SG186392A1 - Compounds for the reduction of beta-amyloid production - Google Patents

Info

Publication number

SG186392A1

SG186392A1 SG2012093274A SG2012093274A SG186392A1 SG 186392 A1 SG186392 A1 SG 186392A1 SG 2012093274 A SG2012093274 A SG 2012093274A SG 2012093274 A SG2012093274 A SG 2012093274A SG 186392 A1 SG186392 A1 SG 186392A1

Authority

SG

Singapore

Prior art keywords

methyl

cyclopenta

azeno

metheno

mmol

Prior art date

2010-07-15

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 246
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 20
• 230000009467 reduction Effects 0.000 title claims description 17
• 108010090849 Amyloid beta-Peptides Proteins 0.000 title description 2
• 102000013455 Amyloid beta-Peptides Human genes 0.000 title description 2
• 150000003839 salts Chemical class 0.000 claims abstract description 29
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 27
• 238000011282 treatment Methods 0.000 claims abstract description 15
• 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 213
• 229910052757 nitrogen Inorganic materials 0.000 claims description 109
• 238000000034 method Methods 0.000 claims description 27
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• 125000000217 alkyl group Chemical group 0.000 claims description 19
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• 125000001072 heteroaryl group Chemical group 0.000 claims description 14
• 208000035475 disorder Diseases 0.000 claims description 13
• 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 11
• 201000002832 Lewy body dementia Diseases 0.000 claims description 11
• 201000008319 inclusion body myositis Diseases 0.000 claims description 11
• 208000005145 Cerebral amyloid angiopathy Diseases 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
• BFEZZSRZXWNCOQ-UHFFFAOYSA-N N1=C2C(C=NC=CC=COC=CC=CC=3N=C1C=3)=CC=C2 Chemical compound N1=C2C(C=NC=CC=COC=CC=CC=3N=C1C=3)=CC=C2 BFEZZSRZXWNCOQ-UHFFFAOYSA-N 0.000 claims description 8
• 201000010374 Down Syndrome Diseases 0.000 claims description 7
• 208000010877 cognitive disease Diseases 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 239000003937 drug carrier Substances 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
• 125000002496 methyl group Chemical group [H]C([H])([H])* 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
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 5
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• FHGYDTGGUNOESO-UHFFFAOYSA-N 18-(4-fluorophenyl)-10-hydroxy-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene-6-carbonitrile Chemical compound N1C(C=2)=CC=C(C#N)C=2OCC(O)CCNC(C=2CC3)=NC1=NC=2C3C1=CC=C(F)C=C1 FHGYDTGGUNOESO-UHFFFAOYSA-N 0.000 claims description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 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
• AFJYYTUXRGZTLI-UHFFFAOYSA-N 13-methyl-6-(3-methyl-1,2,4-triazol-1-yl)-18-phenyl-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene Chemical compound C1CC=2C(=N3)N(C)CCCCOC(C(=CC=4)N5N=C(C)N=C5)=CC=4NC3=NC=2C1C1=CC=CC=C1 AFJYYTUXRGZTLI-UHFFFAOYSA-N 0.000 claims description 2
• UYQVMWNJHMWEFE-UHFFFAOYSA-N 13-methyl-6-(5-methyl-1,2,4-triazol-1-yl)-18-phenyl-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene Chemical compound C1CC=2C(=N3)N(C)CCCCOC(C(=CC=4)N5C(=NC=N5)C)=CC=4NC3=NC=2C1C1=CC=CC=C1 UYQVMWNJHMWEFE-UHFFFAOYSA-N 0.000 claims description 2
• LDSBODUYGTVSJP-UHFFFAOYSA-N 18-(2,4-difluorophenyl)-13-methyl-6-(3-methyl-1,2,4-triazol-1-yl)-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene Chemical compound C1CC=2C(=N3)N(C)CCCCOC(C(=CC=4)N5N=C(C)N=C5)=CC=4NC3=NC=2C1C1=CC=C(F)C=C1F LDSBODUYGTVSJP-UHFFFAOYSA-N 0.000 claims description 2
• DYCBEOLLILVMRH-UHFFFAOYSA-N 18-(2,4-difluorophenyl)-13-methyl-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene-6-carbonitrile Chemical compound C1CC=2C(=N3)N(C)CCCCOC(C(=CC=4)C#N)=CC=4NC3=NC=2C1C1=CC=C(F)C=C1F DYCBEOLLILVMRH-UHFFFAOYSA-N 0.000 claims description 2
• QSMJRYHHVJROJR-UHFFFAOYSA-N 18-phenyl-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene-6-carbonitrile Chemical compound C1CC=2C(=N3)NCCCCOC(=C4)C(C#N)=CC=C4NC3=NC=2C1C1=CC=CC=C1 QSMJRYHHVJROJR-UHFFFAOYSA-N 0.000 claims description 2
• PSZBZYMYLJGTIV-UHFFFAOYSA-N 19-(4-fluorophenyl)-17-methyl-6-(3-methyl-1,2,4-triazol-1-yl)-8-oxa-2,13,17,21,22-pentazatetracyclo[12.7.1.13,7.015,20]tricosa-1(21),3(23),4,6,14(22),15(20)-hexaene Chemical compound C12=NC(=N3)NC(C=4)=CC=C(N5N=C(C)N=C5)C=4OCCCCNC3=C2CN(C)CC1C1=CC=C(F)C=C1 PSZBZYMYLJGTIV-UHFFFAOYSA-N 0.000 claims description 2
• VZPNBCNIDYHWME-UHFFFAOYSA-N 19-(4-fluorophenyl)-17-methyl-8-oxa-2,13,17,21,22-pentazatetracyclo[12.7.1.13,7.015,20]tricosa-1(21),3(23),4,6,14(22),15(20)-hexaene-6-carbonitrile Chemical compound C12=NC(=N3)NC(C=4)=CC=C(C#N)C=4OCCCCNC3=C2CN(C)CC1C1=CC=C(F)C=C1 VZPNBCNIDYHWME-UHFFFAOYSA-N 0.000 claims description 2
• XUKDMGUYWYRQCF-UHFFFAOYSA-N 6-(4-chloroimidazol-1-yl)-13-methyl-18-phenyl-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene Chemical compound C1CC=2C(=N3)N(C)CCCCOC(C(=CC=4)N5C=C(Cl)N=C5)=CC=4NC3=NC=2C1C1=CC=CC=C1 XUKDMGUYWYRQCF-UHFFFAOYSA-N 0.000 claims description 2
• FXRRQMQWRDATBM-UHFFFAOYSA-N 6-(4-chloroimidazol-1-yl)-18-(2,4-difluorophenyl)-13-methyl-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene Chemical compound C1CC=2C(=N3)N(C)CCCCOC(C(=CC=4)N5C=C(Cl)N=C5)=CC=4NC3=NC=2C1C1=CC=C(F)C=C1F FXRRQMQWRDATBM-UHFFFAOYSA-N 0.000 claims description 2
• 206010028980 Neoplasm Diseases 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 229920000728 polyester Polymers 0.000 claims description 2
• VOYSMHPUJVBEPX-UHFFFAOYSA-N 18-(2,4-difluorophenyl)-6-(3-methyl-1,2,4-triazol-1-yl)-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene Chemical compound N1=C(C)N=CN1C1=CC=C(N2)C=C1OCCCCNC1=NC2=NC2=C1CCC2C1=CC=C(F)C=C1F VOYSMHPUJVBEPX-UHFFFAOYSA-N 0.000 claims 1
• GOQPGHPDMIWJAR-UHFFFAOYSA-N 18-phenyl-8-oxa-2,20,21-triazatetracyclo[12.6.1.13,7.015,19]docosa-1(21),3(22),4,6,14,19-hexaene-6-carbonitrile Chemical compound C1CC=2C(=N3)CCCCCOC(=C4)C(C#N)=CC=C4NC3=NC=2C1C1=CC=CC=C1 GOQPGHPDMIWJAR-UHFFFAOYSA-N 0.000 claims 1
• VRXLUWYIOGBPCL-UHFFFAOYSA-N 6-(3-methyl-1,2,4-triazol-1-yl)-18-phenyl-8-oxa-2,20,21-triazatetracyclo[12.6.1.13,7.015,19]docosa-1(21),3(22),4,6,14,19-hexaene Chemical compound N1=C(C)N=CN1C1=CC=C(N2)C=C1OCCCCCC1=NC2=NC2=C1CCC2C1=CC=CC=C1 VRXLUWYIOGBPCL-UHFFFAOYSA-N 0.000 claims 1
• QJDUZIDYDFIENI-UHFFFAOYSA-N 6-(5-methyl-1,2,4-triazol-1-yl)-18-phenyl-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene Chemical compound CC1=NC=NN1C1=CC=C(N2)C=C1OCCCCNC1=NC2=NC2=C1CCC2C1=CC=CC=C1 QJDUZIDYDFIENI-UHFFFAOYSA-N 0.000 claims 1
• 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 abstract description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 447
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 418
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 386
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 363
• 239000007787 solid Substances 0.000 description 227
• 238000005481 NMR spectroscopy Methods 0.000 description 201
• 239000000243 solution Substances 0.000 description 190
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 189
• 238000002360 preparation method Methods 0.000 description 187
• 239000011541 reaction mixture Substances 0.000 description 175
• 239000000377 silicon dioxide Substances 0.000 description 166
• 239000000203 mixture Substances 0.000 description 165
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 160
• 235000019439 ethyl acetate Nutrition 0.000 description 154
• 230000002829 reductive effect Effects 0.000 description 154
• 239000002904 solvent Substances 0.000 description 141
• 230000014759 maintenance of location Effects 0.000 description 130
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 113
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 109
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 104
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 96
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 90
• 239000000543 intermediate Substances 0.000 description 90
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 83
• 238000006243 chemical reaction Methods 0.000 description 78
• 238000012544 monitoring process Methods 0.000 description 76
• 239000012044 organic layer Substances 0.000 description 75
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 70
• 238000003818 flash chromatography Methods 0.000 description 68
• 239000012267 brine Substances 0.000 description 59
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 59
• 238000004440 column chromatography Methods 0.000 description 56
• 238000005160 1H NMR spectroscopy Methods 0.000 description 55
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 52
• 229910052938 sodium sulfate Inorganic materials 0.000 description 51
• 235000011152 sodium sulphate Nutrition 0.000 description 51
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 50
• 238000010992 reflux Methods 0.000 description 50
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 45
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 42
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 37
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
• 239000002002 slurry Substances 0.000 description 34
• 239000000706 filtrate Substances 0.000 description 32
• 238000003756 stirring Methods 0.000 description 32
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
• -1 without limitation Chemical class 0.000 description 29
• 239000003054 catalyst Substances 0.000 description 25
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
• 239000007788 liquid Substances 0.000 description 24
• 239000000741 silica gel Substances 0.000 description 24
• 229910002027 silica gel Inorganic materials 0.000 description 24
• 235000019270 ammonium chloride Nutrition 0.000 description 23
• 239000002585 base Substances 0.000 description 23
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 23
• 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 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
• 239000010410 layer Substances 0.000 description 22
• 238000004808 supercritical fluid chromatography Methods 0.000 description 22
• 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 21
• 239000008241 heterogeneous mixture Substances 0.000 description 21
• 150000002989 phenols Chemical class 0.000 description 21
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
• 239000012535 impurity Substances 0.000 description 20
• 229910052742 iron Inorganic materials 0.000 description 20
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 19
• 229910000024 caesium carbonate Inorganic materials 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• 229910002091 carbon monoxide Inorganic materials 0.000 description 18
• 229910052801 chlorine Inorganic materials 0.000 description 16
• 238000004305 normal phase HPLC Methods 0.000 description 16
• 238000002953 preparative HPLC Methods 0.000 description 16
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 14
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• 150000001336 alkenes Chemical class 0.000 description 12
• 239000000284 extract Substances 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 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
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 11
• 125000003545 alkoxy group Chemical group 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 238000009472 formulation Methods 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 11
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 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
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
• 239000007864 aqueous solution Substances 0.000 description 10
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• 238000004296 chiral HPLC Methods 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 239000000651 prodrug Substances 0.000 description 9
• 229940002612 prodrug Drugs 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• 239000003826 tablet Substances 0.000 description 9
• VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 8
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 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
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-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
• IBIBCVYBFPAFCI-UHFFFAOYSA-N 1-(2-fluoro-4-nitrophenyl)-3-methyl-1,2,4-triazole Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1F IBIBCVYBFPAFCI-UHFFFAOYSA-N 0.000 description 7
• YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 7
• 150000001448 anilines Chemical group 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 229910052763 palladium Inorganic materials 0.000 description 7
• 229910052697 platinum Inorganic materials 0.000 description 7
• 150000003230 pyrimidines Chemical class 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
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 230000002378 acidificating effect Effects 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 239000012230 colorless oil Substances 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 238000005649 metathesis reaction Methods 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 239000002480 mineral oil Substances 0.000 description 6
• 235000010446 mineral oil Nutrition 0.000 description 6
• 235000019198 oils Nutrition 0.000 description 6
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 6
• 238000010898 silica gel chromatography Methods 0.000 description 6
• TVSZVRDXWYYITJ-UHFFFAOYSA-N 1-(2-fluoro-4-nitrophenyl)-5-methyl-1,2,4-triazole Chemical compound CC1=NC=NN1C1=CC=C([N+]([O-])=O)C=C1F TVSZVRDXWYYITJ-UHFFFAOYSA-N 0.000 description 5
• DZNPHVPBCNZVGW-UHFFFAOYSA-N 2-hydroxy-4-nitrobenzonitrile Chemical compound OC1=CC([N+]([O-])=O)=CC=C1C#N DZNPHVPBCNZVGW-UHFFFAOYSA-N 0.000 description 5
• JOJXKJWLTWFZJZ-UHFFFAOYSA-N 4-amino-2-prop-2-enoxybenzonitrile Chemical compound NC1=CC=C(C#N)C(OCC=C)=C1 JOJXKJWLTWFZJZ-UHFFFAOYSA-N 0.000 description 5
• 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 5
• 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 5
• 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 5
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 239000004202 carbamide Substances 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 230000008878 coupling Effects 0.000 description 5
• 238000010168 coupling process Methods 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• 239000003814 drug Substances 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• VBBUFMFZDHLELS-UHFFFAOYSA-N n-(oxomethylidene)carbamoyl chloride Chemical compound ClC(=O)N=C=O VBBUFMFZDHLELS-UHFFFAOYSA-N 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 238000006798 ring closing metathesis reaction Methods 0.000 description 5
• 125000001424 substituent group Chemical group 0.000 description 5
• GEVIRNFAVXCUMC-UHFFFAOYSA-N tert-butyl n-[3-(2-cyano-5-nitrophenoxy)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCOC1=CC([N+]([O-])=O)=CC=C1C#N GEVIRNFAVXCUMC-UHFFFAOYSA-N 0.000 description 5
• HWOPQDYZGLMPTG-UHFFFAOYSA-N 1-[2-(2-bromoethoxy)-4-nitrophenyl]-3-methyl-1,2,4-triazole Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCCBr HWOPQDYZGLMPTG-UHFFFAOYSA-N 0.000 description 4
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
• XTQDGNUEEGADGZ-UHFFFAOYSA-N 2-(2-aminoethoxy)-4-nitrobenzonitrile Chemical compound NCCOC1=CC([N+]([O-])=O)=CC=C1C#N XTQDGNUEEGADGZ-UHFFFAOYSA-N 0.000 description 4
• JFXQCSMOTMZDAL-UHFFFAOYSA-N 2-(3,4-dihydroxybutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC(O)CO)C(=O)C2=C1 JFXQCSMOTMZDAL-UHFFFAOYSA-N 0.000 description 4
• AJXWMSPTSJWPLB-UHFFFAOYSA-N 2-(4-aminobutoxy)-4-nitrobenzonitrile Chemical compound NCCCCOC1=CC([N+]([O-])=O)=CC=C1C#N AJXWMSPTSJWPLB-UHFFFAOYSA-N 0.000 description 4
• NPELEPAOYMNNRW-UHFFFAOYSA-N 2-phenylcyclopentan-1-one Chemical compound O=C1CCCC1C1=CC=CC=C1 NPELEPAOYMNNRW-UHFFFAOYSA-N 0.000 description 4
• IZINJHSOKSCMHY-UHFFFAOYSA-N 4-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]butan-1-amine Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCCCCN IZINJHSOKSCMHY-UHFFFAOYSA-N 0.000 description 4
• QXBZOFYKXMWVLQ-UHFFFAOYSA-N 4-amino-1-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]butan-2-ol Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCC(O)CCN QXBZOFYKXMWVLQ-UHFFFAOYSA-N 0.000 description 4
• ZLEAZCWQDZUTJD-UHFFFAOYSA-N 4-amino-2-(4-amino-2-hydroxybutoxy)benzonitrile Chemical compound NCCC(O)COC1=CC(N)=CC=C1C#N ZLEAZCWQDZUTJD-UHFFFAOYSA-N 0.000 description 4
• XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 4
• BJEKXKSTRFWUNP-UHFFFAOYSA-N 5-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]pentan-2-amine Chemical compound CC(N)CCCOC1=CC([N+]([O-])=O)=CC=C1N1N=C(C)N=C1 BJEKXKSTRFWUNP-UHFFFAOYSA-N 0.000 description 4
• CNPYJBLTBHXQFR-UHFFFAOYSA-N 7-phenyl-1,5,6,7-tetrahydrocyclopenta[d]pyrimidine-2,4-dione Chemical compound C1CC=2C(=O)NC(=O)NC=2C1C1=CC=CC=C1 CNPYJBLTBHXQFR-UHFFFAOYSA-N 0.000 description 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
• PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 4
• 206010012289 Dementia Diseases 0.000 description 4
• FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 4
• 102100022033 Presenilin-1 Human genes 0.000 description 4
• 108010036933 Presenilin-1 Proteins 0.000 description 4
• 108010036908 Presenilin-2 Proteins 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 235000011054 acetic acid Nutrition 0.000 description 4
• XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 239000011230 binding agent Substances 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 238000000576 coating method Methods 0.000 description 4
• 239000006071 cream Substances 0.000 description 4
• 238000003821 enantio-separation Methods 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 125000000623 heterocyclic group Chemical group 0.000 description 4
• 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 4
• 239000000314 lubricant Substances 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 239000008107 starch Substances 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 239000012258 stirred mixture Substances 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• IOKGWQZQCNXXLD-UHFFFAOYSA-N tert-butyl n-(3-bromopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCBr IOKGWQZQCNXXLD-UHFFFAOYSA-N 0.000 description 4
• 229940045860 white wax Drugs 0.000 description 4
• WVOMRJDDLOTGEY-UHFFFAOYSA-N 1-(cyclopenten-1-yl)-2,4-difluorobenzene Chemical compound FC1=CC(F)=CC=C1C1=CCCC1 WVOMRJDDLOTGEY-UHFFFAOYSA-N 0.000 description 3
• WFQZFUSKFDJLAO-UHFFFAOYSA-N 1-(cyclopenten-1-yl)-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1C1=CCCC1 WFQZFUSKFDJLAO-UHFFFAOYSA-N 0.000 description 3
• VRAMMFJOWAMGFB-UHFFFAOYSA-N 1-chloro-2-[(4-methoxyphenyl)methoxy]-4-nitrobenzene Chemical compound C1=CC(OC)=CC=C1COC1=CC([N+]([O-])=O)=CC=C1Cl VRAMMFJOWAMGFB-UHFFFAOYSA-N 0.000 description 3
• DPBCMCCUWJKAAR-UHFFFAOYSA-N 1-chloro-4-nitro-2-prop-2-enoxybenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(OCC=C)=C1 DPBCMCCUWJKAAR-UHFFFAOYSA-N 0.000 description 3
• YMIFVTXRKIPDLF-UHFFFAOYSA-N 2,4-dichloro-7-(2,4-difluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound FC1=CC(F)=CC=C1C1C(N=C(Cl)N=C2Cl)=C2CC1 YMIFVTXRKIPDLF-UHFFFAOYSA-N 0.000 description 3
• ATWGDJMSPINOIM-UHFFFAOYSA-N 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1C(N=C(Cl)N=C2Cl)=C2CC1 ATWGDJMSPINOIM-UHFFFAOYSA-N 0.000 description 3
• IPFZARHKKQXZPN-UHFFFAOYSA-N 2,4-dichloro-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound C1CC=2C(Cl)=NC(Cl)=NC=2C1C1=CC=CC=C1 IPFZARHKKQXZPN-UHFFFAOYSA-N 0.000 description 3
• LJSXWMIZZJBENZ-UHFFFAOYSA-N 2,4-dichloro-8-(4-fluorophenyl)-6-methyl-7,8-dihydro-5h-pyrido[4,3-d]pyrimidine Chemical compound C12=NC(Cl)=NC(Cl)=C2CN(C)CC1C1=CC=C(F)C=C1 LJSXWMIZZJBENZ-UHFFFAOYSA-N 0.000 description 3
• AILKYSZJGNRQJG-UHFFFAOYSA-N 2-(2,4-difluorophenyl)cyclopentan-1-one Chemical compound FC1=CC(F)=CC=C1C1C(=O)CCC1 AILKYSZJGNRQJG-UHFFFAOYSA-N 0.000 description 3
• ZTDJYPMXTPFPGX-UHFFFAOYSA-N 2-(2-bromoethoxy)-4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C(OCCBr)=C1 ZTDJYPMXTPFPGX-UHFFFAOYSA-N 0.000 description 3
• TXTSYANGGMJBIE-UHFFFAOYSA-N 2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenol Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1O TXTSYANGGMJBIE-UHFFFAOYSA-N 0.000 description 3
• AEIUHWKAYIZWQW-UHFFFAOYSA-N 2-(4-fluorophenyl)cyclopentan-1-one Chemical compound C1=CC(F)=CC=C1C1C(=O)CCC1 AEIUHWKAYIZWQW-UHFFFAOYSA-N 0.000 description 3
• HAWYUAGXPQGNKQ-UHFFFAOYSA-N 2-[3-hydroxy-4-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]butyl]isoindole-1,3-dione Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCC(O)CCN1C(=O)C2=CC=CC=C2C1=O HAWYUAGXPQGNKQ-UHFFFAOYSA-N 0.000 description 3
• NPKZBNAXFQGCDM-UHFFFAOYSA-N 2-[[3-hydroxy-4-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]butyl]carbamoyl]benzoic acid Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCC(O)CCNC(=O)C1=CC=CC=C1C(O)=O NPKZBNAXFQGCDM-UHFFFAOYSA-N 0.000 description 3
• MLNFGMYECUIAJB-UHFFFAOYSA-N 2-[[4-(2-cyano-5-nitrophenoxy)-3-hydroxybutyl]carbamoyl]benzoic acid Chemical compound C=1C([N+]([O-])=O)=CC=C(C#N)C=1OCC(O)CCNC(=O)C1=CC=CC=C1C(O)=O MLNFGMYECUIAJB-UHFFFAOYSA-N 0.000 description 3
• DSGQWLQGHJRCJL-UHFFFAOYSA-N 3-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]propan-1-amine Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCCCN DSGQWLQGHJRCJL-UHFFFAOYSA-N 0.000 description 3
• SRGCMIPYLIVBJK-UHFFFAOYSA-N 3-methyl-1-(4-nitro-2-prop-2-enoxyphenyl)-1,2,4-triazole Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCC=C SRGCMIPYLIVBJK-UHFFFAOYSA-N 0.000 description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
• RASJNMBLIHRANU-UHFFFAOYSA-N 4-(3-methyl-1,2,4-triazol-1-yl)-3-prop-2-enoxyaniline Chemical compound N1=C(C)N=CN1C1=CC=C(N)C=C1OCC=C RASJNMBLIHRANU-UHFFFAOYSA-N 0.000 description 3
• XCLRFOQSEKYDGH-UHFFFAOYSA-N 4-(4-chloroimidazol-1-yl)-3-prop-2-enoxyaniline Chemical compound C=CCOC1=CC(N)=CC=C1N1C=C(Cl)N=C1 XCLRFOQSEKYDGH-UHFFFAOYSA-N 0.000 description 3
• YOYOUXXPUXRWBS-UHFFFAOYSA-N 4-(5-methyl-1,2,4-triazol-1-yl)-3-prop-2-enoxyaniline Chemical compound CC1=NC=NN1C1=CC=C(N)C=C1OCC=C YOYOUXXPUXRWBS-UHFFFAOYSA-N 0.000 description 3
• DEKJPODSYVPCPW-ZGZXFVETSA-N 4-(aminomethyl)-N-[(12E,15S)-17,19-diazatricyclo[14.2.1.02,7]nonadeca-1(18),2,4,6,12,16-hexaen-15-yl]cyclohexane-1-carboxamide Chemical compound NCC1CCC(CC1)C(=O)N[C@H]1C\C=C\CCCCc2ccccc2-c2cnc1[nH]2 DEKJPODSYVPCPW-ZGZXFVETSA-N 0.000 description 3
• LCLAVZUYWBNMHX-UHFFFAOYSA-N 4-amino-2-(4-aminobutoxy)benzonitrile Chemical compound NCCCCOC1=CC(N)=CC=C1C#N LCLAVZUYWBNMHX-UHFFFAOYSA-N 0.000 description 3
• TVNKQKZCZCVDPI-UHFFFAOYSA-N 4-amino-2-[4-[[2-chloro-8-(4-fluorophenyl)-6-methyl-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]butoxy]benzonitrile Chemical compound C12=NC(Cl)=NC(NCCCCOC=3C(=CC=C(N)C=3)C#N)=C2CN(C)CC1C1=CC=C(F)C=C1 TVNKQKZCZCVDPI-UHFFFAOYSA-N 0.000 description 3
• SZWCGBPBGLUVGF-UHFFFAOYSA-N 4-chloro-1-(4-nitro-2-prop-2-enoxyphenyl)imidazole Chemical compound C=CCOC1=CC([N+](=O)[O-])=CC=C1N1C=C(Cl)N=C1 SZWCGBPBGLUVGF-UHFFFAOYSA-N 0.000 description 3
• HLPXACVEKAQVFI-UHFFFAOYSA-N 4-nitro-2-prop-2-enoxybenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C(OCC=C)=C1 HLPXACVEKAQVFI-UHFFFAOYSA-N 0.000 description 3
• BQRBAXFOPZRMCU-UHFFFAOYSA-N 5-chloro-1h-imidazole Chemical compound ClC1=CN=CN1 BQRBAXFOPZRMCU-UHFFFAOYSA-N 0.000 description 3
• PIFQOQFSDBETDM-UHFFFAOYSA-N 5-methyl-1-(4-nitro-2-prop-2-enoxyphenyl)-1,2,4-triazole Chemical compound CC1=NC=NN1C1=CC=C([N+]([O-])=O)C=C1OCC=C PIFQOQFSDBETDM-UHFFFAOYSA-N 0.000 description 3
• NESKBLJDFFAUSV-UHFFFAOYSA-N 7-(4-fluorophenyl)-1,5,6,7-tetrahydrocyclopenta[d]pyrimidine-2,4-dione Chemical compound C1=CC(F)=CC=C1C1C(NC(=O)NC2=O)=C2CC1 NESKBLJDFFAUSV-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• 208000037259 Amyloid Plaque Diseases 0.000 description 3
• QYMSJXKEHPYVSI-UHFFFAOYSA-N C1=CC=COC=CC=CC2=CC(=N2)N=C3C=CC=C3C=C1 Chemical compound C1=CC=COC=CC=CC2=CC(=N2)N=C3C=CC=C3C=C1 QYMSJXKEHPYVSI-UHFFFAOYSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 102100022036 Presenilin-2 Human genes 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 3
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
• 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 238000006555 catalytic reaction Methods 0.000 description 3
• 238000005660 chlorination reaction Methods 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000011248 coating agent Substances 0.000 description 3
• 238000009833 condensation Methods 0.000 description 3
• 230000005494 condensation Effects 0.000 description 3
• 125000004093 cyano group Chemical group *C#N 0.000 description 3
• CXMYOMKBXNPDIW-UHFFFAOYSA-N cyclopenten-1-ylbenzene Chemical compound C1CCC=C1C1=CC=CC=C1 CXMYOMKBXNPDIW-UHFFFAOYSA-N 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 150000002170 ethers Chemical class 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 150000002678 macrocyclic compounds Chemical class 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• KJZJDAKXQBLYAO-UHFFFAOYSA-N n'-[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]ethane-1,2-diamine Chemical compound C1CC=2C(NCCN)=NC(Cl)=NC=2C1C1=CC=C(F)C=C1 KJZJDAKXQBLYAO-UHFFFAOYSA-N 0.000 description 3
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
• QUTUBFXRMRBJTL-UHFFFAOYSA-N n-methyl-3-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]propan-1-amine Chemical compound CNCCCOC1=CC([N+]([O-])=O)=CC=C1N1N=C(C)N=C1 QUTUBFXRMRBJTL-UHFFFAOYSA-N 0.000 description 3
• QKWULNOMHKBBLA-UHFFFAOYSA-N n-methylbut-3-en-1-amine Chemical compound CNCCC=C QKWULNOMHKBBLA-UHFFFAOYSA-N 0.000 description 3
• IOXXVNYDGIXMIP-UHFFFAOYSA-N n-methylprop-2-en-1-amine Chemical compound CNCC=C IOXXVNYDGIXMIP-UHFFFAOYSA-N 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
• 239000006072 paste Substances 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• 239000002244 precipitate Substances 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 3
• GKGFAEREWWZBKY-UHFFFAOYSA-N tert-butyl n-(4-bromobutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCBr GKGFAEREWWZBKY-UHFFFAOYSA-N 0.000 description 3
• NRRUAIDJASETCY-UHFFFAOYSA-N tert-butyl n-(5-hydroxypentan-2-yl)carbamate Chemical compound OCCCC(C)NC(=O)OC(C)(C)C NRRUAIDJASETCY-UHFFFAOYSA-N 0.000 description 3
• JVIVWBITSRZQSH-UHFFFAOYSA-N tert-butyl n-[2-(2-cyano-5-nitrophenoxy)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOC1=CC([N+]([O-])=O)=CC=C1C#N JVIVWBITSRZQSH-UHFFFAOYSA-N 0.000 description 3
• PUOXBURURCJDED-UHFFFAOYSA-N tert-butyl n-[3-(2-chloro-5-nitrophenoxy)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCOC1=CC([N+]([O-])=O)=CC=C1Cl PUOXBURURCJDED-UHFFFAOYSA-N 0.000 description 3
• OOLUUVAKNLOBAP-UHFFFAOYSA-N tert-butyl n-[4-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]butyl]carbamate Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCCCCNC(=O)OC(C)(C)C OOLUUVAKNLOBAP-UHFFFAOYSA-N 0.000 description 3
• 238000011200 topical administration Methods 0.000 description 3
• 238000010626 work up procedure Methods 0.000 description 3
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
• RUBQQRMAWLSCCJ-UHFFFAOYSA-N 1,2-difluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1 RUBQQRMAWLSCCJ-UHFFFAOYSA-N 0.000 description 2
• 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 description 2
• 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 description 2
• RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
• HRAHIDDUGDBJQT-UHFFFAOYSA-N 2-[2-[2-[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]ethylamino]ethoxy]-4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C(OCCNCCC=2C=3CCC(C=3N=C(Cl)N=2)C=2C=CC(F)=CC=2)=C1 HRAHIDDUGDBJQT-UHFFFAOYSA-N 0.000 description 2
• MIPCGWBBHITITI-UHFFFAOYSA-N 2-[2-[2-[[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]ethyl-methylamino]ethoxy]-4-nitrobenzonitrile Chemical compound C=1C([N+]([O-])=O)=CC=C(C#N)C=1OCCN(C)CCNC(C=1CC2)=NC(Cl)=NC=1C2C1=CC=C(F)C=C1 MIPCGWBBHITITI-UHFFFAOYSA-N 0.000 description 2
• KTHIGOYNYOEIOH-UHFFFAOYSA-N 2-[2-[2-[[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]ethylamino]ethoxy]-4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C(OCCNCCNC=2C=3CCC(C=3N=C(Cl)N=2)C=2C=CC(F)=CC=2)=C1 KTHIGOYNYOEIOH-UHFFFAOYSA-N 0.000 description 2
• DANWYCOLCCEQLQ-UHFFFAOYSA-N 2-[3-(methylamino)propoxy]-4-nitrobenzonitrile Chemical compound CNCCCOC1=CC([N+]([O-])=O)=CC=C1C#N DANWYCOLCCEQLQ-UHFFFAOYSA-N 0.000 description 2
• DAJJPXCSJPKURF-UHFFFAOYSA-N 2-[3-[(2-chloro-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl)-methylamino]propoxy]-4-nitrobenzonitrile Chemical compound N=1C(Cl)=NC=2C(C=3C=CC=CC=3)CCC=2C=1N(C)CCCOC1=CC([N+]([O-])=O)=CC=C1C#N DAJJPXCSJPKURF-UHFFFAOYSA-N 0.000 description 2
• IMTLNPADDZEMQW-UHFFFAOYSA-N 2-[4-(1,3-dioxoisoindol-2-yl)-2-hydroxybutoxy]-4-nitrobenzonitrile Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC(O)COC1=CC([N+]([O-])=O)=CC=C1C#N IMTLNPADDZEMQW-UHFFFAOYSA-N 0.000 description 2
• RKMFZRNAEMUFBL-UHFFFAOYSA-N 2-[4-[(2-chloro-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl)amino]butoxy]-4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C(OCCCCNC=2C=3CCC(C=3N=C(Cl)N=2)C=2C=CC=CC=2)=C1 RKMFZRNAEMUFBL-UHFFFAOYSA-N 0.000 description 2
• FLWGRLILHGXFEP-UHFFFAOYSA-N 2-chloro-7-(4-fluorophenyl)-7-methyl-n-prop-2-enyl-5,6-dihydrocyclopenta[d]pyrimidin-4-amine Chemical compound C1CC(C(=NC(Cl)=N2)NCC=C)=C2C1(C)C1=CC=C(F)C=C1 FLWGRLILHGXFEP-UHFFFAOYSA-N 0.000 description 2
• UQGOZGGBPVVAFY-UHFFFAOYSA-N 2-chloro-8-(4-fluorophenyl)-6-methyl-n-[4-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]butyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C12=NC(Cl)=NC(NCCCCOC=3C(=CC=C(C=3)[N+]([O-])=O)N3N=C(C)N=C3)=C2CN(C)CC1C1=CC=C(F)C=C1 UQGOZGGBPVVAFY-UHFFFAOYSA-N 0.000 description 2
• KAPCIXQNVQHZLW-UHFFFAOYSA-N 2-chloro-8-(4-fluorophenyl)-n,6-dimethyl-n-prop-2-enyl-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1N(C)CC=2C(N(CC=C)C)=NC(Cl)=NC=2C1C1=CC=C(F)C=C1 KAPCIXQNVQHZLW-UHFFFAOYSA-N 0.000 description 2
• RKGWRWSLZKJFCQ-UHFFFAOYSA-N 2-chloro-n-[2-[2-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]ethoxy]ethyl]-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C=1C([N+](=O)[O-])=CC=C(N2C=C(Cl)N=C2)C=1OCCOCCNC(C=1CC2)=NC(Cl)=NC=1C2C1=CC=CC=C1 RKGWRWSLZKJFCQ-UHFFFAOYSA-N 0.000 description 2
• KZHVOUROLDFILE-UHFFFAOYSA-N 2-chloro-n-[3-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]propyl]-n-methyl-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C(Cl)=NC=2C(C=3C=CC=CC=3)CCC=2C=1N(C)CCCOC1=CC([N+]([O-])=O)=CC=C1N1C=NC(Cl)=C1 KZHVOUROLDFILE-UHFFFAOYSA-N 0.000 description 2
• LGIOLLIKWYLWKG-UHFFFAOYSA-N 3-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]propan-1-amine Chemical compound NCCCOC1=CC([N+]([O-])=O)=CC=C1N1C=C(Cl)N=C1 LGIOLLIKWYLWKG-UHFFFAOYSA-N 0.000 description 2
• ASVKKRLMJCWVQF-UHFFFAOYSA-N 3-buten-1-amine Chemical compound NCCC=C ASVKKRLMJCWVQF-UHFFFAOYSA-N 0.000 description 2
• BLNPEJXSNSBBNM-UHFFFAOYSA-N 4-(1,2,4-triazol-1-yl)aniline Chemical class C1=CC(N)=CC=C1N1N=CN=C1 BLNPEJXSNSBBNM-UHFFFAOYSA-N 0.000 description 2
• FBHVSFJVUUTLCO-UHFFFAOYSA-N 4-[[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]-1-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]butan-2-ol Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCC(O)CCNC1=NC(Cl)=NC2=C1CCC2C1=CC=C(F)C=C1 FBHVSFJVUUTLCO-UHFFFAOYSA-N 0.000 description 2
• LVOASPZGXNAHJI-UHFFFAOYSA-N 4-imidazol-1-ylaniline Chemical class C1=CC(N)=CC=C1N1C=NC=C1 LVOASPZGXNAHJI-UHFFFAOYSA-N 0.000 description 2
• IMHGAHPREAELBI-UHFFFAOYSA-N 5-(difluoromethyl)-1h-imidazole Chemical compound FC(F)C1=CNC=N1 IMHGAHPREAELBI-UHFFFAOYSA-N 0.000 description 2
• NCVIZLODYQBMOK-UHFFFAOYSA-N 7-(2,4-difluorophenyl)-1,5,6,7-tetrahydrocyclopenta[d]pyrimidine-2,4-dione Chemical compound FC1=CC(F)=CC=C1C1C(NC(=O)NC2=O)=C2CC1 NCVIZLODYQBMOK-UHFFFAOYSA-N 0.000 description 2
• YGTYFYAWSFXSOW-UHFFFAOYSA-N 7-phenyl-6,7-dihydro-5h-cyclopenta[e][1,3]oxazine-2,4-dione Chemical compound C1=2OC(=O)NC(=O)C=2CCC1C1=CC=CC=C1 YGTYFYAWSFXSOW-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 2
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 101100509438 Leishmania major NSNH gene Proteins 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• BTANRVKWQNVYAZ-UHFFFAOYSA-N Sec-butyl alcohol Natural products CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
• 238000005903 acid hydrolysis reaction Methods 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 150000003973 alkyl amines Chemical class 0.000 description 2
• 125000003282 alkyl amino group Chemical group 0.000 description 2
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 150000004792 aryl magnesium halides Chemical class 0.000 description 2
• GKMQWTVAAMITHR-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O.CCC(C)O GKMQWTVAAMITHR-UHFFFAOYSA-N 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 230000003197 catalytic effect Effects 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
• 239000003086 colorant Substances 0.000 description 2
• 239000006184 cosolvent Substances 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• 125000004663 dialkyl amino group Chemical group 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 238000006073 displacement reaction Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• OMJYLXJXXQVFBT-UHFFFAOYSA-N ethyl 3-[(3-ethoxy-3-oxopropyl)amino]-2-(4-fluorophenyl)propanoate Chemical compound CCOC(=O)CCNCC(C(=O)OCC)C1=CC=C(F)C=C1 OMJYLXJXXQVFBT-UHFFFAOYSA-N 0.000 description 2
• IFYPGGQCKJUNTN-UHFFFAOYSA-N ethyl 3-amino-2-(4-fluorophenyl)propanoate Chemical compound CCOC(=O)C(CN)C1=CC=C(F)C=C1 IFYPGGQCKJUNTN-UHFFFAOYSA-N 0.000 description 2
• JLNXZNUKFXBSRP-UHFFFAOYSA-N ethyl 5-(4-fluorophenyl)-1-methyl-4-oxopiperidine-3-carboxylate Chemical compound O=C1C(C(=O)OCC)CN(C)CC1C1=CC=C(F)C=C1 JLNXZNUKFXBSRP-UHFFFAOYSA-N 0.000 description 2
• 238000011049 filling Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 210000004558 lewy body Anatomy 0.000 description 2
• 239000002502 liposome Substances 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
• JAUWOQLHLFMTON-UHFFFAOYSA-M magnesium;but-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]CC=C JAUWOQLHLFMTON-UHFFFAOYSA-M 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• SZWAGCIPFSMRIY-UHFFFAOYSA-N n'-[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-n-methylethane-1,2-diamine Chemical compound C1CC=2C(NCCNC)=NC(Cl)=NC=2C1C1=CC=C(F)C=C1 SZWAGCIPFSMRIY-UHFFFAOYSA-N 0.000 description 2
• YCAHEERIHUQUHA-UHFFFAOYSA-N n-[5-[5-amino-2-(3-methyl-1,2,4-triazol-1-yl)phenoxy]pentan-2-yl]-2-chloro-7-(2,4-difluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C(Cl)=NC=2C(C=3C(=CC(F)=CC=3)F)CCC=2C=1NC(C)CCCOC1=CC(N)=CC=C1N1C=NC(C)=N1 YCAHEERIHUQUHA-UHFFFAOYSA-N 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• DRGCXLJWMQGVJA-UHFFFAOYSA-N pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CN=C1 DRGCXLJWMQGVJA-UHFFFAOYSA-N 0.000 description 2
• 210000003583 retinal pigment epithelium Anatomy 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 238000009491 slugging Methods 0.000 description 2
• 229940079827 sodium hydrogen sulfite Drugs 0.000 description 2
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 230000002269 spontaneous effect Effects 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 238000010189 synthetic method Methods 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• LIYMTLVBAVHPBU-UHFFFAOYSA-N tert-butyl n-(4-hydroxybutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCO LIYMTLVBAVHPBU-UHFFFAOYSA-N 0.000 description 2
• SXRFLQCZSBFSJK-UHFFFAOYSA-N tert-butyl n-(5-bromopentan-2-yl)carbamate Chemical compound BrCCCC(C)NC(=O)OC(C)(C)C SXRFLQCZSBFSJK-UHFFFAOYSA-N 0.000 description 2
• RLPDTTXEJGDXSM-UHFFFAOYSA-N tert-butyl n-[2-[2-(2-chloro-5-nitrophenoxy)ethoxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOCCOC1=CC([N+]([O-])=O)=CC=C1Cl RLPDTTXEJGDXSM-UHFFFAOYSA-N 0.000 description 2
• SPQHPQRYQSIONS-UHFFFAOYSA-N tert-butyl n-[2-[2-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]ethoxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOCCOC1=CC([N+]([O-])=O)=CC=C1N1C=C(Cl)N=C1 SPQHPQRYQSIONS-UHFFFAOYSA-N 0.000 description 2
• SFQNGWBUTJUOGS-UHFFFAOYSA-N tert-butyl n-[3-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]propyl]carbamate Chemical compound N1=C(C)N=CN1C1=CC=C([N+]([O-])=O)C=C1OCCCNC(=O)OC(C)(C)C SFQNGWBUTJUOGS-UHFFFAOYSA-N 0.000 description 2
• IMRGDAMIJUWQRK-UHFFFAOYSA-N tert-butyl n-[3-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]propyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CCCOC1=CC([N+]([O-])=O)=CC=C1N1C=C(Cl)N=C1 IMRGDAMIJUWQRK-UHFFFAOYSA-N 0.000 description 2
• FUENKDDAMVWJAE-UHFFFAOYSA-N tert-butyl n-[3-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCOC1=CC([N+]([O-])=O)=CC=C1N1C=C(Cl)N=C1 FUENKDDAMVWJAE-UHFFFAOYSA-N 0.000 description 2
• VHZVNHFHYJOROP-UHFFFAOYSA-N tert-butyl n-[5-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]pentan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)CCCOC1=CC([N+]([O-])=O)=CC=C1N1N=C(C)N=C1 VHZVNHFHYJOROP-UHFFFAOYSA-N 0.000 description 2
• MZYNQTOPYXEUDX-UHFFFAOYSA-N tert-butyl n-but-3-enyl-n-methylcarbamate Chemical compound C=CCCN(C)C(=O)OC(C)(C)C MZYNQTOPYXEUDX-UHFFFAOYSA-N 0.000 description 2
• YWSXTMBDIBZHBB-UHFFFAOYSA-N tert-butyl n-but-3-enylcarbamate Chemical compound CC(C)(C)OC(=O)NCCC=C YWSXTMBDIBZHBB-UHFFFAOYSA-N 0.000 description 2
• JOKLDTURLSDAPI-UHFFFAOYSA-N tert-butyl n-methyl-n-[3-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]propyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C)CCCOC1=CC([N+]([O-])=O)=CC=C1N1N=C(C)N=C1 JOKLDTURLSDAPI-UHFFFAOYSA-N 0.000 description 2
• 150000003509 tertiary alcohols Chemical class 0.000 description 2
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• FBKFDSUZBVDZIX-FFGDOFBPSA-N (4s)-4-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-acetamido-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-2-methylpropanoyl]amino]-3-[4-(phosphonomethyl)phenyl]propanoyl]amino]-3-(6-chloro-1h-indol-3-yl)propanoyl]amino]-5-[[1-[[(2s)-1-amino-4-meth Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NC(C)(C)C(=O)N[C@@H](CC=1C=CC(CP(O)(O)=O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=C(Cl)C=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)NC1(CC1)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(C)=O)C1=CC=CC=C1 FBKFDSUZBVDZIX-FFGDOFBPSA-N 0.000 description 1
• 239000001124 (E)-prop-1-ene-1,2,3-tricarboxylic acid Substances 0.000 description 1
• XGCDBGRZEKYHNV-UHFFFAOYSA-N 1,1-bis(diphenylphosphino)methane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CP(C=1C=CC=CC=1)C1=CC=CC=C1 XGCDBGRZEKYHNV-UHFFFAOYSA-N 0.000 description 1
• GIGRWGTZFONRKA-UHFFFAOYSA-N 1-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CBr)C=C1 GIGRWGTZFONRKA-UHFFFAOYSA-N 0.000 description 1
• ZEICUETXTGFVCE-UHFFFAOYSA-N 1-[2-[(4-methoxyphenyl)methoxy]-4-nitrophenyl]-3-methyl-1,2,4-triazole Chemical compound C1=CC(OC)=CC=C1COC1=CC([N+]([O-])=O)=CC=C1N1N=C(C)N=C1 ZEICUETXTGFVCE-UHFFFAOYSA-N 0.000 description 1
• IXSGUTOUTHCMQB-UHFFFAOYSA-N 1-[2-[(4-methoxyphenyl)methoxy]-4-nitrophenyl]-5-methyl-1,2,4-triazole Chemical compound C1=CC(OC)=CC=C1COC1=CC([N+]([O-])=O)=CC=C1N1C(C)=NC=N1 IXSGUTOUTHCMQB-UHFFFAOYSA-N 0.000 description 1
• UGKWRFUVWKZLEV-UHFFFAOYSA-N 1-[5-amino-2-(3-methyl-1,2,4-triazol-1-yl)phenoxy]-4-[[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]butan-2-ol Chemical compound N1=C(C)N=CN1C1=CC=C(N)C=C1OCC(O)CCNC1=NC(Cl)=NC2=C1CCC2C1=CC=C(F)C=C1 UGKWRFUVWKZLEV-UHFFFAOYSA-N 0.000 description 1
• JXIJUAWSDBACEB-UHFFFAOYSA-N 1-chloro-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1Cl JXIJUAWSDBACEB-UHFFFAOYSA-N 0.000 description 1
• XUCYJGMIICONES-UHFFFAOYSA-N 1-fluoro-2-methyl-4-nitrobenzene Chemical compound CC1=CC([N+]([O-])=O)=CC=C1F XUCYJGMIICONES-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• NPGVJCMVNQBEDU-UHFFFAOYSA-N 1-oxa-6,10,12-triazacycloheptadeca-2,4,6,8,10,12,14,16-octaene Chemical compound C1=CC=NC=NC=CC=NC=CC=COC=C1 NPGVJCMVNQBEDU-UHFFFAOYSA-N 0.000 description 1
• VZOPVKZLLGMDDG-UHFFFAOYSA-N 1-oxido-4-phenylpyridin-1-ium Chemical compound C1=C[N+]([O-])=CC=C1C1=CC=CC=C1 VZOPVKZLLGMDDG-UHFFFAOYSA-N 0.000 description 1
• LTFBFZBWUKWXID-UHFFFAOYSA-N 1h-cyclopenta[d]pyrimidine Chemical class N1=CNC2=CC=CC2=C1 LTFBFZBWUKWXID-UHFFFAOYSA-N 0.000 description 1
• UIZISHZMFCCGIR-UHFFFAOYSA-N 2,4-dichloro-7-(4-fluorophenyl)-7-methyl-5,6-dihydrocyclopenta[d]pyrimidine Chemical compound C1CC(C(=NC(Cl)=N2)Cl)=C2C1(C)C1=CC=C(F)C=C1 UIZISHZMFCCGIR-UHFFFAOYSA-N 0.000 description 1
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
• JHQBLYITVCBGTO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetonitrile Chemical compound FC1=CC=C(CC#N)C=C1 JHQBLYITVCBGTO-UHFFFAOYSA-N 0.000 description 1
• MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
• GQCGQDPIGVWRNZ-UHFFFAOYSA-N 2-[3-[[2-chloro-7-(2,4-difluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-methylamino]propoxy]-4-nitrobenzonitrile Chemical compound N=1C(Cl)=NC=2C(C=3C(=CC(F)=CC=3)F)CCC=2C=1N(C)CCCOC1=CC([N+]([O-])=O)=CC=C1C#N GQCGQDPIGVWRNZ-UHFFFAOYSA-N 0.000 description 1
• DWKNOLCXIFYNFV-HSZRJFAPSA-N 2-[[(2r)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-n,n,6-trimethylpyridine-4-carboxamide Chemical compound CN(C)C(=O)C1=CC(C)=NC(NC(=O)[C@@H]2N(C(=O)CC2)C2CCN(CC=3C=C(C)C(Cl)=CC=3)CC2)=C1 DWKNOLCXIFYNFV-HSZRJFAPSA-N 0.000 description 1
• ZDOLXCKKXHSEJG-UHFFFAOYSA-N 2-but-3-enylisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC=C)C(=O)C2=C1 ZDOLXCKKXHSEJG-UHFFFAOYSA-N 0.000 description 1
• HHAPNPCLONTVTL-UHFFFAOYSA-N 2-chloro-7-(2,4-difluorophenyl)-n-[5-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]pentan-2-yl]-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C(Cl)=NC=2C(C=3C(=CC(F)=CC=3)F)CCC=2C=1NC(C)CCCOC1=CC([N+]([O-])=O)=CC=C1N1C=NC(C)=N1 HHAPNPCLONTVTL-UHFFFAOYSA-N 0.000 description 1
• FVAUDXXLLJKCRN-UHFFFAOYSA-N 2-chloro-n-[3-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]propyl]-7-(2,4-difluorophenyl)-n-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C(Cl)=NC=2C(C=3C(=CC(F)=CC=3)F)CCC=2C=1N(C)CCCOC1=CC([N+]([O-])=O)=CC=C1N1C=NC(Cl)=C1 FVAUDXXLLJKCRN-UHFFFAOYSA-N 0.000 description 1
• DUARJJIHEBWXCT-UHFFFAOYSA-N 2-chloro-n-[3-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]propyl]-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C=1C([N+](=O)[O-])=CC=C(N2C=C(Cl)N=C2)C=1OCCCNC(C=1CC2)=NC(Cl)=NC=1C2C1=CC=CC=C1 DUARJJIHEBWXCT-UHFFFAOYSA-N 0.000 description 1
• FZJISOQWVSHKAG-UHFFFAOYSA-N 2-chloro-n-methyl-n-[3-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]propyl]-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C(Cl)=NC=2C(C=3C=CC=CC=3)CCC=2C=1N(C)CCCOC1=CC([N+]([O-])=O)=CC=C1N1C=NC(C)=N1 FZJISOQWVSHKAG-UHFFFAOYSA-N 0.000 description 1
• OCVXSFKKWXMYPF-UHFFFAOYSA-N 2-chloroimidazole Chemical compound ClC1=NC=CN1 OCVXSFKKWXMYPF-UHFFFAOYSA-N 0.000 description 1
• UXBIHGQYRYAMFN-UHFFFAOYSA-N 2-fluoro-4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C(F)=C1 UXBIHGQYRYAMFN-UHFFFAOYSA-N 0.000 description 1
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
• QKTPDZFKDNXBIN-UHFFFAOYSA-N 3-[2-(4-chloroimidazol-1-yl)-5-nitrophenoxy]-n-methylpropan-1-amine Chemical compound CNCCCOC1=CC([N+]([O-])=O)=CC=C1N1C=C(Cl)N=C1 QKTPDZFKDNXBIN-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• GAWNBKUTBVLIPL-UHFFFAOYSA-N 3-fluoro-2-nitrophenol Chemical class OC1=CC=CC(F)=C1[N+]([O-])=O GAWNBKUTBVLIPL-UHFFFAOYSA-N 0.000 description 1
• MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
• BOAFCICMVMFLIT-UHFFFAOYSA-N 3-nitro-1h-pyridin-2-one Chemical class OC1=NC=CC=C1[N+]([O-])=O BOAFCICMVMFLIT-UHFFFAOYSA-N 0.000 description 1
• VBRMIWOLUCKNTN-UHFFFAOYSA-N 4-(triazol-1-yl)aniline Chemical class C1=CC(N)=CC=C1N1N=NC=C1 VBRMIWOLUCKNTN-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
• BVNXQDKSNVIWHI-UHFFFAOYSA-N 4-amino-2-[2-[2-[[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]ethyl-methylamino]ethoxy]benzonitrile Chemical compound C=1C(N)=CC=C(C#N)C=1OCCN(C)CCNC(C=1CC2)=NC(Cl)=NC=1C2C1=CC=C(F)C=C1 BVNXQDKSNVIWHI-UHFFFAOYSA-N 0.000 description 1
• GWGGXKKRQCLBIH-UHFFFAOYSA-N 4-amino-2-[3-[(2-chloro-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl)-methylamino]propoxy]benzonitrile Chemical compound N=1C(Cl)=NC=2C(C=3C=CC=CC=3)CCC=2C=1N(C)CCCOC1=CC(N)=CC=C1C#N GWGGXKKRQCLBIH-UHFFFAOYSA-N 0.000 description 1
• RAVRHMUXLSMTDF-UHFFFAOYSA-N 4-amino-2-[4-[(2-chloro-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl)amino]butoxy]benzonitrile Chemical compound NC1=CC=C(C#N)C(OCCCCNC=2C=3CCC(C=3N=C(Cl)N=2)C=2C=CC=CC=2)=C1 RAVRHMUXLSMTDF-UHFFFAOYSA-N 0.000 description 1
• QCSLESCNLXTKFB-UHFFFAOYSA-N 4-amino-2-[4-[[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]-2-hydroxybutoxy]benzonitrile Chemical compound NC1=CC=C(C#N)C(OCC(O)CCNC=2C=3CCC(C=3N=C(Cl)N=2)C=2C=CC(F)=CC=2)=C1 QCSLESCNLXTKFB-UHFFFAOYSA-N 0.000 description 1
• JAXJUENAJXWFBX-UHFFFAOYSA-N 4-aminopentan-1-ol Chemical compound CC(N)CCCO JAXJUENAJXWFBX-UHFFFAOYSA-N 0.000 description 1
• FMSFCCUJAMIDSU-UHFFFAOYSA-N 4-chloro-2,6-dimethoxy-5-prop-2-enylpyrimidine Chemical compound COC1=NC(Cl)=C(CC=C)C(OC)=N1 FMSFCCUJAMIDSU-UHFFFAOYSA-N 0.000 description 1
• JHNRTJRDRWKAIW-UHFFFAOYSA-N 4-chloro-2,6-dimethoxypyrimidine Chemical compound COC1=CC(Cl)=NC(OC)=N1 JHNRTJRDRWKAIW-UHFFFAOYSA-N 0.000 description 1
• GVSNQMFKEPBIOY-UHFFFAOYSA-N 4-methyl-2h-triazole Chemical compound CC=1C=NNN=1 GVSNQMFKEPBIOY-UHFFFAOYSA-N 0.000 description 1
• JPCDRPBITBIMLU-UHFFFAOYSA-N 4-n-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidine-2,4-diamine Chemical compound CNC1=NC(N)=NC2=C1CCC2 JPCDRPBITBIMLU-UHFFFAOYSA-N 0.000 description 1
• PZKFSRWSQOQYNR-UHFFFAOYSA-N 5-methyl-1h-1,2,4-triazole Chemical compound CC1=NC=NN1 PZKFSRWSQOQYNR-UHFFFAOYSA-N 0.000 description 1
• PUFRHYBLNBADIZ-UHFFFAOYSA-N 5-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine Chemical compound C1(=CC=CC=C1)C1CCC=2N=C(N=C(C21)N)N PUFRHYBLNBADIZ-UHFFFAOYSA-N 0.000 description 1
• RYMSIBOTNUIQAP-UHFFFAOYSA-N 6-(3-methyl-1,2,4-triazol-1-yl)-18-phenyl-8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1(20),3(22),4,6,14(21),15(19)-hexaene Chemical compound N1=C(C)N=CN1C1=CC=C(N2)C=C1OCCCCNC1=NC2=NC2=C1CCC2C1=CC=CC=C1 RYMSIBOTNUIQAP-UHFFFAOYSA-N 0.000 description 1
• RGBPEXFLCDGACP-UHFFFAOYSA-N 8-(4-fluorophenyl)-6-methyl-1,5,7,8-tetrahydropyrido[4,3-d]pyrimidine-2,4-dione Chemical compound C1=2NC(=O)NC(=O)C=2CN(C)CC1C1=CC=C(F)C=C1 RGBPEXFLCDGACP-UHFFFAOYSA-N 0.000 description 1
• JRWAWKIVAMGLJO-UHFFFAOYSA-N 8-oxa-2,12,19,20-tetrazatetracyclo[11.6.1.13,7.014,18]henicosa-1,3(21),4,6,9,11,13(20),14,16,18-decaene Chemical compound N1=C2C(C=3N=CC=COC=4C=CC=C(N=C1N=3)C=4)=CC=C2 JRWAWKIVAMGLJO-UHFFFAOYSA-N 0.000 description 1
• KEIIYOKPSKQJTB-UHFFFAOYSA-N 8-oxa-2,13,20,21-tetrazatetracyclo[12.6.1.13,7.015,19]docosa-1,3(22),4,6,10,12,14(21),15,17,19-decaene Chemical compound N1=C2C(C=3N=CC=CCOC=4C=CC=C(N=C1N=3)C=4)=CC=C2 KEIIYOKPSKQJTB-UHFFFAOYSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 206010002329 Aneurysm Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 101150041968 CDC13 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 208000002177 Cataract Diseases 0.000 description 1
• 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
• 208000028698 Cognitive impairment Diseases 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
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 206010012239 Delusion Diseases 0.000 description 1
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
• 241000551547 Dione <red algae> Species 0.000 description 1
• 101100224482 Drosophila melanogaster PolE1 gene Proteins 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
• 241000237858 Gastropoda Species 0.000 description 1
• 241000206672 Gelidium Species 0.000 description 1
• 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 1
• 239000007818 Grignard reagent Substances 0.000 description 1
• 206010019075 Hallucination, visual Diseases 0.000 description 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
• 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• 229920000715 Mucilage Polymers 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 102000008300 Mutant Proteins Human genes 0.000 description 1
• 108010021466 Mutant Proteins Proteins 0.000 description 1
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 208000027089 Parkinsonian disease Diseases 0.000 description 1
• 206010034010 Parkinsonism Diseases 0.000 description 1
• 101000579647 Penaeus vannamei Penaeidin-2a Proteins 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
• 229910019567 Re Re Inorganic materials 0.000 description 1
• 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
• 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 102100040347 TAR DNA-binding protein 43 Human genes 0.000 description 1
• 101710150875 TAR DNA-binding protein 43 Proteins 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 208000030886 Traumatic Brain injury Diseases 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
• 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
• 102000044159 Ubiquitin Human genes 0.000 description 1
• 108090000848 Ubiquitin Proteins 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• SLSGHPNWPPHNHN-UHFFFAOYSA-M [Br-].FC1=CC=C([Mg+])C(F)=C1 Chemical compound [Br-].FC1=CC=C([Mg+])C(F)=C1 SLSGHPNWPPHNHN-UHFFFAOYSA-M 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 229940091181 aconitic acid Drugs 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 230000032683 aging Effects 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 125000003418 alkyl amino alkoxy group Chemical group 0.000 description 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 125000005336 allyloxy group Chemical group 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 206010002022 amyloidosis Diseases 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 101150089041 aph-1 gene Proteins 0.000 description 1
• 201000007201 aphasia Diseases 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000008122 artificial sweetener Substances 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 238000006254 arylation reaction Methods 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 238000011888 autopsy Methods 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 150000008359 benzonitriles Chemical class 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 238000010170 biological method Methods 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• SKKTUOZKZKCGTB-UHFFFAOYSA-N butyl carbamate Chemical compound CCCCOC(N)=O SKKTUOZKZKCGTB-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 230000021523 carboxylation Effects 0.000 description 1
• 238000006473 carboxylation reaction Methods 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 201000011529 cardiovascular cancer Diseases 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• GTZCVFVGUGFEME-IWQZZHSRSA-N cis-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C\C(O)=O GTZCVFVGUGFEME-IWQZZHSRSA-N 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 150000001879 copper Chemical class 0.000 description 1
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 231100000868 delusion Toxicity 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000008021 deposition Effects 0.000 description 1
• 125000004984 dialkylaminoalkoxy group Chemical group 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• YZIJMEOFJVECDM-UHFFFAOYSA-N ethyl 2-cyano-2-(4-fluorophenyl)acetate Chemical compound CCOC(=O)C(C#N)C1=CC=C(F)C=C1 YZIJMEOFJVECDM-UHFFFAOYSA-N 0.000 description 1
• LRSQKGAKYUHQNQ-UHFFFAOYSA-N ethyl 2-oxo-3-phenylcyclopentane-1-carboxylate Chemical compound O=C1C(C(=O)OCC)CCC1C1=CC=CC=C1 LRSQKGAKYUHQNQ-UHFFFAOYSA-N 0.000 description 1
• UOPRKTKOSIUNSP-UHFFFAOYSA-N ethyl 3-[(3-ethoxy-3-oxopropyl)-[(4-methoxyphenyl)methyl]amino]-2-(4-fluorophenyl)propanoate Chemical compound C=1C=C(OC)C=CC=1CN(CCC(=O)OCC)CC(C(=O)OCC)C1=CC=C(F)C=C1 UOPRKTKOSIUNSP-UHFFFAOYSA-N 0.000 description 1
• ZWQJIPBVYNPNIG-UHFFFAOYSA-N ethyl 3-[(3-ethoxy-3-oxopropyl)-methylamino]-2-phenylpropanoate Chemical compound CCOC(=O)CCN(C)CC(C(=O)OCC)C1=CC=CC=C1 ZWQJIPBVYNPNIG-UHFFFAOYSA-N 0.000 description 1
• XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
• MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000010419 fine particle Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 229960002598 fumaric acid Drugs 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 239000003540 gamma secretase inhibitor Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical class OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 239000008309 hydrophilic cream Substances 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 239000012216 imaging agent Substances 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000007937 lozenge Substances 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
• BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229940098895 maleic acid Drugs 0.000 description 1
• 150000002690 malonic acid derivatives Chemical class 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
• IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• SDDKIZNHOCEXTF-UHFFFAOYSA-N methyl carbamimidothioate Chemical compound CSC(N)=N SDDKIZNHOCEXTF-UHFFFAOYSA-N 0.000 description 1
• 125000005911 methyl carbonate group Chemical class 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 230000007659 motor function Effects 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 230000023105 myelination Effects 0.000 description 1
• KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 1
• ZBKPIXXPVRGMKN-UHFFFAOYSA-N n-[2-[2-[5-amino-2-(4-chloroimidazol-1-yl)phenoxy]ethoxy]ethyl]-2-chloro-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C=1C(N)=CC=C(N2C=C(Cl)N=C2)C=1OCCOCCNC(C=1CC2)=NC(Cl)=NC=1C2C1=CC=CC=C1 ZBKPIXXPVRGMKN-UHFFFAOYSA-N 0.000 description 1
• XOPKOHKWASKCSF-UHFFFAOYSA-N n-[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-n'-methyl-n'-[2-[2-(3-methyl-1,2,4-triazol-1-yl)-5-nitrophenoxy]ethyl]ethane-1,2-diamine Chemical compound C=1C([N+]([O-])=O)=CC=C(N2N=C(C)N=C2)C=1OCCN(C)CCNC(C=1CC2)=NC(Cl)=NC=1C2C1=CC=C(F)C=C1 XOPKOHKWASKCSF-UHFFFAOYSA-N 0.000 description 1
• VZUGBLTVBZJZOE-KRWDZBQOSA-N n-[3-[(4s)-2-amino-1,4-dimethyl-6-oxo-5h-pyrimidin-4-yl]phenyl]-5-chloropyrimidine-2-carboxamide Chemical compound N1=C(N)N(C)C(=O)C[C@@]1(C)C1=CC=CC(NC(=O)C=2N=CC(Cl)=CN=2)=C1 VZUGBLTVBZJZOE-KRWDZBQOSA-N 0.000 description 1
• UCUZUPDBSKPEJQ-UHFFFAOYSA-N n-[3-[5-amino-2-(3-methyl-1,2,4-triazol-1-yl)phenoxy]propyl]-2-chloro-7-(2,4-difluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N1=C(C)N=CN1C1=CC=C(N)C=C1OCCCNC1=NC(Cl)=NC2=C1CCC2C1=CC=C(F)C=C1F UCUZUPDBSKPEJQ-UHFFFAOYSA-N 0.000 description 1
• HRSHFXMKLUBIGA-UHFFFAOYSA-N n-[3-[5-amino-2-(3-methyl-1,2,4-triazol-1-yl)phenoxy]propyl]-2-chloro-n-methyl-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C(Cl)=NC=2C(C=3C=CC=CC=3)CCC=2C=1N(C)CCCOC1=CC(N)=CC=C1N1C=NC(C)=N1 HRSHFXMKLUBIGA-UHFFFAOYSA-N 0.000 description 1
• COEVTWLLSHIYTF-UHFFFAOYSA-N n-[3-[5-amino-2-(4-chloroimidazol-1-yl)phenoxy]propyl]-2-chloro-7-(2,4-difluorophenyl)-n-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C(Cl)=NC=2C(C=3C(=CC(F)=CC=3)F)CCC=2C=1N(C)CCCOC1=CC(N)=CC=C1N1C=NC(Cl)=C1 COEVTWLLSHIYTF-UHFFFAOYSA-N 0.000 description 1
• LGTGKWJFNMLCAM-UHFFFAOYSA-N n-[3-[5-amino-2-(4-chloroimidazol-1-yl)phenoxy]propyl]-2-chloro-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C=1C(N)=CC=C(N2C=C(Cl)N=C2)C=1OCCCNC(C=1CC2)=NC(Cl)=NC=1C2C1=CC=CC=C1 LGTGKWJFNMLCAM-UHFFFAOYSA-N 0.000 description 1
• OUOVQXHKQGTVML-UHFFFAOYSA-N n-[3-[5-amino-2-(4-chloroimidazol-1-yl)phenoxy]propyl]-2-chloro-n-methyl-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C(Cl)=NC=2C(C=3C=CC=CC=3)CCC=2C=1N(C)CCCOC1=CC(N)=CC=C1N1C=NC(Cl)=C1 OUOVQXHKQGTVML-UHFFFAOYSA-N 0.000 description 1
• WZQUZRLLQSGEAE-UHFFFAOYSA-N n-[4-[5-amino-2-(3-methyl-1,2,4-triazol-1-yl)phenoxy]butyl]-2-chloro-8-(4-fluorophenyl)-6-methyl-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C12=NC(Cl)=NC(NCCCCOC=3C(=CC=C(N)C=3)N3N=C(C)N=C3)=C2CN(C)CC1C1=CC=C(F)C=C1 WZQUZRLLQSGEAE-UHFFFAOYSA-N 0.000 description 1
• YRSNATRWTBJOPY-UHFFFAOYSA-N n-but-3-enyl-2-chloro-n-methyl-7-phenyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1CC=2C(N(CCC=C)C)=NC(Cl)=NC=2C1C1=CC=CC=C1 YRSNATRWTBJOPY-UHFFFAOYSA-N 0.000 description 1
• FWNDUPRDKCMSGG-UHFFFAOYSA-N n-methylbut-1-en-1-amine Chemical compound CCC=CNC FWNDUPRDKCMSGG-UHFFFAOYSA-N 0.000 description 1
• 239000007923 nasal drop Substances 0.000 description 1
• 229940100662 nasal drops Drugs 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 235000021096 natural sweeteners Nutrition 0.000 description 1
• 229910052754 neon Inorganic materials 0.000 description 1
• GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
• 231100000189 neurotoxic Toxicity 0.000 description 1
• 230000002887 neurotoxic effect Effects 0.000 description 1
• 102000046701 nicastrin Human genes 0.000 description 1
• 108700022821 nicastrin Proteins 0.000 description 1
• RBXVOQPAMPBADW-UHFFFAOYSA-N nitrous acid;phenol Chemical class ON=O.OC1=CC=CC=C1 RBXVOQPAMPBADW-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002902 organometallic compounds Chemical class 0.000 description 1
• 229910052762 osmium Inorganic materials 0.000 description 1
• SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 238000012261 overproduction Methods 0.000 description 1
• PLQCPDHNBLXOEO-UHFFFAOYSA-N oxazine-3,4-dione Chemical class O=C1C=CONC1=O PLQCPDHNBLXOEO-UHFFFAOYSA-N 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000011236 particulate material Substances 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 230000008506 pathogenesis 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
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
• 235000019477 peppermint oil Nutrition 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000000865 phosphorylative effect Effects 0.000 description 1
• 125000005547 pivalate group Chemical group 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 229920002721 polycyanoacrylate Polymers 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 229920006324 polyoxymethylene Polymers 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 238000003825 pressing Methods 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011253 protective coating Substances 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 150000008512 pyrimidinediones Chemical class 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• HBFNEQHBPPNHEG-UHFFFAOYSA-N tert-butyl n-[2-(5-amino-2-cyanophenoxy)ethyl]-n-[2-[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]ethyl]carbamate Chemical compound N=1C(Cl)=NC=2C(C=3C=CC(F)=CC=3)CCC=2C=1CCN(C(=O)OC(C)(C)C)CCOC1=CC(N)=CC=C1C#N HBFNEQHBPPNHEG-UHFFFAOYSA-N 0.000 description 1
• YKQXIFSTCRISJB-UHFFFAOYSA-N tert-butyl n-[2-[2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]ethyl]-n-[2-(2-cyano-5-nitrophenoxy)ethyl]carbamate Chemical compound N=1C(Cl)=NC=2C(C=3C=CC(F)=CC=3)CCC=2C=1CCN(C(=O)OC(C)(C)C)CCOC1=CC([N+]([O-])=O)=CC=C1C#N YKQXIFSTCRISJB-UHFFFAOYSA-N 0.000 description 1
• PGDKJORLTNEJES-UHFFFAOYSA-N tert-butyl n-[3-(2-cyano-5-nitrophenoxy)propyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CCCOC1=CC([N+]([O-])=O)=CC=C1C#N PGDKJORLTNEJES-UHFFFAOYSA-N 0.000 description 1
• QUCDGQORXKIITC-UHFFFAOYSA-N tert-butyl n-[4-(2-cyano-5-nitrophenoxy)butyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCCOC1=CC([N+]([O-])=O)=CC=C1C#N QUCDGQORXKIITC-UHFFFAOYSA-N 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 229940100611 topical cream Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229940100615 topical ointment Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 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
• 108091005703 transmembrane proteins Proteins 0.000 description 1
• 102000035160 transmembrane proteins Human genes 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 229930195724 β-lactose Natural products 0.000 description 1
• PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1