ZA200407665B - New compounds. - Google Patents
New compounds. Download PDFInfo
- Publication number
- ZA200407665B ZA200407665B ZA200407665A ZA200407665A ZA200407665B ZA 200407665 B ZA200407665 B ZA 200407665B ZA 200407665 A ZA200407665 A ZA 200407665A ZA 200407665 A ZA200407665 A ZA 200407665A ZA 200407665 B ZA200407665 B ZA 200407665B
- Authority
- ZA
- South Africa
- Prior art keywords
- pyridin
- compound
- hydroxy
- indol
- methyl
- Prior art date
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
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- 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
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0200979A SE0200979D0 (sv) | 2002-03-28 | 2002-03-28 | New compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200407665B true ZA200407665B (en) | 2005-08-29 |
Family
ID=20287447
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200407665A ZA200407665B (en) | 2002-03-28 | 2004-09-22 | New compounds. |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US7399780B2 (ru) |
| EP (2) | EP1961748A3 (ru) |
| JP (2) | JP3989444B2 (ru) |
| KR (1) | KR101014525B1 (ru) |
| CN (2) | CN100519550C (ru) |
| AR (1) | AR038996A1 (ru) |
| AT (1) | ATE416171T1 (ru) |
| AU (1) | AU2003216026B2 (ru) |
| BR (1) | BR0308196A (ru) |
| CA (1) | CA2476343C (ru) |
| CY (1) | CY1108823T1 (ru) |
| DE (1) | DE60325032D1 (ru) |
| DK (1) | DK1492785T3 (ru) |
| ES (1) | ES2316784T3 (ru) |
| HK (1) | HK1071360A1 (ru) |
| IL (2) | IL163894A0 (ru) |
| IS (1) | IS7471A (ru) |
| MX (1) | MXPA04009163A (ru) |
| MY (1) | MY144659A (ru) |
| NO (1) | NO329884B1 (ru) |
| NZ (1) | NZ534664A (ru) |
| PL (1) | PL211096B1 (ru) |
| PT (1) | PT1492785E (ru) |
| RU (1) | RU2338742C2 (ru) |
| SA (1) | SA03240054B1 (ru) |
| SE (1) | SE0200979D0 (ru) |
| SI (1) | SI1492785T1 (ru) |
| TW (1) | TWI330081B (ru) |
| UA (1) | UA79447C2 (ru) |
| UY (1) | UY27740A1 (ru) |
| WO (1) | WO2003082853A1 (ru) |
| ZA (1) | ZA200407665B (ru) |
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| PT2970890T (pt) | 2013-03-14 | 2020-04-24 | Massachusetts Inst Technology | Composições e métodos para expansão e cultura de células estaminais epiteliais |
| WO2016008966A1 (en) | 2014-07-17 | 2016-01-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for treating neuromuscular junction-related diseases |
| KR20230019500A (ko) | 2014-09-03 | 2023-02-08 | 더 브리검 앤드 우먼즈 하스피털, 인크. | 청력 손실의 치료를 위해 내이 털세포를 생성하기 위한 조성물, 시스템, 및 방법 |
| WO2016207366A1 (en) | 2015-06-26 | 2016-12-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of viral infections |
| GB201519573D0 (en) | 2015-11-05 | 2015-12-23 | King S College London | Combination |
| JP2019506153A (ja) | 2016-01-08 | 2019-03-07 | マサチューセッツ インスティテュート オブ テクノロジー | 分化した腸内分泌細胞およびインスリン産生細胞の作製 |
| US10201540B2 (en) | 2016-03-02 | 2019-02-12 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: I |
| US11260130B2 (en) | 2016-03-02 | 2022-03-01 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: IV |
| US10213511B2 (en) | 2016-03-02 | 2019-02-26 | Frequency Therapeutics, Inc. | Thermoreversible compositions for administration of therapeutic agents |
| RU2648820C2 (ru) * | 2016-04-14 | 2018-03-28 | Общество с ограниченной ответственностью "Научно-исследовательский центр "Парк активных молекул" | Средство, обладающее противоклоногенной активностью в отношении опухолевых клеток человека |
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| AU2019321641A1 (en) | 2018-08-17 | 2021-04-15 | Frequency Therapeutics, Inc. | Compositions and methods for generating hair cells by upregulating Jag-1 |
| WO2020037326A1 (en) | 2018-08-17 | 2020-02-20 | Frequency Therapeutics, Inc. | Compositions and methods for generating hair cells by downregulating foxo |
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| TW200301123A (en) | 2001-12-21 | 2003-07-01 | Astrazeneca Uk Ltd | New use |
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- 2003-03-28 KR KR1020047015389A patent/KR101014525B1/ko not_active IP Right Cessation
- 2003-03-28 UY UY27740A patent/UY27740A1/es not_active Application Discontinuation
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- 2003-03-28 RU RU2004125146/04A patent/RU2338742C2/ru not_active IP Right Cessation
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- 2003-03-28 CN CNB038073897A patent/CN100519550C/zh not_active Expired - Fee Related
- 2003-03-28 ES ES03745498T patent/ES2316784T3/es not_active Expired - Lifetime
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