-21 TW TW106115007A patent/TWI639591B/zh not_active IP Right Cessation
- 2013-06-21 TW TW102122259A patent/TWI588140B/zh not_active IP Right Cessation
-
2014
- 2014-11-25 DO DO2014000268A patent/DOP2014000268A/es unknown
- 2014-11-25 TN TN2014000491A patent/TN2014000491A1/fr unknown
- 2014-12-08 IL IL236131A patent/IL236131A0/en active IP Right Grant
- 2014-12-10 MA MA37666A patent/MA37666B1/fr unknown
- 2014-12-11 CR CR20140571A patent/CR20140571A/es unknown
- 2014-12-11 CL CL2014003374A patent/CL2014003374A1/es unknown
- 2014-12-16 PH PH12014502803A patent/PH12014502803B1/en unknown
- 2014-12-18 NI NI201400146A patent/NI201400146A/es unknown
- 2014-12-18 EC ECIEPI201432215A patent/ECSP14032215A/es unknown
- 2014-12-18 CO CO14278352A patent/CO7151486A2/es unknown
-
2015
- 2015-01-20 ZA ZA2015/00408A patent/ZA201500408B/en unknown
-
2016
- 2016-03-14 PH PH12016500498A patent/PH12016500498A1/en unknown
- 2016-04-29 CR CR20160202A patent/CR20160202A/es unknown
- 2016-06-28 AR ARP160101953A patent/AR105176A2/es unknown
-
2017
- 2017-03-08 ME MEP-2017-61A patent/ME02633B/me unknown
- 2017-03-13 CY CY20171100314T patent/CY1119505T1/el unknown
- 2017-11-03 AU AU2017254965A patent/AU2017254965B2/en not_active Ceased
-
2018
- 2018-02-09 JP JP2018021595A patent/JP6509393B2/ja active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2864316B1 (en) | Camsylate salt of (1r,1'R,4R)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin- 3-yl]-3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine and crystalline forms thereof for the treatment of A[beta]-related pathologies such as e.g. Alzheimer's disease | |
| CA3045957A1 (en) | Monocyclic oga inhibitor compounds | |
| CA3103048A1 (en) | Oga inhibitor compounds | |
| CN104870000A (zh) | 作为bace抑制剂的c5,c6氧杂环稠合的亚胺基噻嗪二氧化物化合物,组合物及其用途 | |
| JP6243921B2 (ja) | Ｂａｃｅ阻害剤 | |
| HUE028672T2 (en) | Iminothiadiazine dioxide compounds such as BACE inhibitors, compositions and their use | |
| US9745324B2 (en) | Iminothiadiazepane dioxide compounds as BACE inhibitors, compositions, and their use | |
| WO2013190301A1 (en) | Cycloalkyl ether compounds and their use as bace inhibitors | |
| TW201422625A (zh) | 二氫－吡啶并－□衍生物之固體形式 | |
| EP4377295B1 (en) | Haloacethydrazides useful as aep inhibitors | |
| CN106068269B (zh) | 氨基噻嗪化合物 | |
| HK1229787A1 (en) | A process for the preparation of a camsylate salt ((1s)-(+)-10 camphorsulfonic acid) of (1r,1'r,4r)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin- 3-yl]-3'h-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine | |
| HK1206349B (en) | Camsylate salt of (1r,1'r,4r)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin- 3-yl]-3'h-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine and crystalline forms thereof for the treatment of a[beta]-related pathologies such as e.g. alzheimer's disease |