EA016447B1 - Соединение альфа-(n-сульфонамидо) ацетамида в качестве ингибитора продуцирования бета амилоидного пептида - Google Patents
Соединение альфа-(n-сульфонамидо) ацетамида в качестве ингибитора продуцирования бета амилоидного пептида Download PDFInfo
- Publication number
- EA016447B1 EA016447B1 EA201000714A EA201000714A EA016447B1 EA 016447 B1 EA016447 B1 EA 016447B1 EA 201000714 A EA201000714 A EA 201000714A EA 201000714 A EA201000714 A EA 201000714A EA 016447 B1 EA016447 B1 EA 016447B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- amino
- trifluoropentanamide
- methyl
- fluoro
- reaction
- Prior art date
Links
- -1 acetamide compound Chemical class 0.000 title abstract description 38
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 title abstract description 16
- 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 title abstract description 15
- 239000003112 inhibitor Substances 0.000 title description 11
- 238000004519 manufacturing process Methods 0.000 title description 10
- 238000000034 method Methods 0.000 claims abstract description 70
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 109
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 12
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 9
- 208000010877 cognitive disease Diseases 0.000 claims description 7
- 201000010374 Down Syndrome Diseases 0.000 claims description 6
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- XEAOPVUAMONVLA-UHFFFAOYSA-N 2-[(4-chlorophenyl)sulfonyl-[[2-fluoro-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-trifluoropentanamide Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)N(C(CCC(F)(F)F)C(=O)N)CC(C(=C1)F)=CC=C1C=1N=CON=1 XEAOPVUAMONVLA-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 abstract description 14
- 230000008569 process Effects 0.000 abstract description 10
- 238000006243 chemical reaction Methods 0.000 description 87
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- 239000000203 mixture Substances 0.000 description 66
- 210000004027 cell Anatomy 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 51
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- 239000007787 solid Substances 0.000 description 37
- 238000004458 analytical method Methods 0.000 description 31
- 241000700159 Rattus Species 0.000 description 29
- 210000004556 brain Anatomy 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 21
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 21
- 239000010410 layer Substances 0.000 description 21
- 239000000725 suspension Substances 0.000 description 20
- 235000012970 cakes Nutrition 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- 239000003814 drug Substances 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 239000003540 gamma secretase inhibitor Substances 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 14
- 238000011534 incubation Methods 0.000 description 12
- 241000282414 Homo sapiens Species 0.000 description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 230000006698 induction Effects 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 230000031709 bromination Effects 0.000 description 8
- 238000005893 bromination reaction Methods 0.000 description 8
- JQXXHWHPUNPDRT-YOPQJBRCSA-N chembl1332716 Chemical compound O([C@](C1=O)(C)O\C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CCN(C)CC1 JQXXHWHPUNPDRT-YOPQJBRCSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- ZZKSAVUXOUDMGW-UHFFFAOYSA-N n-(2-methoxyethyl)benzamide Chemical compound COCCNC(=O)C1=CC=CC=C1 ZZKSAVUXOUDMGW-UHFFFAOYSA-N 0.000 description 8
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 229960001225 rifampicin Drugs 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 8
- YCWDOQVXUVNYLQ-UHFFFAOYSA-N 3-(3-fluoro-4-methylphenyl)-1,2,4-oxadiazole Chemical compound C1=C(F)C(C)=CC=C1C1=NOC=N1 YCWDOQVXUVNYLQ-UHFFFAOYSA-N 0.000 description 7
- SCJCDNUXDWFVFI-UHFFFAOYSA-N 4,4,4-trifluorobutanal Chemical compound FC(F)(F)CCC=O SCJCDNUXDWFVFI-UHFFFAOYSA-N 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- ZBKXTEJUTGXVJL-UHFFFAOYSA-N 3-[4-(bromomethyl)-3-fluorophenyl]-1,2,4-oxadiazole Chemical compound C1=C(CBr)C(F)=CC(C2=NOC=N2)=C1 ZBKXTEJUTGXVJL-UHFFFAOYSA-N 0.000 description 6
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 6
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 6
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000004364 calculation method Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 229940040102 levulinic acid Drugs 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 6
- KUQQONVKIURIQU-UHFFFAOYSA-N 3-fluoro-4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C=C1F KUQQONVKIURIQU-UHFFFAOYSA-N 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- 206010012289 Dementia Diseases 0.000 description 5
- 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 description 5
- 241000282567 Macaca fascicularis Species 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 102000003929 Transaminases Human genes 0.000 description 5
- 108090000340 Transaminases Proteins 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000012452 mother liquor Substances 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 102100029721 DnaJ homolog subfamily B member 1 Human genes 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000866018 Homo sapiens DnaJ homolog subfamily B member 1 Proteins 0.000 description 4
- 101000836383 Homo sapiens Serpin H1 Proteins 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 102100027287 Serpin H1 Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 125000005997 bromomethyl group Chemical group 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 210000004748 cultured cell Anatomy 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 210000003494 hepatocyte Anatomy 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000004811 liquid chromatography Methods 0.000 description 4
- 210000001853 liver microsome Anatomy 0.000 description 4
- 208000002780 macular degeneration Diseases 0.000 description 4
- 238000010907 mechanical stirring Methods 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 4
- 239000002287 radioligand Substances 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 230000008054 signal transmission Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- RDRZEPABDVDQAK-UHFFFAOYSA-N 3-[4-(dibromomethyl)-3-fluorophenyl]-1,2,4-oxadiazole Chemical compound C1=C(C(Br)Br)C(F)=CC(C2=NOC=N2)=C1 RDRZEPABDVDQAK-UHFFFAOYSA-N 0.000 description 3
- ZESZAIOGACKOMB-UHFFFAOYSA-N 4-(bromomethyl)-3-fluorobenzonitrile Chemical compound FC1=CC(C#N)=CC=C1CBr ZESZAIOGACKOMB-UHFFFAOYSA-N 0.000 description 3
- HEXKSBHTYDTPFG-UHFFFAOYSA-N 5,5,5-trifluoro-2-(1-phenylethylamino)pentanenitrile Chemical compound FC(F)(F)CCC(C#N)NC(C)C1=CC=CC=C1 HEXKSBHTYDTPFG-UHFFFAOYSA-N 0.000 description 3
- 102100032187 Androgen receptor Human genes 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 206010054949 Metaplasia Diseases 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 206010064930 age-related macular degeneration Diseases 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 210000001198 duodenum Anatomy 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 210000002175 goblet cell Anatomy 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000015689 metaplastic ossification Effects 0.000 description 3
- 230000003228 microsomal effect Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- HBZBAMXERPYTFS-SECBINFHSA-N (4S)-2-(6,7-dihydro-5H-pyrrolo[3,2-f][1,3]benzothiazol-2-yl)-4,5-dihydro-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)[C@H]1CSC(=N1)c1nc2cc3CCNc3cc2s1 HBZBAMXERPYTFS-SECBINFHSA-N 0.000 description 2
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 2
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 2
- AYAIJXOLOYQFPL-UHFFFAOYSA-N 5,5,5-trifluoro-2-(1-phenylethylamino)pentanamide Chemical compound FC(F)(F)CCC(C(N)=O)NC(C)C1=CC=CC=C1 AYAIJXOLOYQFPL-UHFFFAOYSA-N 0.000 description 2
- FYLZPFSWVMMCQC-UHFFFAOYSA-N 5,5,5-trifluoropentanamide Chemical compound NC(=O)CCCC(F)(F)F FYLZPFSWVMMCQC-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 2
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 102000003849 Cytochrome P450 Human genes 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010015548 Euthanasia Diseases 0.000 description 2
- 108090000698 Formate Dehydrogenases Proteins 0.000 description 2
- 101150092727 KLF10 gene Proteins 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 2
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 102000015499 Presenilins Human genes 0.000 description 2
- 108010050254 Presenilins Proteins 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000005219 aminonitrile group Chemical group 0.000 description 2
- 206010002022 amyloidosis Diseases 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002183 duodenal effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000013213 extrapolation Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 229960002743 glutamine Drugs 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 210000001589 microsome Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
- WIYDEVSKVYFPPV-UHFFFAOYSA-N pentanamide;hydrochloride Chemical compound Cl.CCCCC(N)=O WIYDEVSKVYFPPV-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 2
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 2
- 229960001327 pyridoxal phosphate Drugs 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 102000027257 transmembrane receptors Human genes 0.000 description 2
- 108091008578 transmembrane receptors Proteins 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 1
- VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical compound C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- TZJZWTFULNINJT-UHFFFAOYSA-N 3-[[4-(bromomethyl)-3-fluorophenyl]methyl]-1,2,4-oxadiazole Chemical compound C1=C(CBr)C(F)=CC(CC2=NOC=N2)=C1 TZJZWTFULNINJT-UHFFFAOYSA-N 0.000 description 1
- JNETYVLEGPSOFY-UHFFFAOYSA-N 3-bromopyrrolidine-2,5-dione Chemical compound BrC1CC(=O)NC1=O JNETYVLEGPSOFY-UHFFFAOYSA-N 0.000 description 1
- VKRFUGHXKNNIJO-UHFFFAOYSA-N 4,4,4-trifluorobutan-1-ol Chemical compound OCCCC(F)(F)F VKRFUGHXKNNIJO-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 101150072179 ATP1 gene Proteins 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 101100003366 Arabidopsis thaliana ATPA gene Proteins 0.000 description 1
- 101100171322 Arabidopsis thaliana DSPTP1B gene Proteins 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
- VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 1
- 102100021257 Beta-secretase 1 Human genes 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- JGOSWYKAUGNTMU-UHFFFAOYSA-N Cl.NCCC1=CC=C(CS(F)(=O)=O)C=C1 Chemical compound Cl.NCCC1=CC=C(CS(F)(=O)=O)C=C1 JGOSWYKAUGNTMU-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 101150045737 DUSP4 gene Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 102100027085 Dual specificity protein phosphatase 4 Human genes 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 102100021649 Elongator complex protein 6 Human genes 0.000 description 1
- 241000402754 Erythranthe moschata Species 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 206010019075 Hallucination, visual Diseases 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 1
- 101100065219 Homo sapiens ELP6 gene Proteins 0.000 description 1
- 101000587820 Homo sapiens Selenide, water dikinase 1 Proteins 0.000 description 1
- 101000701815 Homo sapiens Spermidine synthase Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101150097524 Mccc1 gene Proteins 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000836282 Mus musculus Solute carrier organic anion transporter family member 1C1 Proteins 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 101100512343 Pneumocystis carinii MKP2 gene Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 102000012412 Presenilin-1 Human genes 0.000 description 1
- 108010036933 Presenilin-1 Proteins 0.000 description 1
- 102000012419 Presenilin-2 Human genes 0.000 description 1
- 108010036908 Presenilin-2 Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 244000088401 Pyrus pyrifolia Species 0.000 description 1
- 235000001630 Pyrus pyrifolia var culta Nutrition 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 102100037580 Sesquipedalian-1 Human genes 0.000 description 1
- 101710169844 Sesquipedalian-1 Proteins 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 102100027233 Solute carrier organic anion transporter family member 1B1 Human genes 0.000 description 1
- 102100030413 Spermidine synthase Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000007059 Strecker synthesis reaction Methods 0.000 description 1
- 241000512294 Thais Species 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000005377 adsorption chromatography Methods 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
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 1
- 230000003941 amyloidogenesis Effects 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 101150105046 atpI gene Proteins 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000002439 beta secretase inhibitor Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 201000011529 cardiovascular cancer Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000012820 cell cycle checkpoint Effects 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000011979 disease modifying therapy Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 235000021463 dry cake Nutrition 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- 239000002834 estrogen receptor modulator Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000015756 familial Alzheimer disease Diseases 0.000 description 1
- 239000011152 fibreglass Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000011539 homogenization buffer Substances 0.000 description 1
- XPXMKIXDFWLRAA-UHFFFAOYSA-N hydrazinide Chemical compound [NH-]N XPXMKIXDFWLRAA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 102000046701 nicastrin Human genes 0.000 description 1
- 108700022821 nicastrin Proteins 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000004783 oxidative metabolism Effects 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000022256 primary systemic amyloidosis Diseases 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 1
- 102000027483 retinoid hormone receptors Human genes 0.000 description 1
- 108091008679 retinoid hormone receptors Proteins 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000849 selective androgen receptor modulator Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 239000003558 transferase inhibitor Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229950009811 ubenimex Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 229940124648 γ-Secretase Modulator Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98411807P | 2007-10-31 | 2007-10-31 | |
| PCT/US2008/079798 WO2009058552A1 (en) | 2007-10-31 | 2008-10-14 | A novel alpha-(n-sulfonamido)acetamide compound as an inhibitor of beta amyloid peptide production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201000714A1 EA201000714A1 (ru) | 2010-10-29 |
| EA016447B1 true EA016447B1 (ru) | 2012-05-30 |
Family
ID=40193955
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201000714A EA016447B1 (ru) | 2007-10-31 | 2008-10-14 | Соединение альфа-(n-сульфонамидо) ацетамида в качестве ингибитора продуцирования бета амилоидного пептида |
| EA201171439A EA201171439A1 (ru) | 2007-10-31 | 2008-10-14 | Соединение альфа-(n-сульфонамидо)ацетамида в качестве ингибитора продуцирования бета-амилоидного пептида |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201171439A EA201171439A1 (ru) | 2007-10-31 | 2008-10-14 | Соединение альфа-(n-сульфонамидо)ацетамида в качестве ингибитора продуцирования бета-амилоидного пептида |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US8084477B2 (enExample) |
| EP (3) | EP2471769A1 (enExample) |
| JP (1) | JP5460605B2 (enExample) |
| KR (1) | KR20100075575A (enExample) |
| CN (2) | CN101910141B (enExample) |
| AR (1) | AR069135A1 (enExample) |
| AT (1) | ATE502022T1 (enExample) |
| AU (1) | AU2008319122A1 (enExample) |
| BR (1) | BRPI0818837A2 (enExample) |
| CA (1) | CA2704360A1 (enExample) |
| CL (1) | CL2008003271A1 (enExample) |
| CO (1) | CO6270332A2 (enExample) |
| CY (2) | CY1112337T1 (enExample) |
| DE (1) | DE602008005636D1 (enExample) |
| DK (2) | DK2295417T3 (enExample) |
| EA (2) | EA016447B1 (enExample) |
| ES (2) | ES2361283T3 (enExample) |
| HR (2) | HRP20110219T1 (enExample) |
| IL (1) | IL205406A0 (enExample) |
| MX (1) | MX2010004319A (enExample) |
| NZ (1) | NZ584545A (enExample) |
| PE (1) | PE20091394A1 (enExample) |
| PL (2) | PL2295417T3 (enExample) |
| PT (2) | PT2205575E (enExample) |
| SG (2) | SG174044A1 (enExample) |
| SI (2) | SI2295417T1 (enExample) |
| TW (1) | TW200927099A (enExample) |
| WO (1) | WO2009058552A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1465861B1 (en) | 2001-12-20 | 2009-05-06 | Bristol-Myers Squibb Company | Alpha-(n-sulphonamido)acetamide derivatives as beta-amyloid inhibitors |
| US8093276B2 (en) * | 2007-10-31 | 2012-01-10 | Bristol-Myers Squibb Company | Alpha-(N-sulfonamido)acetamide compound as an inhibitor of beta amyloid peptide production |
| US8044077B2 (en) * | 2009-03-19 | 2011-10-25 | Bristol-Myers Squibb Company | Alpha-(N-sulfonamido)acetamide compounds incorporating deuterium as inhibitors of beta amyloid peptide production |
| EP2408450B1 (en) * | 2009-03-19 | 2013-03-13 | Bristol-Myers Squibb Company | Alpha-(n-sulfonamido)acetamide compound as an inhibitor of beta amyloid peptide production |
| US7977362B2 (en) | 2009-03-20 | 2011-07-12 | Bristol-Myers Squibb Company | Alpha-(N-benzenesulfonamido)cycloalkyl derivatives |
| US8252821B2 (en) * | 2009-04-14 | 2012-08-28 | Bristol-Myers Squibb Company | Bioavailable capsule compositions of amorphous alpha-(N-sulfonamido)acetamide compound |
| TW201043269A (en) * | 2009-04-14 | 2010-12-16 | Bristol Myers Squibb Co | Bioavailable compositions of amorphous alpha-(N-sulfonamido)acetamide compound |
| JP5627038B2 (ja) | 2010-03-12 | 2014-11-19 | 日本曹達株式会社 | ピリジン環含有化合物 |
| WO2012040444A2 (en) * | 2010-09-24 | 2012-03-29 | Bristol-Myers Squibb Company | Treatment of patients with incipient alzheimer's disease |
| WO2012069428A1 (en) * | 2010-11-22 | 2012-05-31 | Noscira, S.A. | Bipyridine sulfonamide derivatives for the treatment of neurodegenerative diseases or conditions |
| CN104797584A (zh) | 2012-09-21 | 2015-07-22 | 百时美施贵宝公司 | 作为notch抑制剂的三环杂环化合物 |
| EP2897938B1 (en) | 2012-09-21 | 2017-03-15 | Bristol-Myers Squibb Company | Fluoroalkyl dibenzodiazepinone compounds |
| JP2015534553A (ja) | 2012-09-21 | 2015-12-03 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 置換１，５−ベンゾジアゼピノン化合物 |
| EP2897954B1 (en) | 2012-09-21 | 2016-10-26 | Bristol-Myers Squibb Company | Fluoroalkyl-1,4-benzodiazepinone compounds |
| CN103058913B (zh) * | 2012-12-13 | 2015-09-30 | 江苏弘和药物研发有限公司 | 5-氯异吲哚酮的合成方法 |
| CN104163784B (zh) * | 2014-06-20 | 2019-01-08 | 湖南天地恒一制药有限公司 | 一种奥拉西坦的合成工艺 |
| JP6904612B2 (ja) | 2016-12-16 | 2021-07-21 | パイプライン セラピューティクス， インコーポレイテッド | 蝸牛シナプス障害を処置する方法 |
| WO2018201051A1 (en) | 2017-04-28 | 2018-11-01 | Novartis Ag | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
| EP3615055A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
| CN107935957B (zh) * | 2017-12-02 | 2020-08-21 | 江苏仁明生物科技有限公司 | 一种合成高纯度沙坦侧链ttbb的方法 |
| TWI848951B (zh) | 2018-06-01 | 2024-07-21 | 瑞士商諾華公司 | 針對ｂｃｍａ之結合分子及其用途 |
| CN108640886A (zh) * | 2018-08-01 | 2018-10-12 | 余锋 | 一种作为β-淀粉样肽产生的抑制剂BMS-708163的合成方法 |
| CA3144324A1 (en) | 2019-06-24 | 2020-12-30 | Novartis Ag | Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen |
| CN113466367B (zh) * | 2021-06-25 | 2023-04-14 | 深圳万乐药业有限公司 | 乌苯美司原料药中α-苯乙胺杂质检测方法 |
| CN113816874B (zh) * | 2021-10-30 | 2024-01-26 | 大连双硼医药化工有限公司 | 一种合成4-氰基-2-氟苄醇的工艺方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000050391A1 (en) * | 1999-02-26 | 2000-08-31 | Merck & Co., Inc. | Novel sulfonamide compounds and uses thereof |
| US20020115640A1 (en) * | 2000-11-30 | 2002-08-22 | Claiborne Akiyo K. | Farnesyltransferase inhibitors |
| US6541467B1 (en) * | 2000-04-14 | 2003-04-01 | Corvas International, Inc. | Thrombin inhibitors having a lactam at P3 |
| WO2003053912A1 (en) * | 2001-12-20 | 2003-07-03 | Bristol-Myers Squibb Company | α-(N-SULPHONAMIDO)ACETAMIDE DERIVATIVES AS β-AMYLOID INHIBITORS |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5274094A (en) * | 1990-08-15 | 1993-12-28 | British Bio-Technology Limited | Production of heterobicyclic containing benzene sulfonamides |
| GB9202791D0 (en) * | 1992-02-11 | 1992-03-25 | British Bio Technology | Compounds |
| US5849736A (en) * | 1993-11-24 | 1998-12-15 | The Dupont Merck Pharmaceutical Company | Isoxazoline and isoxazole fibrinogen receptor antagonists |
| CZ291659B6 (cs) * | 1995-11-17 | 2003-04-16 | Warner-Lambert Company | Sulfonamidové inhibitory matricových metaloproteináz |
| PL331338A1 (en) | 1996-07-22 | 1999-07-05 | Monsanto Co | Thiosulphonamidic metaloprotease inhibitors |
| JPH11343279A (ja) | 1998-03-16 | 1999-12-14 | Shionogi & Co Ltd | スルホンアミド誘導体およびそれらを含有するＴＮＦ―α産生抑制剤 |
| HK1038915A1 (zh) | 1999-01-27 | 2002-04-04 | Wyeth Holdings Corporation | 乙炔磺胺硫醇三对甲氧苯基氯乙烯(tace)抑制物 |
| US6313123B1 (en) * | 1999-01-27 | 2001-11-06 | American Cyanamid Company | Acetylenic sulfonamide thiol tace inhibitors |
| DE60239078D1 (de) * | 2001-12-14 | 2011-03-10 | Raytheon Co | Präzise justierte linsenstruktur und eine methode zur herstellung derselben |
| RU2004129278A (ru) * | 2002-02-28 | 2005-06-10 | Астразенека Аб (Se) | Химические соединения |
| ATE362368T1 (de) * | 2003-03-20 | 2007-06-15 | Santhera Pharmaceuticals Ch | Substituierte piperidin- und piperazin-derivative als melanocortin-4 receptor modulatoren |
| TWI336698B (en) * | 2003-03-31 | 2011-02-01 | Wyeth Corp | Fluoro- and trifluoroalkyl-containing heterocyclic sulfonamide inhibitors of beta amyloid production and derivatives thereof |
| US7144894B2 (en) * | 2004-09-23 | 2006-12-05 | Bristol-Myers Squibb Company | Sulfonamide bicyclic compounds |
| RU2008129797A (ru) * | 2006-02-17 | 2010-03-27 | Вайет (Us) | Способы получения сульфонамид-замещенных спиртов и их промежуточных соединений |
| BRPI0707742A2 (pt) * | 2006-02-17 | 2011-05-10 | Wyeth Corp | processo para preparar um composto |
| WO2008112249A1 (en) | 2007-03-13 | 2008-09-18 | Trustees Of Columbia University In The City Of New York | Synergistic interaction of notch-1 inhibitors with glucocorticoids |
| WO2009005688A2 (en) | 2007-06-29 | 2009-01-08 | Trustees Of Columbia University In The City Of New York | Activating mutations in notch-1 |
| US8093276B2 (en) | 2007-10-31 | 2012-01-10 | Bristol-Myers Squibb Company | Alpha-(N-sulfonamido)acetamide compound as an inhibitor of beta amyloid peptide production |
| US8044077B2 (en) * | 2009-03-19 | 2011-10-25 | Bristol-Myers Squibb Company | Alpha-(N-sulfonamido)acetamide compounds incorporating deuterium as inhibitors of beta amyloid peptide production |
-
2008
- 2008-10-10 US US12/249,180 patent/US8084477B2/en active Active
- 2008-10-14 DK DK10190591.7T patent/DK2295417T3/da active
- 2008-10-14 EA EA201000714A patent/EA016447B1/ru not_active IP Right Cessation
- 2008-10-14 PL PL10190591T patent/PL2295417T3/pl unknown
- 2008-10-14 SI SI200830775T patent/SI2295417T1/sl unknown
- 2008-10-14 DE DE602008005636T patent/DE602008005636D1/de active Active
- 2008-10-14 SG SG2011056454A patent/SG174044A1/en unknown
- 2008-10-14 MX MX2010004319A patent/MX2010004319A/es active IP Right Grant
- 2008-10-14 WO PCT/US2008/079798 patent/WO2009058552A1/en not_active Ceased
- 2008-10-14 KR KR1020107009453A patent/KR20100075575A/ko not_active Withdrawn
- 2008-10-14 PT PT08843687T patent/PT2205575E/pt unknown
- 2008-10-14 CN CN2008801240109A patent/CN101910141B/zh not_active Expired - Fee Related
- 2008-10-14 CN CN201210178082XA patent/CN102718689A/zh active Pending
- 2008-10-14 ES ES08843687T patent/ES2361283T3/es active Active
- 2008-10-14 EA EA201171439A patent/EA201171439A1/ru unknown
- 2008-10-14 SG SG2011056447A patent/SG174043A1/en unknown
- 2008-10-14 PT PT10190591T patent/PT2295417E/pt unknown
- 2008-10-14 ES ES10190591T patent/ES2390042T3/es active Active
- 2008-10-14 AU AU2008319122A patent/AU2008319122A1/en not_active Abandoned
- 2008-10-14 PL PL08843687T patent/PL2205575T3/pl unknown
- 2008-10-14 DK DK08843687.8T patent/DK2205575T3/da active
- 2008-10-14 JP JP2010532118A patent/JP5460605B2/ja not_active Expired - Fee Related
- 2008-10-14 HR HR20110219T patent/HRP20110219T1/hr unknown
- 2008-10-14 NZ NZ584545A patent/NZ584545A/en not_active IP Right Cessation
- 2008-10-14 AT AT08843687T patent/ATE502022T1/de active
- 2008-10-14 EP EP12159802A patent/EP2471769A1/en not_active Withdrawn
- 2008-10-14 CA CA2704360A patent/CA2704360A1/en not_active Abandoned
- 2008-10-14 BR BRPI0818837 patent/BRPI0818837A2/pt not_active IP Right Cessation
- 2008-10-14 EP EP10190591A patent/EP2295417B1/en not_active Not-in-force
- 2008-10-14 SI SI200830183T patent/SI2205575T1/sl unknown
- 2008-10-14 EP EP08843687A patent/EP2205575B1/en not_active Not-in-force
- 2008-10-30 CL CL2008003271A patent/CL2008003271A1/es unknown
- 2008-10-30 AR ARP080104770A patent/AR069135A1/es unknown
- 2008-10-31 TW TW097142279A patent/TW200927099A/zh unknown
- 2008-10-31 PE PE2008001866A patent/PE20091394A1/es not_active Application Discontinuation
-
2010
- 2010-04-27 CO CO10049723A patent/CO6270332A2/es not_active Application Discontinuation
- 2010-04-28 IL IL205406A patent/IL205406A0/en unknown
-
2011
- 2011-06-15 CY CY20111100570T patent/CY1112337T1/el unknown
- 2011-11-18 US US13/299,703 patent/US8350084B2/en active Active
-
2012
- 2012-09-04 HR HRP20120703AT patent/HRP20120703T1/hr unknown
- 2012-09-28 CY CY20121100889T patent/CY1113346T1/el unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000050391A1 (en) * | 1999-02-26 | 2000-08-31 | Merck & Co., Inc. | Novel sulfonamide compounds and uses thereof |
| US6541467B1 (en) * | 2000-04-14 | 2003-04-01 | Corvas International, Inc. | Thrombin inhibitors having a lactam at P3 |
| US20020115640A1 (en) * | 2000-11-30 | 2002-08-22 | Claiborne Akiyo K. | Farnesyltransferase inhibitors |
| WO2003053912A1 (en) * | 2001-12-20 | 2003-07-03 | Bristol-Myers Squibb Company | α-(N-SULPHONAMIDO)ACETAMIDE DERIVATIVES AS β-AMYLOID INHIBITORS |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA016447B1 (ru) | Соединение альфа-(n-сульфонамидо) ацетамида в качестве ингибитора продуцирования бета амилоидного пептида | |
| EP2408450B1 (en) | Alpha-(n-sulfonamido)acetamide compound as an inhibitor of beta amyloid peptide production | |
| WO2010107997A1 (en) | Thiophenyl sulfonamides for the treatment of alzheimer's disease | |
| EP2408757B1 (en) | A novel alpha-(n-sulfonamido) acetamide compound incorporating deuterium as inhibitor of beta amyloid peptide production | |
| US8093276B2 (en) | Alpha-(N-sulfonamido)acetamide compound as an inhibitor of beta amyloid peptide production | |
| US9403803B2 (en) | Indole-3-carboxamides as kinase inhibitors | |
| HK1141801B (en) | A novel alpha-(n-sulfonamido)acetamide compound as an inhibitor of beta amyloid peptide production |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM |
|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): RU |