CA2538381A1 - 3-heterocyclyl-indole derivatives as inhibitors of glycogen synthase kinase-3 (gsk-3) - Google Patents

Info

Publication number

CA2538381A1

CA2538381A1 CA002538381A CA2538381A CA2538381A1 CA 2538381 A1 CA2538381 A1 CA 2538381A1 CA 002538381 A CA002538381 A CA 002538381A CA 2538381 A CA2538381 A CA 2538381A CA 2538381 A1 CA2538381 A1 CA 2538381A1

Authority

CA

Canada

Prior art keywords

hydroxy

pyridin

indole

sulfonyl

carboxamide

Prior art date

2003-09-24

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 title claims description 50
• 102000001267 GSK3 Human genes 0.000 title claims 4
• 239000003112 inhibitor Substances 0.000 title description 6
• 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
• 101150090422 gsk-3 gene Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 288
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 50
• 150000003839 salts Chemical class 0.000 claims abstract description 41
• 238000000034 method Methods 0.000 claims abstract description 37
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
• 239000001257 hydrogen Substances 0.000 claims abstract description 33
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 29
• 230000008569 process Effects 0.000 claims abstract description 25
• 238000002360 preparation method Methods 0.000 claims abstract description 22
• 239000012458 free base Substances 0.000 claims abstract description 21
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 20
• 150000002367 halogens Chemical class 0.000 claims abstract description 20
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 9
• 239000000543 intermediate Substances 0.000 claims abstract description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 4
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 31
• -1 N-(2-Cyanoethyl)-2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-carboxamide hydrochloride Chemical compound 0.000 claims description 123
• 239000002585 base Substances 0.000 claims description 113
• 238000006243 chemical reaction Methods 0.000 claims description 104
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 103
• 239000002904 solvent Substances 0.000 claims description 97
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 74
• 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 54
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 47
• 150000001412 amines Chemical class 0.000 claims description 34
• 230000002265 prevention Effects 0.000 claims description 30
• 239000003153 chemical reaction reagent Substances 0.000 claims description 28
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 21
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 20
• 239000002253 acid Substances 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 17
• 150000002431 hydrogen Chemical class 0.000 claims description 17
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 206010012289 Dementia Diseases 0.000 claims description 13
• 208000010877 cognitive disease Diseases 0.000 claims description 13
• 238000010992 reflux Methods 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 11
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 9
• 241000124008 Mammalia Species 0.000 claims description 9
• 230000004913 activation Effects 0.000 claims description 9
• 150000003973 alkyl amines Chemical class 0.000 claims description 9
• 206010027175 memory impairment Diseases 0.000 claims description 9
• HWYXWVWNJLATGW-UHFFFAOYSA-N methyl 2-hydroxy-3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-5-carboxylate Chemical compound C12=CC(C(=O)OC)=CC=C2NC(O)=C1C(N=C1)=CC=C1S(=O)(=O)N1CCN(C)CC1 HWYXWVWNJLATGW-UHFFFAOYSA-N 0.000 claims description 9
• 201000004384 Alopecia Diseases 0.000 claims description 8
• 208000024827 Alzheimer disease Diseases 0.000 claims description 8
• 208000020925 Bipolar disease Diseases 0.000 claims description 8
• 201000010099 disease Diseases 0.000 claims description 8
• 208000035475 disorder Diseases 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• XRZSTVZROYQDLJ-UHFFFAOYSA-N 4-[(6-chloro-1-oxidopyridin-1-ium-3-yl)methyl]morpholine Chemical compound C1=C(Cl)[N+]([O-])=CC(CN2CCOCC2)=C1 XRZSTVZROYQDLJ-UHFFFAOYSA-N 0.000 claims description 7
• 230000009435 amidation Effects 0.000 claims description 7
• 238000007112 amidation reaction Methods 0.000 claims description 7
• 230000006870 function Effects 0.000 claims description 7
• BOOSOOHQWGDDJG-UHFFFAOYSA-N methyl 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxylate Chemical compound C12=CC(C(=O)OC)=CC=C2NC(O)=C1C(N=C1)=CC=C1CN1CCOCC1 BOOSOOHQWGDDJG-UHFFFAOYSA-N 0.000 claims description 7
• KMACAJJEVKEGCQ-UHFFFAOYSA-N methyl 3-[5-(diethylaminomethyl)pyridin-2-yl]-2-hydroxy-1H-indole-5-carboxylate Chemical compound N1=CC(CN(CC)CC)=CC=C1C1=C(O)NC2=CC=C(C(=O)OC)C=C12 KMACAJJEVKEGCQ-UHFFFAOYSA-N 0.000 claims description 7
• 201000000980 schizophrenia Diseases 0.000 claims description 7
• 206010012601 diabetes mellitus Diseases 0.000 claims description 6
• AJFUNKWEQCVOKI-UHFFFAOYSA-N n-(2-methoxyethyl)-2-oxo-1,3-dihydroindole-5-carboxamide Chemical compound COCCNC(=O)C1=CC=C2NC(=O)CC2=C1 AJFUNKWEQCVOKI-UHFFFAOYSA-N 0.000 claims description 6
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
• GDZNKWOYWRIHHC-UHFFFAOYSA-N 2-chloro-1-oxido-5-(piperidin-1-ylmethyl)pyridin-1-ium Chemical compound C1=C(Cl)[N+]([O-])=CC(CN2CCCCC2)=C1 GDZNKWOYWRIHHC-UHFFFAOYSA-N 0.000 claims description 5
• 206010019196 Head injury Diseases 0.000 claims description 5
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 5
• 206010034010 Parkinsonism Diseases 0.000 claims description 5
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 230000008878 coupling Effects 0.000 claims description 5
• 238000010168 coupling process Methods 0.000 claims description 5
• 238000005859 coupling reaction Methods 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 230000003676 hair loss Effects 0.000 claims description 5
• 230000026030 halogenation Effects 0.000 claims description 5
• 238000005658 halogenation reaction Methods 0.000 claims description 5
• JGHOWLLTSGGZJT-UHFFFAOYSA-N methyl 2-hydroxy-3-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]-1H-indole-5-carboxylate Chemical compound C12=CC(C(=O)OC)=CC=C2NC(O)=C1C(N=C1)=CC=C1CN1CCN(C)CC1 JGHOWLLTSGGZJT-UHFFFAOYSA-N 0.000 claims description 5
• 230000004770 neurodegeneration Effects 0.000 claims description 5
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
• DYRLZFVNXVAEDL-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)sulfonyl-4-(2-methoxyethyl)piperazine Chemical compound C1CN(CCOC)CCN1S(=O)(=O)C1=CC=C(Cl)N=C1 DYRLZFVNXVAEDL-UHFFFAOYSA-N 0.000 claims description 4
• MIFWNNROFUVTRK-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)sulfonyl-4-(2-pyrrolidin-1-ylethyl)piperazine Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)N1CCN(CCN2CCCC2)CC1 MIFWNNROFUVTRK-UHFFFAOYSA-N 0.000 claims description 4
• CCMXJHRETXCHTO-UHFFFAOYSA-N 1-[(6-chloro-1-oxidopyridin-1-ium-3-yl)methyl]-4-methylpiperazine Chemical compound C1CN(C)CCN1CC1=CC=C(Cl)[N+]([O-])=C1 CCMXJHRETXCHTO-UHFFFAOYSA-N 0.000 claims description 4
• ODWXXJVCDVLFHO-UHFFFAOYSA-N 2-[4-(6-chloropyridin-3-yl)sulfonylpiperazin-1-yl]-n,n-dimethylethanamine Chemical compound C1CN(CCN(C)C)CCN1S(=O)(=O)C1=CC=C(Cl)N=C1 ODWXXJVCDVLFHO-UHFFFAOYSA-N 0.000 claims description 4
• JJAHGJDXTZIKLJ-UHFFFAOYSA-N 2-hydroxy-3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 JJAHGJDXTZIKLJ-UHFFFAOYSA-N 0.000 claims description 4
• HFLLBRVZKPPKCH-UHFFFAOYSA-N 2-hydroxy-3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-5-carboxylic acid hydrochloride Chemical compound Cl.C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C(O)=O)N=C1 HFLLBRVZKPPKCH-UHFFFAOYSA-N 0.000 claims description 4
• PDWUYBUKLNGRBU-UHFFFAOYSA-N 2-oxo-n-(pyridin-2-ylmethyl)-1,3-dihydroindole-5-carboxamide Chemical compound C=1C=C2NC(=O)CC2=CC=1C(=O)NCC1=CC=CC=N1 PDWUYBUKLNGRBU-UHFFFAOYSA-N 0.000 claims description 4
• BHGFDIYEFUUCNM-UHFFFAOYSA-N 4-(6-chloropyridin-3-yl)sulfonylmorpholine Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)N1CCOCC1 BHGFDIYEFUUCNM-UHFFFAOYSA-N 0.000 claims description 4
• WVXOBZFHIVDDPU-UHFFFAOYSA-N 4-[(6-chloro-1-oxidopyridin-1-ium-3-yl)methyl]piperazin-2-one Chemical compound C1=C(Cl)[N+]([O-])=CC(CN2CC(=O)NCC2)=C1 WVXOBZFHIVDDPU-UHFFFAOYSA-N 0.000 claims description 4
• FFCUDEYUHMUZQB-UHFFFAOYSA-N 4-[2-(6-chloropyrimidin-4-yl)oxyethyl]morpholine Chemical compound C1=NC(Cl)=CC(OCCN2CCOCC2)=N1 FFCUDEYUHMUZQB-UHFFFAOYSA-N 0.000 claims description 4
• KTSVLYHMXKUEFX-UHFFFAOYSA-N 6-chloro-n-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)NCCN1CCCC1 KTSVLYHMXKUEFX-UHFFFAOYSA-N 0.000 claims description 4
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 4
• 201000010374 Down Syndrome Diseases 0.000 claims description 4
• 208000023105 Huntington disease Diseases 0.000 claims description 4
• 208000019022 Mood disease Diseases 0.000 claims description 4
• 208000014060 Niemann-Pick disease Diseases 0.000 claims description 4
• 208000018737 Parkinson disease Diseases 0.000 claims description 4
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 210000000988 bone and bone Anatomy 0.000 claims description 4
• 230000006999 cognitive decline Effects 0.000 claims description 4
• 239000003433 contraceptive agent Substances 0.000 claims description 4
• 208000017004 dementia pugilistica Diseases 0.000 claims description 4
• ZVSBVJAMDZKJMH-UHFFFAOYSA-N ethyl 6-(6-cyano-2-hydroxy-1H-indol-3-yl)pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OCC)=CC=C1C1=C(O)NC2=CC(C#N)=CC=C12 ZVSBVJAMDZKJMH-UHFFFAOYSA-N 0.000 claims description 4
• 208000024963 hair loss Diseases 0.000 claims description 4
• MPYRXWRSBIERJA-UHFFFAOYSA-N methyl 3-(4-cyanopyridin-2-yl)-2-hydroxy-1H-indole-5-carboxylate Chemical compound C12=CC(C(=O)OC)=CC=C2NC(O)=C1C1=CC(C#N)=CC=N1 MPYRXWRSBIERJA-UHFFFAOYSA-N 0.000 claims description 4
• KIWOLCMKOZWACI-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-2-oxo-1,3-dihydroindole-5-carboxamide Chemical compound COC1=CC=CC=C1CNC(=O)C1=CC=C(NC(=O)C2)C2=C1 KIWOLCMKOZWACI-UHFFFAOYSA-N 0.000 claims description 4
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 4
• GMEYBCQWFUUMKC-UHFFFAOYSA-N (6-chloro-1-oxidopyridin-1-ium-3-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(Cl)[N+]([O-])=C1 GMEYBCQWFUUMKC-UHFFFAOYSA-N 0.000 claims description 3
• VVGAYLKTCQGMFS-UHFFFAOYSA-N 2-hydroxy-3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C(N)=O)N=C1 VVGAYLKTCQGMFS-UHFFFAOYSA-N 0.000 claims description 3
• QAVVLZHCFJNBLR-UHFFFAOYSA-N 2-hydroxy-3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-5-carboxylic acid Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C(O)=O)N=C1 QAVVLZHCFJNBLR-UHFFFAOYSA-N 0.000 claims description 3
• ZOKSEGBOHQZHQQ-UHFFFAOYSA-N 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.C12=CC(C(=O)N)=CC=C2NC(O)=C1C(N=C1)=CC=C1CN1CCOCC1 ZOKSEGBOHQZHQQ-UHFFFAOYSA-N 0.000 claims description 3
• QTCXKQVDWNKNMJ-UHFFFAOYSA-N 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-N-(oxolan-2-ylmethyl)-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C(=O)NCC3OCCC3)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 QTCXKQVDWNKNMJ-UHFFFAOYSA-N 0.000 claims description 3
• CGWKRTFHAJACSQ-UHFFFAOYSA-N 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-N-[2-(2-oxoimidazolidin-1-yl)ethyl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C(=O)NCCN3C(NCC3)=O)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 CGWKRTFHAJACSQ-UHFFFAOYSA-N 0.000 claims description 3
• QJNVRZGTZREVRM-UHFFFAOYSA-N 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-N-propyl-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.C12=CC(C(=O)NCCC)=CC=C2NC(O)=C1C(N=C1)=CC=C1CN1CCOCC1 QJNVRZGTZREVRM-UHFFFAOYSA-N 0.000 claims description 3
• MDBDHVUPQNDQNN-UHFFFAOYSA-N 2-hydroxy-3-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]-N-(thiophen-2-ylmethyl)-1H-indole-5-carboxamide dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1CC1=CC=C(C=2C3=CC(=CC=C3NC=2O)C(=O)NCC=2SC=CC=2)N=C1 MDBDHVUPQNDQNN-UHFFFAOYSA-N 0.000 claims description 3
• YYGWRUZSBJRPPA-UHFFFAOYSA-N 2-hydroxy-3-[5-[4-(2-pyrrolidin-1-ylethyl)piperazin-1-yl]sulfonylpyridin-2-yl]-1H-indole-6-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC(C#N)=CC=C2C=1C(N=C1)=CC=C1S(=O)(=O)N(CC1)CCN1CCN1CCCC1 YYGWRUZSBJRPPA-UHFFFAOYSA-N 0.000 claims description 3
• XKHYFXGBLVAVED-UHFFFAOYSA-N 2-hydroxy-N-(2-methoxyethyl)-3-(5-morpholin-4-ylsulfonylpyridin-2-yl)-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.C12=CC(C(=O)NCCOC)=CC=C2NC(O)=C1C(N=C1)=CC=C1S(=O)(=O)N1CCOCC1 XKHYFXGBLVAVED-UHFFFAOYSA-N 0.000 claims description 3
• BJRPVBSRBIKJCW-UHFFFAOYSA-N 2-hydroxy-N-(2-methoxyethyl)-3-(5-nitropyridin-2-yl)-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.C12=CC(C(=O)NCCOC)=CC=C2NC(O)=C1C1=CC=C([N+]([O-])=O)C=N1 BJRPVBSRBIKJCW-UHFFFAOYSA-N 0.000 claims description 3
• AMYYUKGKCJKCBI-UHFFFAOYSA-N 2-methylsulfonylethanamine;hydrochloride Chemical compound Cl.CS(=O)(=O)CCN AMYYUKGKCJKCBI-UHFFFAOYSA-N 0.000 claims description 3
• GYEHJHOZNSCDGD-UHFFFAOYSA-N 3-(4-cyanopyridin-2-yl)-2-hydroxy-N-(2-methoxyethyl)-1H-indole-5-carboxamide Chemical compound C12=CC(C(=O)NCCOC)=CC=C2NC(O)=C1C1=CC(C#N)=CC=N1 GYEHJHOZNSCDGD-UHFFFAOYSA-N 0.000 claims description 3
• IJWRUXYFLOESJJ-UHFFFAOYSA-N 3-(5-cyanopyridin-2-yl)-2-hydroxy-N-(2-methoxyethyl)-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.C12=CC(C(=O)NCCOC)=CC=C2NC(O)=C1C1=CC=C(C#N)C=N1 IJWRUXYFLOESJJ-UHFFFAOYSA-N 0.000 claims description 3
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 3
• SPHANZKJWINKIG-UHFFFAOYSA-N 6-(6-cyano-2-hydroxy-1H-indol-3-yl)-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide hydrochloride Chemical compound Cl.OC=1NC2=CC(C#N)=CC=C2C=1C(N=C1)=CC=C1S(=O)(=O)NCCN1CCCC1 SPHANZKJWINKIG-UHFFFAOYSA-N 0.000 claims description 3
• QFBBZPUVXFNUQZ-UHFFFAOYSA-N 6-bromo-2-hydroxy-N-(2-methoxyethyl)-3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.OC=1NC=2C=C(Br)C(C(=O)NCCOC)=CC=2C=1C(N=C1)=CC=C1S(=O)(=O)N1CCN(C)CC1 QFBBZPUVXFNUQZ-UHFFFAOYSA-N 0.000 claims description 3
• IOBHGRBPVCQMNI-UHFFFAOYSA-N 6-chloro-1-oxidopyridin-1-ium-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)[N+]([O-])=C1 IOBHGRBPVCQMNI-UHFFFAOYSA-N 0.000 claims description 3
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• VYRSFIQHMDVTSW-UHFFFAOYSA-N N-(2-amino-2-oxoethyl)-2-hydroxy-3-[5-(4-methylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C(=O)NCC(N)=O)N=C1 VYRSFIQHMDVTSW-UHFFFAOYSA-N 0.000 claims description 3
• SFJGXQHFKZGNQY-UHFFFAOYSA-N N-(cyanomethyl)-2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C(=O)NCC#N)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 SFJGXQHFKZGNQY-UHFFFAOYSA-N 0.000 claims description 3
• GUEVIEGDHKIHNJ-UHFFFAOYSA-N N-benzyl-2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C(=O)NCC=3C=CC=CC=3)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 GUEVIEGDHKIHNJ-UHFFFAOYSA-N 0.000 claims description 3
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• 230000007423 decrease Effects 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• JULFNWVJVZWLHU-UHFFFAOYSA-N ethyl 6-chloro-1-oxidopyridin-1-ium-3-carboxylate Chemical compound CCOC(=O)C1=CC=C(Cl)[N+]([O-])=C1 JULFNWVJVZWLHU-UHFFFAOYSA-N 0.000 claims description 3
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 3
• QYHOFUKEWCIHFR-UHFFFAOYSA-N n-[(6-chloro-1-oxidopyridin-1-ium-3-yl)methyl]-n-ethylethanamine Chemical compound CCN(CC)CC1=CC=C(Cl)[N+]([O-])=C1 QYHOFUKEWCIHFR-UHFFFAOYSA-N 0.000 claims description 3
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