ZA200407665B - New compounds. - Google Patents

New compounds. Download PDF

Info

Publication number: ZA200407665B
Authority: ZA; South Africa
Prior art keywords: pyridin; compound; hydroxy; indol; methyl
Prior art date: 2002-03-28

Application number

ZA200407665A

Other languages

English (en)

Inventor

Stefan Berg

Martin Nyloef

Sven Hellberg

Yafeng Xue

Original Assignee

Astrazeneca Ab

Priority date (The priority date 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 date listed.)

2002-03-28

Filing date

2004-09-22

Publication date

2005-08-29

2004-09-22 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2005-08-29 Publication of ZA200407665B publication Critical patent/ZA200407665B/en

Links

150000001875 compounds Chemical class 0.000 title claims description 154
238000006243 chemical reaction Methods 0.000 claims description 51
229910052717 sulfur Inorganic materials 0.000 claims description 46
229910052760 oxygen Inorganic materials 0.000 claims description 45
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 40
229910052736 halogen Inorganic materials 0.000 claims description 40
150000002367 halogens Chemical group 0.000 claims description 40
108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 claims description 39
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 38
125000005842 heteroatom Chemical group 0.000 claims description 38
238000000034 method Methods 0.000 claims description 36
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
230000002265 prevention Effects 0.000 claims description 35
-1 (CO)OC Chemical group 0.000 claims description 33
125000000623 heterocyclic group Chemical group 0.000 claims description 32
125000000217 alkyl group Chemical group 0.000 claims description 31
229910052739 hydrogen Inorganic materials 0.000 claims description 31
239000001257 hydrogen Substances 0.000 claims description 29
239000002904 solvent Substances 0.000 claims description 28
239000002585 base Substances 0.000 claims description 27
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
239000000203 mixture Substances 0.000 claims description 25
150000003839 salts Chemical class 0.000 claims description 23
125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 22
208000024827 Alzheimer disease Diseases 0.000 claims description 20
239000000460 chlorine Substances 0.000 claims description 19
208000010877 cognitive disease Diseases 0.000 claims description 19
125000001072 heteroaryl group Chemical group 0.000 claims description 19
206010012289 Dementia Diseases 0.000 claims description 18
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
229920006395 saturated elastomer Polymers 0.000 claims description 17
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 16
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 16
229910052794 bromium Inorganic materials 0.000 claims description 16
239000003153 chemical reaction reagent Substances 0.000 claims description 16
229910052801 chlorine Inorganic materials 0.000 claims description 16
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
229910052731 fluorine Inorganic materials 0.000 claims description 15
229910052757 nitrogen Inorganic materials 0.000 claims description 15
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 13
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 13
239000011737 fluorine Substances 0.000 claims description 13
125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims description 13
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 13
201000011240 Frontotemporal dementia Diseases 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
125000004429 atom Chemical group 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 12
206010027175 memory impairment Diseases 0.000 claims description 12
230000008569 process Effects 0.000 claims description 12
241000124008 Mammalia Species 0.000 claims description 11
150000001412 amines Chemical class 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 11
201000004384 Alopecia Diseases 0.000 claims description 10
229910052799 carbon Inorganic materials 0.000 claims description 10
201000010099 disease Diseases 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 10
208000020925 Bipolar disease Diseases 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
239000012458 free base Substances 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 8
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 8
201000000980 schizophrenia Diseases 0.000 claims description 8
125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 7
208000028698 Cognitive impairment Diseases 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
230000004770 neurodegeneration Effects 0.000 claims description 7
208000015122 neurodegenerative disease Diseases 0.000 claims description 7
238000010992 reflux Methods 0.000 claims description 7
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 6
206010019196 Head injury Diseases 0.000 claims description 6
208000027089 Parkinsonian disease Diseases 0.000 claims description 6
206010034010 Parkinsonism Diseases 0.000 claims description 6
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
230000001684 chronic effect Effects 0.000 claims description 6
230000003676 hair loss Effects 0.000 claims description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
208000011990 Corticobasal Degeneration Diseases 0.000 claims description 5
201000010374 Down Syndrome Diseases 0.000 claims description 5
208000023105 Huntington disease Diseases 0.000 claims description 5
208000019022 Mood disease Diseases 0.000 claims description 5
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 5
208000014060 Niemann-Pick disease Diseases 0.000 claims description 5
208000018737 Parkinson disease Diseases 0.000 claims description 5
208000000609 Pick Disease of the Brain Diseases 0.000 claims description 5
230000006999 cognitive decline Effects 0.000 claims description 5
239000003433 contraceptive agent Substances 0.000 claims description 5
230000007423 decrease Effects 0.000 claims description 5
208000017004 dementia pugilistica Diseases 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
208000024963 hair loss Diseases 0.000 claims description 5
230000007170 pathology Effects 0.000 claims description 5
201000002212 progressive supranuclear palsy Diseases 0.000 claims description 5
238000002560 therapeutic procedure Methods 0.000 claims description 5
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 4
206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 4
201000002832 Lewy body dementia Diseases 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
206010068168 androgenetic alopecia Diseases 0.000 claims description 4
201000002996 androgenic alopecia Diseases 0.000 claims description 4
230000002254 contraceptive effect Effects 0.000 claims description 4
229940079593 drug Drugs 0.000 claims description 4
235000005152 nicotinamide Nutrition 0.000 claims description 4
239000011570 nicotinamide Substances 0.000 claims description 4
229960003966 nicotinamide Drugs 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
125000004043 oxo group Chemical group O=* 0.000 claims description 4
208000037658 Parkinson-dementia complex of Guam Diseases 0.000 claims description 3
201000004810 Vascular dementia Diseases 0.000 claims description 3
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 3
230000001149 cognitive effect Effects 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 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
QCYPSFQGPOIENZ-WLHGVMLRSA-N (E)-but-2-enedioic acid 6-(5-cyano-2-hydroxy-1H-indol-3-yl)-N-(2-pyrrolidin-1-ylethyl)pyridine-3-carboxamide Chemical compound OC(=O)\C=C\C(O)=O.Oc1[nH]c2ccc(C#N)cc2c1-c(nc1)ccc1C(=O)NCCN1CCCC1 QCYPSFQGPOIENZ-WLHGVMLRSA-N 0.000 claims description 2
RXYFRVCSXAWEJR-WLHGVMLRSA-N (E)-but-2-enedioic acid 6-(5-cyano-2-hydroxy-1H-indol-3-yl)-N-[(1-ethylpyrrolidin-2-yl)methyl]pyridine-3-sulfonamide Chemical compound OC(=O)\C=C\C(O)=O.CCN1CCCC1CNS(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 RXYFRVCSXAWEJR-WLHGVMLRSA-N 0.000 claims description 2
FZVZMDOGYBGFTL-WLHGVMLRSA-N (E)-but-2-enedioic acid 6-(5-cyano-2-hydroxy-1H-indol-3-yl)-N-[2-(dimethylamino)ethyl]-N-ethylpyridine-3-sulfonamide Chemical compound OC(=O)\C=C\C(O)=O.N1=CC(S(=O)(=O)N(CCN(C)C)CC)=CC=C1C1=C(O)NC2=CC=C(C#N)C=C12 FZVZMDOGYBGFTL-WLHGVMLRSA-N 0.000 claims description 2
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 2
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 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
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 2
QEGKDXPEXXJSBJ-UHFFFAOYSA-N 2-hydroxy-3-[5-(4-propan-2-ylpiperazin-1-yl)sulfonylpyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.C1CN(C(C)C)CCN1S(=O)(=O)C1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 QEGKDXPEXXJSBJ-UHFFFAOYSA-N 0.000 claims description 2
BBGBUCAWBPAOKB-UHFFFAOYSA-N 2-hydroxy-3-[5-(pyrrolidin-1-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN1CCCC1 BBGBUCAWBPAOKB-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
AICZIXZCGTTZLV-UHFFFAOYSA-N 2-hydroxy-3-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride Chemical compound Cl.C1CN(C)CCN1CC1=CC=C(C=2C3=CC(=CC=C3NC=2O)C#N)N=C1 AICZIXZCGTTZLV-UHFFFAOYSA-N 0.000 claims description 2
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 2
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 2
BCJXCAKHQLKPLH-UHFFFAOYSA-N 2-hydroxy-3-[6-(2-morpholin-4-ylethoxy)pyrimidin-4-yl]-1H-indole-5-carbonitrile Chemical compound OC=1NC2=CC=C(C#N)C=C2C=1C(N=CN=1)=CC=1OCCN1CCOCC1 BCJXCAKHQLKPLH-UHFFFAOYSA-N 0.000 claims description 2
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 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
XYUBCWOJCJVECF-UHFFFAOYSA-N 3-[5-(azetidin-1-ylmethyl)pyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile Chemical compound OC=1NC2=CC=C(C#N)C=C2C=1C(N=C1)=CC=C1CN1CCC1 XYUBCWOJCJVECF-UHFFFAOYSA-N 0.000 claims description 2
JNWPMVNHJYNDFH-UHFFFAOYSA-N 3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-indol-2-ol Chemical compound OC=1NC2=CC=C(C(F)(F)F)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 JNWPMVNHJYNDFH-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
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 2
DGYOQSAUPDVPQH-UHFFFAOYSA-N 3-fluoro-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-2-oxo-1h-indole-6-carbonitrile;hydrochloride Chemical compound Cl.O=C1NC2=CC(C#N)=CC=C2C1(F)C(N=C1)=CC=C1CN1CCOCC1 DGYOQSAUPDVPQH-UHFFFAOYSA-N 0.000 claims description 2
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 2
CEVWVQYKVWVJFO-UHFFFAOYSA-N 6-(2-hydroxy-5-nitro-1H-indol-3-yl)-N-(2-morpholin-4-ylethyl)pyridine-3-carboxamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C([N+]([O-])=O)C=C2C=1C(N=C1)=CC=C1C(=O)NCCN1CCOCC1 CEVWVQYKVWVJFO-UHFFFAOYSA-N 0.000 claims description 2
KFXQVCKZFXCCCN-UHFFFAOYSA-N 6-(2-hydroxy-5-nitro-1H-indol-3-yl)-N-methyl-N-(1-methylpiperidin-4-yl)pyridine-3-carboxamide hydrochloride Chemical compound Cl.C=1C=C(C=2C3=CC(=CC=C3NC=2O)[N+]([O-])=O)N=CC=1C(=O)N(C)C1CCN(C)CC1 KFXQVCKZFXCCCN-UHFFFAOYSA-N 0.000 claims description 2
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 2
GFRMJDAREJXJMH-UHFFFAOYSA-N 6-(5-cyano-2-hydroxy-1H-indol-3-yl)-N-[2-(dimethylamino)ethyl]-N-methylpyridine-3-carboxamide hydrochloride Chemical compound Cl.N1=CC(C(=O)N(C)CCN(C)C)=CC=C1C1=C(O)NC2=CC=C(C#N)C=C12 GFRMJDAREJXJMH-UHFFFAOYSA-N 0.000 claims description 2
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 2
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 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
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 2
230000009467 reduction Effects 0.000 claims description 2
239000000126 substance Substances 0.000 claims 18
102000001267 GSK3 Human genes 0.000 claims 4
230000007000 age related cognitive decline Effects 0.000 claims 3
125000005843 halogen group Chemical group 0.000 claims 3
208000027061 mild cognitive impairment Diseases 0.000 claims 3
238000009472 formulation Methods 0.000 claims 2
OJSUZRNVWYHBNS-UHFFFAOYSA-N (2-chloropyridin-4-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=NC(Cl)=C1 OJSUZRNVWYHBNS-UHFFFAOYSA-N 0.000 claims 1
DMXGFDSGVSISBY-UHFFFAOYSA-N 1-(5-bromo-6-chloropyridin-3-yl)sulfonyl-4-methylpiperazine Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CN=C(Cl)C(Br)=C1 DMXGFDSGVSISBY-UHFFFAOYSA-N 0.000 claims 1
JIVHZSMTMHEIIJ-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)sulfonyl-4-(3-methylbutyl)piperazine Chemical compound C1CN(CCC(C)C)CCN1S(=O)(=O)C1=CC=C(Cl)N=C1 JIVHZSMTMHEIIJ-UHFFFAOYSA-N 0.000 claims 1
IHNXDZSFVAKMPS-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)sulfonyl-4-ethylpiperazine Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CC=C(Cl)N=C1 IHNXDZSFVAKMPS-UHFFFAOYSA-N 0.000 claims 1
APIKVTIQATUVSW-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)sulfonyl-4-methyl-1,4-diazepane Chemical compound C1CN(C)CCCN1S(=O)(=O)C1=CC=C(Cl)N=C1 APIKVTIQATUVSW-UHFFFAOYSA-N 0.000 claims 1
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ZA200407665A 2002-03-28 2004-09-22 New compounds. ZA200407665B (en)

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JP (2)	JP3989444B2 (pl)
KR (1)	KR101014525B1 (pl)
CN (2)	CN100519550C (pl)
AR (1)	AR038996A1 (pl)
AT (1)	ATE416171T1 (pl)
AU (1)	AU2003216026B2 (pl)
BR (1)	BR0308196A (pl)
CA (1)	CA2476343C (pl)
CY (1)	CY1108823T1 (pl)
DE (1)	DE60325032D1 (pl)
DK (1)	DK1492785T3 (pl)
ES (1)	ES2316784T3 (pl)
IL (2)	IL163894A0 (pl)
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SE (1)	SE0200979D0 (pl)
SI (1)	SI1492785T1 (pl)
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UA (1)	UA79447C2 (pl)
UY (1)	UY27740A1 (pl)
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SE0302546D0 (sv) *	2003-09-24	2003-09-24	Astrazeneca Ab	New compounds
US20040067985A1 (en) *	2002-10-04	2004-04-08	Fortuna Haviv	Method of inhibiting angiogenesis
WO2006023931A2 (en)	2004-08-18	2006-03-02	Takeda San Diego, Inc.	Kinase inhibitors
EP1812439B2 (en)	2004-10-15	2017-12-06	Takeda Pharmaceutical Company Limited	Kinase inhibitors
US20060282228A1 (en) *	2005-06-10	2006-12-14	Pioneer Hi-Bred International, Inc.	Method and system for use of environmental classification in precision farming
AU2006282896A1 (en)	2005-08-26	2007-03-01	Braincells, Inc.	Neurogenesis by muscarinic receptor modulation
EP2258359A3 (en)	2005-08-26	2011-04-06	Braincells, Inc.	Neurogenesis by muscarinic receptor modulation with sabcomelin
US8119655B2 (en)	2005-10-07	2012-02-21	Takeda Pharmaceutical Company Limited	Kinase inhibitors
AU2006304787A1 (en)	2005-10-21	2007-04-26	Braincells, Inc.	Modulation of neurogenesis by PDE inhibition
EP2314289A1 (en)	2005-10-31	2011-04-27	Braincells, Inc.	Gaba receptor mediated modulation of neurogenesis
WO2007089193A1 (en) *	2006-02-02	2007-08-09	Astrazeneca Ab	A process for preparing 2-hydroxy-3- [5- (morpholin-4-ylmethyl)pyridin-2-yl] lh-indole-5-carbonitrile as a free base or salts thereof
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Publication number	Publication date
SE0200979D0 (sv)	2002-03-28
PL372966A1 (pl)	2005-08-08
MXPA04009163A (es)	2004-12-07
SI1492785T1 (sl)	2009-06-30
TW200306180A (en)	2003-11-16
DK1492785T3 (da)	2009-03-02
RU2004125146A (ru)	2005-06-27
US20090149460A1 (en)	2009-06-11
AU2003216026A1 (en)	2003-10-13
EP1961748A2 (en)	2008-08-27
KR20040094884A (ko)	2004-11-10
WO2003082853A8 (en)	2004-05-06
CN100519550C (zh)	2009-07-29
PT1492785E (pt)	2009-02-02
KR101014525B1 (ko)	2011-02-14
EP1492785B1 (en)	2008-12-03
HK1071360A1 (en)	2005-07-15
IL163894A0 (en)	2005-12-18
SA03240054B1 (ar)	2009-04-04
NO20044432L (no)	2004-10-19
RU2338742C2 (ru)	2008-11-20
NZ534664A (en)	2007-06-29
MY144659A (en)	2011-10-31
EP1492785B9 (en)	2009-10-21
JP2007224051A (ja)	2007-09-06
NO329884B1 (no)	2011-01-17
EP1961748A3 (en)	2009-10-07
JP3989444B2 (ja)	2007-10-10
AR038996A1 (es)	2005-02-02
BR0308196A (pt)	2005-01-11
ATE416171T1 (de)	2008-12-15
IL163894A (en)	2010-11-30
UY27740A1 (es)	2003-10-31
UA79447C2 (en)	2007-06-25
JP2005526814A (ja)	2005-09-08
CN1923812A (zh)	2007-03-07
ES2316784T3 (es)	2009-04-16
AU2003216026B2 (en)	2008-12-11
US20050153987A1 (en)	2005-07-14
TWI330081B (en)	2010-09-11
WO2003082853A1 (en)	2003-10-09
CA2476343C (en)	2011-05-03
CN1642938A (zh)	2005-07-20
CY1108823T1 (el)	2014-04-09
DE60325032D1 (de)	2009-01-15
PL211096B1 (pl)	2012-04-30
IS7471A (is)	2004-10-15
CA2476343A1 (en)	2003-10-09
US7399780B2 (en)	2008-07-15
EP1492785A1 (en)	2005-01-05

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AU2003287137B2 (en)	2007-07-05	Novel compounds having selective inhibiting effect at GSK3
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HK1120512A (en)	2009-04-03	2-hydroxy-3-heteroarylindole derivatives as gsk3 inhibitors
HK1071360B (en)	2009-07-03	2-hydroxy-3-heteroarylindole derivatives as gsk3 inhibitors