CN106279102A - 樟脑磺酸盐 - Google Patents
樟脑磺酸盐 Download PDFInfo
- Publication number
- CN106279102A CN106279102A CN201610570484.2A CN201610570484A CN106279102A CN 106279102 A CN106279102 A CN 106279102A CN 201610570484 A CN201610570484 A CN 201610570484A CN 106279102 A CN106279102 A CN 106279102A
- Authority
- CN
- China
- Prior art keywords
- indenes
- hexamethylene
- spiral shell
- methoxyl group
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229950005953 camsilate Drugs 0.000 title claims abstract description 41
- -1 methoxyl group Chemical group 0.000 claims abstract description 13
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims abstract description 3
- 239000002585 base Substances 0.000 claims description 46
- 238000000034 method Methods 0.000 claims description 40
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 6
- 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 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 claims description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- MIOPJNTWMNEORI-OMNKOJBGSA-N [(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical class C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- XJYYTJSLGQZIJU-UHFFFAOYSA-N pyridin-3-yloxyboronic acid Chemical compound OB(O)OC1=CC=CN=C1 XJYYTJSLGQZIJU-UHFFFAOYSA-N 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 2
- YZYKBQUWMPUVEN-UHFFFAOYSA-N zafuleptine Chemical compound OC(=O)CCCCCC(C(C)C)NCC1=CC=C(F)C=C1 YZYKBQUWMPUVEN-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims 2
- 239000003054 catalyst Substances 0.000 claims 2
- 229910052723 transition metal Inorganic materials 0.000 claims 2
- 150000003624 transition metals Chemical class 0.000 claims 2
- GWJSQKNYHPYZRN-UHFFFAOYSA-N 2-methylpropane-2-sulfonamide Chemical compound CC(C)(C)S(N)(=O)=O GWJSQKNYHPYZRN-UHFFFAOYSA-N 0.000 claims 1
- 229910003244 Na2PdCl4 Inorganic materials 0.000 claims 1
- KGYLMXMMQNTWEM-UHFFFAOYSA-J tetrachloropalladium Chemical group Cl[Pd](Cl)(Cl)Cl KGYLMXMMQNTWEM-UHFFFAOYSA-J 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 abstract description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 32
- 230000007170 pathology Effects 0.000 abstract description 32
- 230000007850 degeneration Effects 0.000 abstract description 28
- 201000010099 disease Diseases 0.000 abstract description 28
- 208000024827 Alzheimer disease Diseases 0.000 abstract description 26
- 208000010877 cognitive disease Diseases 0.000 abstract description 24
- 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
- 208000024891 symptom Diseases 0.000 abstract description 17
- 150000003839 salts Chemical class 0.000 abstract description 15
- MUKYLHIZBOASDM-UHFFFAOYSA-N 2-[carbamimidoyl(methyl)amino]acetic acid 2,3,4,5,6-pentahydroxyhexanoic acid Chemical compound NC(=N)N(C)CC(O)=O.OCC(O)C(O)C(O)C(O)C(O)=O MUKYLHIZBOASDM-UHFFFAOYSA-N 0.000 abstract description 14
- 206010008111 Cerebral haemorrhage Diseases 0.000 abstract description 14
- 208000028698 Cognitive impairment Diseases 0.000 abstract description 14
- 206010036631 Presenile dementia Diseases 0.000 abstract description 14
- 241000819233 Tribulus <sea snail> Species 0.000 abstract description 14
- 230000006735 deficit Effects 0.000 abstract description 14
- 206010025482 malaise Diseases 0.000 abstract description 14
- 230000001537 neural effect Effects 0.000 abstract description 14
- 229940047183 tribulus Drugs 0.000 abstract description 14
- 208000000044 Amnesia Diseases 0.000 abstract description 13
- 201000010374 Down Syndrome Diseases 0.000 abstract description 13
- 206010044688 Trisomy 21 Diseases 0.000 abstract description 13
- 208000018737 Parkinson disease Diseases 0.000 abstract description 12
- 231100000863 loss of memory Toxicity 0.000 abstract description 12
- 230000000750 progressive effect Effects 0.000 abstract description 11
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 abstract description 10
- 208000011990 Corticobasal Degeneration Diseases 0.000 abstract description 10
- 208000027061 mild cognitive impairment Diseases 0.000 abstract description 10
- 210000004204 blood vessel Anatomy 0.000 abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 150000001412 amines Chemical class 0.000 abstract description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract 2
- 150000001345 alkine derivatives Chemical class 0.000 abstract 1
- 150000002460 imidazoles Chemical class 0.000 abstract 1
- 150000002469 indenes Chemical class 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 52
- 150000001875 compounds Chemical class 0.000 description 43
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 23
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 23
- 239000003814 drug Substances 0.000 description 22
- 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 17
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 238000011282 treatment Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 13
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 239000000376 reactant Substances 0.000 description 12
- 230000002265 prevention Effects 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000000634 powder X-ray diffraction Methods 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 9
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 9
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 238000005336 cracking Methods 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 230000001629 suppression Effects 0.000 description 8
- 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 7
- 210000004556 brain Anatomy 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 230000008859 change Effects 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 201000004810 Vascular dementia Diseases 0.000 description 5
- 238000013019 agitation Methods 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000008021 deposition Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000001291 vacuum drying Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102100021257 Beta-secretase 1 Human genes 0.000 description 4
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 239000003693 atypical antipsychotic agent Substances 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-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
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 208000035126 Facies Diseases 0.000 description 3
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 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
- 239000007983 Tris buffer Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000006933 amyloid-beta aggregation Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229940025250 camphora Drugs 0.000 description 3
- 239000010238 camphora Substances 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 238000002050 diffraction method Methods 0.000 description 3
- 239000003797 essential amino acid Substances 0.000 description 3
- 235000020776 essential amino acid Nutrition 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000003695 memory enhancer Substances 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
- 239000012044 organic layer Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000758 substrate Substances 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
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 2
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 2
- 0 CO[C@](CC1)CC[C@@]1(Cc1c2cc(*)cc1)C2=O Chemical compound CO[C@](CC1)CC[C@@]1(Cc1c2cc(*)cc1)C2=O 0.000 description 2
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000004317 Lyases Human genes 0.000 description 2
- 108090000856 Lyases Proteins 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
- 206010033799 Paralysis Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 239000002475 cognitive enhancer Substances 0.000 description 2
- 239000013066 combination product Substances 0.000 description 2
- 229940127555 combination product Drugs 0.000 description 2
- 208000013044 corticobasal degeneration disease Diseases 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 235000019820 disodium diphosphate Nutrition 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229960005017 olanzapine Drugs 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000002831 pharmacologic agent Substances 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
- 238000011160 research Methods 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
- 239000000126 substance Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 102000013498 tau Proteins Human genes 0.000 description 2
- 108010026424 tau Proteins Proteins 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000002792 vascular Effects 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
- ZWVMLYRJXORSEP-LURJTMIESA-N (2s)-hexane-1,2,6-triol Chemical compound OCCCC[C@H](O)CO ZWVMLYRJXORSEP-LURJTMIESA-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
- 208000024667 ABeta amyloidosis, Dutch type Diseases 0.000 description 1
- 108091007505 ADAM17 Proteins 0.000 description 1
- 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
- 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000031295 Animal disease Diseases 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
- 208000014644 Brain disease Diseases 0.000 description 1
- 229940122041 Cholinesterase inhibitor Drugs 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
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 102100040243 Microtubule-associated protein tau Human genes 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
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000037280 Trisomy Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- ZALMZWWJQXBYQA-UHFFFAOYSA-N [N].[Cl] Chemical compound [N].[Cl] ZALMZWWJQXBYQA-UHFFFAOYSA-N 0.000 description 1
- 229940056213 abilify Drugs 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940125713 antianxiety drug Drugs 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 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
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 229940068796 clozaril Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000036536 dutch type ABeta amyloidosis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000003203 everyday effect 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
- 230000004927 fusion Effects 0.000 description 1
- 108091007739 gamma-secretases Proteins 0.000 description 1
- 102000038383 gamma-secretases Human genes 0.000 description 1
- 229940003380 geodon Drugs 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000004050 mood stabilizer Substances 0.000 description 1
- 229940127237 mood stabilizer Drugs 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 229950005216 napadisilate Drugs 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- QPUMEZIFDXYGPG-UHFFFAOYSA-N piperazine 1H-pyrrole Chemical class N1CCNCC1.N1C=CC=C1 QPUMEZIFDXYGPG-UHFFFAOYSA-N 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 230000017854 proteolysis 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
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229940106887 risperdal Drugs 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229940035004 seroquel Drugs 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 229940034173 symbyax Drugs 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000003981 vehicle Substances 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)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261662592P | 2012-06-21 | 2012-06-21 | |
| US61/662,592 | 2012-06-21 | ||
| CN201380033030.6A CN104411697B (zh) | 2012-06-21 | 2013-06-20 | 樟脑磺酸盐 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380033030.6A Division CN104411697B (zh) | 2012-06-21 | 2013-06-20 | 樟脑磺酸盐 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106279102A true CN106279102A (zh) | 2017-01-04 |
Family
ID=48746084
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610570484.2A Pending CN106279102A (zh) | 2012-06-21 | 2013-06-20 | 樟脑磺酸盐 |
| CN201380033030.6A Active CN104411697B (zh) | 2012-06-21 | 2013-06-20 | 樟脑磺酸盐 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380033030.6A Active CN104411697B (zh) | 2012-06-21 | 2013-06-20 | 樟脑磺酸盐 |
Country Status (42)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113573709A (zh) * | 2019-03-14 | 2021-10-29 | 阿斯利康(瑞典)有限公司 | 用于体重减轻的兰比斯特 |
Families Citing this family (10)
| 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 |
| WO2013054108A1 (en) | 2011-10-10 | 2013-04-18 | 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 |
| US9000184B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cyclohexane-1,2′-naphthalene-1′,2″-imidazol 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 |
| US9000185B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cycloalkyl ether compounds and their use as BACE inhibitors |
| AR102202A1 (es) | 2014-10-07 | 2017-02-08 | Astrazeneca Ab | Compuestos de oxazol y su uso como inhibidores de bace de oxazol |
| 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 |
| TW201742625A (zh) | 2016-03-15 | 2017-12-16 | 阿斯特捷利康公司 | 組合療法 |
| AR107783A1 (es) | 2016-03-15 | 2018-06-06 | Lilly Co Eli | Terapia de combinación |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010105179A2 (en) * | 2009-03-13 | 2010-09-16 | Vitae Pharmaceuticals, Inc. | Inhibitors of beta-secretase |
| WO2011002408A1 (en) * | 2009-07-02 | 2011-01-06 | Astrazeneca Ab | Novel compounds for treatment of neurodegeneration associated with diseases, such as alzheimer's disease or dementia |
| WO2012087237A1 (en) * | 2010-12-22 | 2012-06-28 | Astrazeneca Ab | Compounds and their use as bace inhibitors |
Family Cites Families (30)
| 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 |
| JP4273406B2 (ja) | 2001-06-01 | 2009-06-03 | 小野薬品工業株式会社 | アルドース還元酵素阻害剤を有効成分とする脱髄性疾患または脱髄を伴う疾患治療剤 |
| US7592348B2 (en) | 2003-12-15 | 2009-09-22 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| DE602005017129D1 (de) | 2004-03-22 | 2009-11-26 | Lilly Co Eli | Pyridyl-derivate und ihre verwendung als mglu5-rezeptorantagonisten |
| SG162790A1 (en) | 2005-06-14 | 2010-07-29 | Schering Corp | Aspartyl protease inhibitors |
| CN101360716A (zh) | 2005-11-21 | 2009-02-04 | 阿斯利康(瑞典)有限公司 | 新颖的2-氨基-咪唑-4-酮化合物及其在制备用于治疗认知缺损、阿尔茨海默病、神经变性和痴呆的药物中的用途 |
| TW200734311A (en) | 2005-11-21 | 2007-09-16 | Astrazeneca Ab | New compounds |
| WO2007076247A1 (en) | 2005-12-21 | 2007-07-05 | 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 |
| US8168641B2 (en) | 2006-06-12 | 2012-05-01 | Schering Corporation | Aspartyl protease inhibitors |
| WO2008076043A1 (en) | 2006-12-20 | 2008-06-26 | Astrazeneca Ab | Novel 2-amino-5,5-diaryl-imidazol-4-ones |
| EP2108018A2 (en) | 2007-02-01 | 2009-10-14 | Glaxo Group Limited | 8-oxa-1,4-diazaspiro [4,5] dec-3-en-1-yl and 1,4,8-triazaspiro [4,5] dec-3-en-1-yl acetamides as glyti transporter inhibitors in treatment of neurological and neuropsychiatric disorders |
| WO2008137139A1 (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 |
| WO2010013794A1 (en) | 2008-07-28 | 2010-02-04 | Eisai R&D Management Co., Ltd. | Spiroaminodihydrothiazine derivatives |
| EP2324032B1 (en) | 2008-08-19 | 2014-10-01 | Vitae Pharmaceuticals, Inc. | Inhibitors of beta-secretase |
| US8426447B2 (en) | 2008-09-11 | 2013-04-23 | Amgen Inc. | Spiro-tricyclic ring compounds as beta-secretase modulators and methods of use |
| TW201105650A (en) | 2009-07-02 | 2011-02-16 | Astrazeneca Ab | New compounds |
| US8889703B2 (en) | 2010-02-24 | 2014-11-18 | Vitae Pharmaceuticals, Inc. | Inhibitors of beta-secretase |
| WO2011123674A1 (en) | 2010-03-31 | 2011-10-06 | Array Biopharma Inc. | Compounds for treating neurodegenerative diseases |
| WO2011130741A1 (en) | 2010-04-16 | 2011-10-20 | Array Biopharma Inc. | Compounds for treating neurodegenerative diseases |
| EP2601197B1 (en) | 2010-08-05 | 2014-06-25 | Amgen Inc. | Amino-iso-indole, amino-aza-iso-indole, amino-dihydroisoquinoline and amino-benzoxazine compounds as beta-secretase modulators and methods of use |
| TW201219400A (en) | 2010-09-24 | 2012-05-16 | Array Biopharma Inc | Compounds for treating neurodegenerative diseases |
| WO2012071458A1 (en) | 2010-11-22 | 2012-05-31 | Array Biopharma Inc. | Heterocyclic inhibitors of beta - secretase for the treatment of neurodegenerative diseases |
| WO2013054108A1 (en) | 2011-10-10 | 2013-04-18 | 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 AU AU2013279109A patent/AU2013279109B2/en active Active
- 2013-06-20 HR HRP20170359TT patent/HRP20170359T1/hr unknown
- 2013-06-20 RS RS20170236A patent/RS55815B1/sr unknown
- 2013-06-20 NZ NZ727045A patent/NZ727045A/en not_active IP Right Cessation
- 2013-06-20 SI SI201330561A patent/SI2864316T1/sl unknown
- 2013-06-20 CN CN201610570484.2A patent/CN106279102A/zh active Pending
- 2013-06-20 CA CA2875589A patent/CA2875589C/en active Active
- 2013-06-20 PL PL13733415T patent/PL2864316T3/pl unknown
- 2013-06-20 SM SM20170142T patent/SMT201700142T1/it unknown
- 2013-06-20 PT PT137334157T patent/PT2864316T/pt unknown
- 2013-06-20 WO PCT/GB2013/051606 patent/WO2013190302A1/en not_active Ceased
- 2013-06-20 MX MX2014014709A patent/MX354214B/es active IP Right Grant
- 2013-06-20 ES ES13733415.7T patent/ES2618939T3/es active Active
- 2013-06-20 MA MA39259A patent/MA39259B1/fr unknown
- 2013-06-20 DK DK13733415.7T patent/DK2864316T3/en active
- 2013-06-20 AP AP2017009693A patent/AP2017009693A0/en unknown
- 2013-06-20 BR BR112014031531-0A patent/BR112014031531B1/pt active IP Right Grant
- 2013-06-20 JP JP2015517850A patent/JP2015520221A/ja active Pending
- 2013-06-20 KR KR1020147035069A patent/KR102123708B1/ko active Active
- 2013-06-20 NZ NZ702742A patent/NZ702742A/en not_active IP Right Cessation
- 2013-06-20 IN IN10088DEN2014 patent/IN2014DN10088A/en unknown
- 2013-06-20 UA UAA201412619 patent/UA114196C2/uk unknown
- 2013-06-20 EP EP16162104.0A patent/EP3064494A1/en not_active Withdrawn
- 2013-06-20 PE PE2014002451A patent/PE20150670A1/es active IP Right Grant
- 2013-06-20 LT LTEP13733415.7T patent/LT2864316T/lt unknown
- 2013-06-20 BR BR122016014302-3A patent/BR122016014302B1/pt active IP Right Grant
- 2013-06-20 HU HUE13733415A patent/HUE033376T2/en unknown
- 2013-06-20 RU RU2014148305A patent/RU2638175C2/ru active
- 2013-06-20 SG SG11201407934UA patent/SG11201407934UA/en unknown
- 2013-06-20 EP EP13733415.7A patent/EP2864316B1/en active Active
- 2013-06-20 CN CN201380033030.6A patent/CN104411697B/zh active Active
- 2013-06-20 AP AP2014008137A patent/AP2014008137A0/xx 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 TN TN2014000491A patent/TN2014000491A1/fr unknown
- 2014-11-25 DO DO2014000268A patent/DOP2014000268A/es 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 CL CL2014003374A patent/CL2014003374A1/es unknown
- 2014-12-11 CR CR20140571A patent/CR20140571A/es unknown
- 2014-12-16 PH PH12014502803A patent/PH12014502803A1/en unknown
- 2014-12-18 CO CO14278352A patent/CO7151486A2/es unknown
- 2014-12-18 EC ECIEPI201432215A patent/ECSP14032215A/es unknown
- 2014-12-18 NI NI201400146A patent/NI201400146A/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
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010105179A2 (en) * | 2009-03-13 | 2010-09-16 | Vitae Pharmaceuticals, Inc. | Inhibitors of beta-secretase |
| WO2011002408A1 (en) * | 2009-07-02 | 2011-01-06 | Astrazeneca Ab | Novel compounds for treatment of neurodegeneration associated with diseases, such as alzheimer's disease or dementia |
| WO2012087237A1 (en) * | 2010-12-22 | 2012-06-28 | Astrazeneca Ab | Compounds and their use as bace inhibitors |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113573709A (zh) * | 2019-03-14 | 2021-10-29 | 阿斯利康(瑞典)有限公司 | 用于体重减轻的兰比斯特 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104411697B (zh) | 樟脑磺酸盐 | |
| JP5686796B2 (ja) | ｃ−Ｍｅｔタンパク質キナーゼのアミノピラゾールトリアゾロチアジアゾール阻害剤 | |
| US8269012B2 (en) | Aminopyrazole triazolothiadiazole inhibitors of c-met protein kinase | |
| JP2012528188A (ja) | ｃ−Ｍｅｔタンパク質キナーゼの阻害剤 | |
| 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 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170104 |