MX2013000514A - Compuestos para recucir la produccion de beta-amiloide. - Google Patents

Info

Publication number

MX2013000514A

MX2013000514A MX2013000514A MX2013000514A MX2013000514A MX 2013000514 A MX2013000514 A MX 2013000514A MX 2013000514 A MX2013000514 A MX 2013000514A MX 2013000514 A MX2013000514 A MX 2013000514A MX 2013000514 A MX2013000514 A MX 2013000514A

Authority

MX

Mexico

Prior art keywords

cyclopenta

methyl

mmol

phenyl

methane

Prior art date

2010-07-15

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 218
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
• 230000009467 reduction Effects 0.000 title claims description 14
• 102000013455 Amyloid beta-Peptides Human genes 0.000 title description 3
• 108010090849 Amyloid beta-Peptides Proteins 0.000 title description 3
• 150000003839 salts Chemical class 0.000 claims abstract description 32
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 27
• 238000011282 treatment Methods 0.000 claims abstract description 17
• 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 6
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 263
• -1 haloCi-6alkyl Chemical group 0.000 claims description 210
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 169
• 229920003026 Acene Polymers 0.000 claims description 124
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 124
• MPJNYKXXSWCRRM-UHFFFAOYSA-N 1-oxa-2,3,4-triazacycloheptadeca-2,4,6,8,10,12,14,16-octaene Chemical compound C1=CC=CC=CC=NN=NOC=CC=CC=C1 MPJNYKXXSWCRRM-UHFFFAOYSA-N 0.000 claims description 121
• 229910052757 nitrogen Inorganic materials 0.000 claims description 87
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 73
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 66
• FVFHZKZQBYHTKR-UHFFFAOYSA-N 1-oxa-2,3,4-triazacyclohexadeca-3,5,7,9,11,13,15-heptaene Chemical compound C=1C=CC=CC=CONN=NC=CC=CC=1 FVFHZKZQBYHTKR-UHFFFAOYSA-N 0.000 claims description 24
• BBTCVLLKSAWIGB-UHFFFAOYSA-N 1-oxa-2,3-diazacycloheptadeca-2,4,6,8,10,12,14,16-octaene Chemical compound C1=CC=CC=CC=CON=NC=CC=CC=C1 BBTCVLLKSAWIGB-UHFFFAOYSA-N 0.000 claims description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
• 229910052739 hydrogen Inorganic materials 0.000 claims description 17
• 125000000217 alkyl group Chemical group 0.000 claims description 15
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
• 208000035475 disorder Diseases 0.000 claims description 13
• 201000002832 Lewy body dementia Diseases 0.000 claims description 12
• 125000001072 heteroaryl group Chemical group 0.000 claims description 12
• 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 11
• 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 claims description 11
• XXVMPTJGGYAODS-UHFFFAOYSA-N 1-oxa-2,3,4,5-tetrazacyclooctadeca-3,5,7,9,11,13,15,17-octaene Chemical compound O1NN=NN=CC=CC=CC=CC=CC=CC=C1 XXVMPTJGGYAODS-UHFFFAOYSA-N 0.000 claims description 10
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 9
• 201000008319 inclusion body myositis Diseases 0.000 claims description 9
• 201000010374 Down Syndrome Diseases 0.000 claims description 7
• SXLTZVXYXZVKIU-UHFFFAOYSA-N O1N=NN=CC=C(C=CC=CC=CC=CC=C1)C#N Chemical compound O1N=NN=CC=C(C=CC=CC=CC=CC=C1)C#N SXLTZVXYXZVKIU-UHFFFAOYSA-N 0.000 claims description 7
• 208000010877 cognitive disease Diseases 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• 208000002780 macular degeneration Diseases 0.000 claims description 6
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
• 239000001301 oxygen Chemical group 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
• 241000124008 Mammalia Species 0.000 claims description 4
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
• 229910052799 carbon Inorganic materials 0.000 claims description 4
• 229910052736 halogen Inorganic materials 0.000 claims description 4
• 150000002367 halogens Chemical class 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
• 125000002560 nitrile group Chemical group 0.000 claims description 3
• 229910052717 sulfur Chemical group 0.000 claims description 3
• 239000011593 sulfur Chemical group 0.000 claims description 3
• 206010028980 Neoplasm Diseases 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• WUIQCJWNFQDSMX-UHFFFAOYSA-N O1NNN=CC=CC=CC=C(C=CC=CC=C1)O Chemical compound O1NNN=CC=CC=CC=C(C=CC=CC=C1)O WUIQCJWNFQDSMX-UHFFFAOYSA-N 0.000 claims 2
• 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims 1
• RPZTVJWNMAAMDR-UHFFFAOYSA-N 1-oxa-2,3,4-triazacyclooctadeca-3,5,7,9,11,13,15,17-octaene Chemical compound N1OC=CC=CC=CC=CC=CC=CC=CN=N1 RPZTVJWNMAAMDR-UHFFFAOYSA-N 0.000 claims 1
• 125000001207 fluorophenyl group Chemical group 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 381
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 364
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 350
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 296
• 239000007787 solid Substances 0.000 description 197
• 238000002360 preparation method Methods 0.000 description 186
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 179
• 238000005481 NMR spectroscopy Methods 0.000 description 166
• 239000011541 reaction mixture Substances 0.000 description 164
• 239000000377 silicon dioxide Substances 0.000 description 157
• 239000000243 solution Substances 0.000 description 152
• 235000019439 ethyl acetate Nutrition 0.000 description 141
• 239000000203 mixture Substances 0.000 description 132
• 239000002904 solvent Substances 0.000 description 132
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 128
• 238000006243 chemical reaction Methods 0.000 description 126
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 125
• 101150041968 CDC13 gene Proteins 0.000 description 117
• 230000014759 maintenance of location Effects 0.000 description 100
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 100
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 98
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 86
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
• 239000012044 organic layer Substances 0.000 description 72
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 63
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
• 238000003818 flash chromatography Methods 0.000 description 59
• 239000012267 brine Substances 0.000 description 57
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 57
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 48
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 48
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 46
• 238000010992 reflux Methods 0.000 description 45
• 239000000725 suspension Substances 0.000 description 43
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 42
• 238000004440 column chromatography Methods 0.000 description 42
• 125000005336 allyloxy group Chemical group 0.000 description 40
• 238000005160 1H NMR spectroscopy Methods 0.000 description 38
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
• 239000000543 intermediate Substances 0.000 description 32
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 29
• 229910052938 sodium sulfate Inorganic materials 0.000 description 29
• 235000011152 sodium sulphate Nutrition 0.000 description 29
• 238000003756 stirring Methods 0.000 description 28
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 27
• 239000000706 filtrate Substances 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 235000019270 ammonium chloride Nutrition 0.000 description 24
• 239000007788 liquid Substances 0.000 description 24
• 238000000034 method Methods 0.000 description 22
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
• 239000008241 heterogeneous mixture Substances 0.000 description 21
• 235000017557 sodium bicarbonate Nutrition 0.000 description 21
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
• 238000004296 chiral HPLC Methods 0.000 description 20
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 19
• 239000010410 layer Substances 0.000 description 19
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
• 229910052751 metal Inorganic materials 0.000 description 18
• 239000002184 metal Substances 0.000 description 18
• 239000012047 saturated solution Substances 0.000 description 18
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 17
• ZRPFJAPZDXQHSM-UHFFFAOYSA-L 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazole;dichloro-[(2-propan-2-yloxyphenyl)methylidene]ruthenium Chemical compound CC(C)OC1=CC=CC=C1C=[Ru](Cl)(Cl)=C1N(C=2C(=CC(C)=CC=2C)C)CCN1C1=C(C)C=C(C)C=C1C ZRPFJAPZDXQHSM-UHFFFAOYSA-L 0.000 description 17
• 229910000024 caesium carbonate Inorganic materials 0.000 description 17
• 238000010898 silica gel chromatography Methods 0.000 description 17
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 16
• 239000012535 impurity Substances 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• 238000002953 preparative HPLC Methods 0.000 description 15
• 238000007142 ring opening reaction Methods 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
• 239000000284 extract Substances 0.000 description 13
• 239000000843 powder Substances 0.000 description 13
• 239000000741 silica gel Substances 0.000 description 13
• 229910002027 silica gel Inorganic materials 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• 150000001336 alkenes Chemical class 0.000 description 12
• 239000007864 aqueous solution Substances 0.000 description 12
• 150000002989 phenols Chemical class 0.000 description 12
• 238000004808 supercritical fluid chromatography Methods 0.000 description 12
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
• YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 11
• 239000002585 base Substances 0.000 description 11
• 238000009472 formulation Methods 0.000 description 11
• 229920006395 saturated elastomer Polymers 0.000 description 11
• 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 10
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 10
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 229910000104 sodium hydride Inorganic materials 0.000 description 10
• 125000003545 alkoxy group Chemical group 0.000 description 9
• 150000001448 anilines Chemical group 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 9
• 239000000651 prodrug Substances 0.000 description 9
• 229940002612 prodrug Drugs 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• 239000003826 tablet Substances 0.000 description 9
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 8
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
• 239000007832 Na2SO4 Substances 0.000 description 8
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 8
• 239000003054 catalyst Substances 0.000 description 8
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 8
• XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 8
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 8
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• 239000012312 sodium hydride Substances 0.000 description 8
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
• YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 7
• BUMGQSCPTLELLS-UHFFFAOYSA-N 2-chloro-5-nitrophenol Chemical compound OC1=CC([N+]([O-])=O)=CC=C1Cl BUMGQSCPTLELLS-UHFFFAOYSA-N 0.000 description 6
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 6
• VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 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
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
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