PT1492785E - Derivados de 2-hidroxi-3-heteroarilindole como inibidores de gsk3 - Google Patents

Info

Publication number

PT1492785E

PT1492785E PT03745498T PT03745498T PT1492785E PT 1492785 E PT1492785 E PT 1492785E PT 03745498 T PT03745498 T PT 03745498T PT 03745498 T PT03745498 T PT 03745498T PT 1492785 E PT1492785 E PT 1492785E

Authority

PT

Portugal

Prior art keywords

pyridin

hydroxy

indol

hydrochloride

indole

Prior art date

2002-03-28

Links

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• 239000003112 inhibitor Substances 0.000 title description 6
• 101100176788 Dictyostelium discoideum gskA gene Proteins 0.000 title 1
• 101100149391 Drosophila melanogaster sgg gene Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 242
• 239000002904 solvent Substances 0.000 claims description 98
• -1 NR 16 R 17 Chemical group 0.000 claims description 80
• 239000002585 base Substances 0.000 claims description 78
• 238000006243 chemical reaction Methods 0.000 claims description 72
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 65
• 150000003839 salts Chemical class 0.000 claims description 30
• 229910052736 halogen Inorganic materials 0.000 claims description 24
• 150000002367 halogens Chemical class 0.000 claims description 24
• 238000000034 method Methods 0.000 claims description 23
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
• 125000000217 alkyl group Chemical group 0.000 claims description 20
• 238000010992 reflux Methods 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 229910052717 sulfur Inorganic materials 0.000 claims description 19
• 206010012289 Dementia Diseases 0.000 claims description 18
• 239000012458 free base Substances 0.000 claims description 18
• 125000005843 halogen group Chemical group 0.000 claims description 18
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 17
• 150000001412 amines Chemical class 0.000 claims description 17
• 239000003153 chemical reaction reagent Substances 0.000 claims description 17
• 125000005842 heteroatom Chemical group 0.000 claims description 17
• 208000024827 Alzheimer disease Diseases 0.000 claims description 16
• 239000000460 chlorine Substances 0.000 claims description 15
• 125000000623 heterocyclic group Chemical group 0.000 claims description 15
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 208000010877 cognitive disease Diseases 0.000 claims description 13
• 230000008569 process Effects 0.000 claims description 13
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
• 229910052794 bromium Inorganic materials 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 12
• 239000011737 fluorine Substances 0.000 claims description 12
• 229910052731 fluorine Inorganic materials 0.000 claims description 12
• 239000001257 hydrogen Substances 0.000 claims description 12
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 11
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
• 238000002360 preparation method Methods 0.000 claims description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 230000002265 prevention Effects 0.000 claims description 8
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
• 201000010099 disease Diseases 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
• 201000004384 Alopecia Diseases 0.000 claims description 6
• 208000020925 Bipolar disease Diseases 0.000 claims description 6
• 150000001204 N-oxides Chemical class 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 201000000980 schizophrenia Diseases 0.000 claims description 6
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 5
• 230000006999 cognitive decline Effects 0.000 claims description 5
• 230000004770 neurodegeneration Effects 0.000 claims description 5
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
• BLTVBQXJFVRPFK-UHFFFAOYSA-N AZD1080 Chemical compound OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 BLTVBQXJFVRPFK-UHFFFAOYSA-N 0.000 claims description 4
• VZDDMDDGEIAVJR-UHFFFAOYSA-N OC=1NC2=CC=C(C=3SC=CC=3)C=C2C=1C([N+](=C1)[O-])=CC=C1CN1CCOCC1 Chemical compound OC=1NC2=CC=C(C=3SC=CC=3)C=C2C=1C([N+](=C1)[O-])=CC=C1CN1CCOCC1 VZDDMDDGEIAVJR-UHFFFAOYSA-N 0.000 claims description 4
• 208000018737 Parkinson disease Diseases 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 4
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 231100000876 cognitive deterioration Toxicity 0.000 claims description 4
• 230000006866 deterioration Effects 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• ZSBINQQBBOUXFI-UHFFFAOYSA-N ethyl 6-(2-hydroxy-5-nitro-1H-indol-3-yl)pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OCC)=CC=C1C1=C(O)NC2=CC=C([N+]([O-])=O)C=C12 ZSBINQQBBOUXFI-UHFFFAOYSA-N 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 230000003676 hair loss Effects 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• ZFRDGCKDAKVMRW-WLHGVMLRSA-N (E)-but-2-enedioic acid [6-(2-hydroxy-5-nitro-1H-indol-3-yl)pyridin-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C)CCN1C(=O)c1ccc(-c2c([nH]c3ccc(cc32)[N+]([O-])=O)O)nc1 ZFRDGCKDAKVMRW-WLHGVMLRSA-N 0.000 claims description 3
• HGCLVHWOIGDXAZ-UHFFFAOYSA-N 2-hydroxy-3-(5-morpholin-4-ylsulfonylpyridin-2-yl)-1H-indole-5-carbonitrile Chemical compound OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1S(=O)(=O)N1CCOCC1 HGCLVHWOIGDXAZ-UHFFFAOYSA-N 0.000 claims description 3
• AGWBFQVRRSLCHJ-UHFFFAOYSA-N 2-hydroxy-3-[5-(4-methylpiperazine-1-carbonyl)pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 AGWBFQVRRSLCHJ-UHFFFAOYSA-N 0.000 claims description 3
• HSQKJKZGOSVCOZ-UHFFFAOYSA-N 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 HSQKJKZGOSVCOZ-UHFFFAOYSA-N 0.000 claims description 3
• GXJPJFUWGWGPBU-UHFFFAOYSA-N 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-6-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC(C#N)=CC=C2C=1C(N=C1)=CC=C1CN1CCOCC1 GXJPJFUWGWGPBU-UHFFFAOYSA-N 0.000 claims description 3
• FJVACSNRHIUTDK-UHFFFAOYSA-N 2-hydroxy-3-[5-(piperidin-1-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN1CCCCC1 FJVACSNRHIUTDK-UHFFFAOYSA-N 0.000 claims description 3
• GPTISHQYMJHWON-UHFFFAOYSA-N 2-hydroxy-3-[5-[(4-methylpiperidin-1-yl)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound C1CC(C)CCN1CC1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 GPTISHQYMJHWON-UHFFFAOYSA-N 0.000 claims description 3
• KPMVLWSSNOTENQ-UHFFFAOYSA-N 2-hydroxy-3-[5-[(4-phenylpiperazin-1-yl)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN(CC1)CCN1C1=CC=CC=C1 KPMVLWSSNOTENQ-UHFFFAOYSA-N 0.000 claims description 3
• XYQALSFZTTXKKD-UHFFFAOYSA-N 2-hydroxy-3-[5-[(4-pyrrolidin-1-ylpiperidin-1-yl)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN(CC1)CCC1N1CCCC1 XYQALSFZTTXKKD-UHFFFAOYSA-N 0.000 claims description 3
• LQNNIYIDKIZEQU-UHFFFAOYSA-N 2-hydroxy-3-[5-[(N-methylanilino)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound C=1C=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=CC=1CN(C)C1=CC=CC=C1 LQNNIYIDKIZEQU-UHFFFAOYSA-N 0.000 claims description 3
• CFBOLIJNHXMZMR-UHFFFAOYSA-N 2-hydroxy-3-[5-[4-(3-methylbutyl)piperazin-1-yl]sulfonylpyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.C1CN(CCC(C)C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 CFBOLIJNHXMZMR-UHFFFAOYSA-N 0.000 claims description 3
• BGAFIJLLIWATJM-UHFFFAOYSA-N 2-hydroxy-3-[5-[[4-[2-nitro-4-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN(CC1)CCN1C1=CC=C(C(F)(F)F)C=C1[N+]([O-])=O BGAFIJLLIWATJM-UHFFFAOYSA-N 0.000 claims description 3
• CCRQRQITUSYUCY-UHFFFAOYSA-N 3-[3-bromo-5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-5-nitro-1H-indol-2-ol hydrochloride Chemical compound Cl.C1CN(C)CCN1S(=O)(=O)C(C=C1Br)=CN=C1C1=C(O)NC2=CC=C([N+]([O-])=O)C=C12 CCRQRQITUSYUCY-UHFFFAOYSA-N 0.000 claims description 3
• QPPWLYQVGNXFTA-UHFFFAOYSA-N 3-[5-(4-benzylpiperazin-1-yl)sulfonylpyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1S(=O)(=O)N(CC1)CCN1CC1=CC=CC=C1 QPPWLYQVGNXFTA-UHFFFAOYSA-N 0.000 claims description 3
• OTFZDRAEWUHKJF-UHFFFAOYSA-N 3-[5-(4-ethylpiperazin-1-yl)sulfonylpyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.C1CN(CC)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 OTFZDRAEWUHKJF-UHFFFAOYSA-N 0.000 claims description 3
• PSGREWNLJTVWIU-UHFFFAOYSA-N 3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-indol-2-ol hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C(F)(F)F)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 PSGREWNLJTVWIU-UHFFFAOYSA-N 0.000 claims description 3
• BZSXDPUXOKMIHP-UHFFFAOYSA-N 3-[5-[[2-cyanoethyl(ethyl)amino]methyl]pyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile Chemical compound N1=CC(CN(CCC#N)CC)=CC=C1C1=C(O)NC2=CC=C(C#N)C=C12 BZSXDPUXOKMIHP-UHFFFAOYSA-N 0.000 claims description 3
• NYLFEHCKPMZKQY-UHFFFAOYSA-N 3-[5-[[3-(dimethylamino)pyrrolidin-1-yl]methyl]pyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile Chemical compound C1C(N(C)C)CCN1CC1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 NYLFEHCKPMZKQY-UHFFFAOYSA-N 0.000 claims description 3
• VOHSMAUFLUYXRP-UHFFFAOYSA-N 3-[5-[[cyclohexyl(methyl)amino]methyl]pyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile Chemical compound C=1C=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=CC=1CN(C)C1CCCCC1 VOHSMAUFLUYXRP-UHFFFAOYSA-N 0.000 claims description 3
• XVKCQXSZBLDOFH-UHFFFAOYSA-N 3-[5-[[furan-2-ylmethyl(methyl)amino]methyl]pyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile Chemical compound C=1C=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=CC=1CN(C)CC1=CC=CO1 XVKCQXSZBLDOFH-UHFFFAOYSA-N 0.000 claims description 3
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 3
• QBMKVGAHJVUDMD-UHFFFAOYSA-N 5,6-dibromo-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol hydrochloride Chemical compound Cl.OC=1NC2=CC(Br)=C(Br)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 QBMKVGAHJVUDMD-UHFFFAOYSA-N 0.000 claims description 3
• FAABSFPFSLKXNZ-UHFFFAOYSA-N 5-(furan-2-yl)-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C=3OC=CC=3)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 FAABSFPFSLKXNZ-UHFFFAOYSA-N 0.000 claims description 3
• IJLCISXHAWDSQV-UHFFFAOYSA-N 5-bromo-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol hydrochloride Chemical compound Cl.OC=1NC2=CC=C(Br)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 IJLCISXHAWDSQV-UHFFFAOYSA-N 0.000 claims description 3
• LLAZTZBIMDHGFQ-UHFFFAOYSA-N 6-(5-cyano-2-hydroxy-1H-indol-3-yl)-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1S(=O)(=O)NCCN1CCCC1 LLAZTZBIMDHGFQ-UHFFFAOYSA-N 0.000 claims description 3
• GECIALRGJBQECL-UHFFFAOYSA-N 6-(5-cyano-2-hydroxy-1H-indol-3-yl)-N-methyl-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide hydrochloride Chemical compound Cl.C=1C=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=CC=1S(=O)(=O)N(C)CCN1CCCC1 GECIALRGJBQECL-UHFFFAOYSA-N 0.000 claims description 3
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 3
• 201000010374 Down Syndrome Diseases 0.000 claims description 3
• 208000023105 Huntington disease Diseases 0.000 claims description 3
• 208000019022 Mood disease Diseases 0.000 claims description 3
• 208000014060 Niemann-Pick disease Diseases 0.000 claims description 3
• KNAGMHCIILIDOU-UHFFFAOYSA-N OC=1NC2=CC=C(C=3C=NC=CC=3)C=C2C=1C([N+](=C1)[O-])=CC=C1CN1CCOCC1 Chemical compound OC=1NC2=CC=C(C=3C=NC=CC=3)C=C2C=1C([N+](=C1)[O-])=CC=C1CN1CCOCC1 KNAGMHCIILIDOU-UHFFFAOYSA-N 0.000 claims description 3
• GFIQRWDEXWMTCS-UHFFFAOYSA-N OC=1NC2=CC=C(C=3OC=CC=3)C=C2C=1C([N+](=C1)[O-])=CC=C1CN1CCOCC1 Chemical compound OC=1NC2=CC=C(C=3OC=CC=3)C=C2C=1C([N+](=C1)[O-])=CC=C1CN1CCOCC1 GFIQRWDEXWMTCS-UHFFFAOYSA-N 0.000 claims description 3
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 3
• 208000036757 Postencephalitic parkinsonism Diseases 0.000 claims description 3
• 206010044688 Trisomy 21 Diseases 0.000 claims description 3
• PCEVLYRCZVWKNL-UHFFFAOYSA-N [6-(2-hydroxy-5-nitro-1H-indol-3-yl)pyridin-3-yl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone hydrochloride Chemical compound Cl.OC=1NC2=CC=C([N+]([O-])=O)C=C2C=1C(N=C1)=CC=C1C(=O)N(CC1)CCC1N1CCCC1 PCEVLYRCZVWKNL-UHFFFAOYSA-N 0.000 claims description 3
• QVPHTKOEMVVGNO-UHFFFAOYSA-N [6-(2-hydroxy-5-nitro-1H-indol-3-yl)pyridin-3-yl]-morpholin-4-ylmethanone Chemical compound OC=1NC2=CC=C([N+]([O-])=O)C=C2C=1C(N=C1)=CC=C1C(=O)N1CCOCC1 QVPHTKOEMVVGNO-UHFFFAOYSA-N 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 239000003433 contraceptive agent Substances 0.000 claims description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
• 208000024963 hair loss Diseases 0.000 claims description 3
• 208000000170 postencephalitic Parkinson disease Diseases 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• APRYBBRXBYNGRD-WLHGVMLRSA-N (E)-but-2-enedioic acid 3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-5-(1,3-thiazol-4-yl)-1H-indol-2-ol Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C)CCN1S(=O)(=O)c1ccc(-c2c([nH]c3ccc(cc32)-c2cscn2)O)nc1 APRYBBRXBYNGRD-WLHGVMLRSA-N 0.000 claims description 2
• TUHYCRZRVGKOJC-UHFFFAOYSA-N 2-hydroxy-3-[4-(4-methylpiperazine-1-carbonyl)pyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C1=CC=NC(C=2C3=CC(=CC=C3NC=2O)C#N)=C1 TUHYCRZRVGKOJC-UHFFFAOYSA-N 0.000 claims description 2
• OZZYJFSOFDTEHW-UHFFFAOYSA-N 2-hydroxy-3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-6-carbonitrile hydrochloride Chemical compound Cl.C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC=C(C=C3NC=2O)C#N)N=C1 OZZYJFSOFDTEHW-UHFFFAOYSA-N 0.000 claims description 2
• GBLNSBPFSFVPQU-UHFFFAOYSA-N 2-hydroxy-3-[5-(pyrrolidin-1-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN1CCCC1 GBLNSBPFSFVPQU-UHFFFAOYSA-N 0.000 claims description 2
• PNSRYCSDXDXFBB-UHFFFAOYSA-N 2-hydroxy-3-[5-[(3-methylpiperidin-1-yl)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound C1C(C)CCCN1CC1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 PNSRYCSDXDXFBB-UHFFFAOYSA-N 0.000 claims description 2
• VBOGGFCZFUJSMT-UHFFFAOYSA-N 2-hydroxy-3-[5-[(4-methyl-1,4-diazepan-1-yl)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.C1CN(C)CCCN1CC1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 VBOGGFCZFUJSMT-UHFFFAOYSA-N 0.000 claims description 2
• AUBFRFKDPRVUMI-UHFFFAOYSA-N 3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indol-2-ol hydrochloride Chemical compound Cl.C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC=CC=C3NC=2O)N=C1 AUBFRFKDPRVUMI-UHFFFAOYSA-N 0.000 claims description 2
• RWYGDLZHZRWAGT-UHFFFAOYSA-N 3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-5-(1,3-oxazol-5-yl)-1H-indol-2-ol Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C=2OC=NC=2)N=C1 RWYGDLZHZRWAGT-UHFFFAOYSA-N 0.000 claims description 2
• LCXBCMKWUPCGNT-UHFFFAOYSA-N 3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-5-thiophen-2-yl-1H-indol-2-ol hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C=3SC=CC=3)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 LCXBCMKWUPCGNT-UHFFFAOYSA-N 0.000 claims description 2
• VJUKIBVGYYABIY-UHFFFAOYSA-N 3-[5-[[(4-chlorophenyl)methyl-methylamino]methyl]pyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile Chemical compound C=1C=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=CC=1CN(C)CC1=CC=C(Cl)C=C1 VJUKIBVGYYABIY-UHFFFAOYSA-N 0.000 claims description 2
• ISCKFWGPRHZHEU-UHFFFAOYSA-N 6-bromo-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol hydrochloride Chemical compound Cl.OC=1NC2=CC(Br)=CC=C2C=1C(N=C1)=CC=C1CN1CCOCC1 ISCKFWGPRHZHEU-UHFFFAOYSA-N 0.000 claims description 2
• 208000000044 Amnesia Diseases 0.000 claims description 2
• 201000002832 Lewy body dementia Diseases 0.000 claims description 2
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