MXPA06003195A

MXPA06003195A - Derivados de 3-heterociclil-indol como inhibidores de glicogeno sintasa cinasa-3 (gsk-3).

Derivados de 3-heterociclil-indol como inhibidores de glicogeno sintasa cinasa-3 (gsk-3).

Info

Publication number: MXPA06003195A
Authority: MX; Mexico
Prior art keywords: hydroxy; indole; hydrochloride; carboxamide; pyridin
Prior art date: 2003-09-24

Application number

MXPA06003195A

Other languages

English (en)

Spanish (es)

Inventor

Sven Hellberg

Original Assignee

Astrazeneca Ab

Priority date

2003-09-24

Filing date

2004-09-21

Publication date

2006-06-23

2004-09-21 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2006-06-23 Publication of MXPA06003195A publication Critical patent/MXPA06003195A/es

Links

108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 title claims description 39
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 283
150000003839 salts Chemical class 0.000 claims abstract description 38
238000000034 method Methods 0.000 claims abstract description 36
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
238000002360 preparation method Methods 0.000 claims abstract description 22
239000012458 free base Substances 0.000 claims abstract description 21
230000008569 process Effects 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
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 13
229910052757 nitrogen 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 7
229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 4
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
-1 { 5- [(4-methylpiperazin-1-yl) carbonyl] pyridin-2-yl) -lH-indole-6-carbonitrile Chemical compound 0.000 claims description 251
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 114
239000002585 base Substances 0.000 claims description 112
125000000217 alkyl group Chemical group 0.000 claims description 104
238000006243 chemical reaction Methods 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 93
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 84
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 80
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 43
150000001412 amines Chemical class 0.000 claims description 35
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 30
239000003153 chemical reaction reagent Substances 0.000 claims description 29
125000000623 heterocyclic group Chemical group 0.000 claims description 29
230000002265 prevention Effects 0.000 claims description 28
239000002253 acid Substances 0.000 claims description 26
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
206010012289 Dementia Diseases 0.000 claims description 20
125000005843 halogen group Chemical group 0.000 claims description 20
208000024827 Alzheimer disease Diseases 0.000 claims description 18
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 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
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 15
208000010877 cognitive disease Diseases 0.000 claims description 15
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 14
125000002877 alkyl aryl group Chemical group 0.000 claims description 13
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 13
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 12
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 11
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
238000010992 reflux Methods 0.000 claims description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 10
241000124008 Mammalia Species 0.000 claims description 9
201000010099 disease Diseases 0.000 claims description 9
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 9
201000004384 Alopecia Diseases 0.000 claims description 8
201000011240 Frontotemporal dementia Diseases 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
150000003973 alkyl amines Chemical class 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
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
208000035475 disorder Diseases 0.000 claims description 7
230000006870 function Effects 0.000 claims description 7
206010027175 memory impairment Diseases 0.000 claims description 7
201000000980 schizophrenia Diseases 0.000 claims description 7
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 6
208000020925 Bipolar disease Diseases 0.000 claims description 6
XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 claims description 6
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 6
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
206010012601 diabetes mellitus Diseases 0.000 claims description 6
230000026030 halogenation Effects 0.000 claims description 6
238000005658 halogenation reaction Methods 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
230000004770 neurodegeneration Effects 0.000 claims description 6
208000015122 neurodegenerative disease Diseases 0.000 claims description 6
210000002682 neurofibrillary tangle Anatomy 0.000 claims description 6
125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 6
PXJACNDVRNAFHD-UHFFFAOYSA-N (2-methoxyphenyl)methanamine Chemical compound COC1=CC=CC=C1CN PXJACNDVRNAFHD-UHFFFAOYSA-N 0.000 claims description 5
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 5
206010019196 Head injury Diseases 0.000 claims description 5
208000018737 Parkinson disease Diseases 0.000 claims description 5
208000027089 Parkinsonian disease Diseases 0.000 claims description 5
206010034010 Parkinsonism Diseases 0.000 claims description 5
125000003545 alkoxy group Chemical group 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
GRRIMVWABNHKBX-UHFFFAOYSA-N (3-methoxyphenyl)methanamine Chemical compound COC1=CC=CC(CN)=C1 GRRIMVWABNHKBX-UHFFFAOYSA-N 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 4
IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 claims description 4
208000028698 Cognitive impairment Diseases 0.000 claims description 4
208000011990 Corticobasal Degeneration Diseases 0.000 claims description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 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
230000003213 activating effect Effects 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
210000000988 bone and bone Anatomy 0.000 claims description 4
230000001149 cognitive effect Effects 0.000 claims description 4
239000003433 contraceptive agent Substances 0.000 claims description 4
208000024963 hair loss Diseases 0.000 claims description 4
PGKRDJHKIISUEY-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-2-oxo-1,3-dihydroindole-5-carboxamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=C3CC(=O)NC3=CC=2)=C1 PGKRDJHKIISUEY-UHFFFAOYSA-N 0.000 claims description 4
VQHUCMCIWMZMDP-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-2-oxo-1,3-dihydroindole-5-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(NC(=O)C2)C2=C1 VQHUCMCIWMZMDP-UHFFFAOYSA-N 0.000 claims description 4
XHQSKBZJTKNTAV-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-2-oxo-1,3-dihydroindole-5-carboxamide Chemical compound CN(C)CCNC(=O)C1=CC=C2NC(=O)CC2=C1 XHQSKBZJTKNTAV-UHFFFAOYSA-N 0.000 claims description 4
201000002212 progressive supranuclear palsy Diseases 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
UNXDMJTYLDHOSQ-UHFFFAOYSA-N 2-hydroxy-3-[5-(piperidin-1-ylmethyl)pyridin-2-yl]-1H-indole-6-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC(C#N)=CC=C2C=1C(N=C1)=CC=C1CN1CCCCC1 UNXDMJTYLDHOSQ-UHFFFAOYSA-N 0.000 claims description 3
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 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
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 3
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 3
XQYHNVBDRXQOGY-UHFFFAOYSA-N ClC1=CC(=NC=N1)OCCCC(C)NC(C)C Chemical compound ClC1=CC(=NC=N1)OCCCC(C)NC(C)C XQYHNVBDRXQOGY-UHFFFAOYSA-N 0.000 claims description 3
206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 3
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
201000010374 Down Syndrome Diseases 0.000 claims description 3
201000002832 Lewy body dementia Diseases 0.000 claims description 3
208000000609 Pick Disease of the Brain Diseases 0.000 claims description 3
208000006011 Stroke Diseases 0.000 claims description 3
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
201000004810 Vascular dementia Diseases 0.000 claims description 3
206010068168 androgenetic alopecia Diseases 0.000 claims description 3
201000002996 androgenic alopecia Diseases 0.000 claims description 3
230000006999 cognitive decline Effects 0.000 claims description 3
230000002254 contraceptive effect Effects 0.000 claims description 3
125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 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
229940064982 ethylnicotinate Drugs 0.000 claims description 3
238000003682 fluorination reaction Methods 0.000 claims description 3
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 3
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 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
208000027061 mild cognitive impairment Diseases 0.000 claims description 3
SLGCBXXXLUKEKX-UHFFFAOYSA-N n-(2-cyanoethyl)-2-oxo-1,3-dihydroindole-5-carboxamide Chemical compound N#CCCNC(=O)C1=CC=C2NC(=O)CC2=C1 SLGCBXXXLUKEKX-UHFFFAOYSA-N 0.000 claims description 3
KBROTFGEOBLMGP-UHFFFAOYSA-N n-(3-methoxypropyl)-2-oxo-1,3-dihydroindole-5-carboxamide Chemical compound COCCCNC(=O)C1=CC=C2NC(=O)CC2=C1 KBROTFGEOBLMGP-UHFFFAOYSA-N 0.000 claims description 3
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 3
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
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 2
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 2
IJVVJCPEIIGOMP-UHFFFAOYSA-N 2-hydroxy-3-(5-piperazin-1-ylsulfonylpyridin-2-yl)-1H-indole-6-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC(C#N)=CC=C2C=1C(N=C1)=CC=C1S(=O)(=O)N1CCNCC1 IJVVJCPEIIGOMP-UHFFFAOYSA-N 0.000 claims description 2
KGVZUWKTNPMHRE-UHFFFAOYSA-N 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-N-[[2-(trifluoromethoxy)phenyl]methyl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C(=O)NCC=3C(=CC=CC=3)OC(F)(F)F)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 KGVZUWKTNPMHRE-UHFFFAOYSA-N 0.000 claims description 2
SHJHLDMFIALEGG-UHFFFAOYSA-N 2-hydroxy-3-[5-(piperidin-1-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.C12=CC(C(=O)N)=CC=C2NC(O)=C1C(N=C1)=CC=C1CN1CCCCC1 SHJHLDMFIALEGG-UHFFFAOYSA-N 0.000 claims description 2
WCBGYKJQTCLWJI-UHFFFAOYSA-N 2-hydroxy-3-[6-(2-morpholin-4-ylethoxy)pyrimidin-4-yl]-1H-indole-6-carbonitrile hydrochloride Chemical compound Cl.OC=1NC2=CC(C#N)=CC=C2C=1C(N=CN=1)=CC=1OCCN1CCOCC1 WCBGYKJQTCLWJI-UHFFFAOYSA-N 0.000 claims description 2
125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 2
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 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
UAWMVMPAYRWUFX-UHFFFAOYSA-N 6-Chloronicotinic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1 UAWMVMPAYRWUFX-UHFFFAOYSA-N 0.000 claims description 2
NCUHRGBJLYQQNH-UHFFFAOYSA-N 6-bromo-2-oxo-n-(2-pyrrolidin-1-ylethyl)-1,3-dihydroindole-5-carboxamide Chemical compound BrC1=CC=2NC(=O)CC=2C=C1C(=O)NCCN1CCCC1 NCUHRGBJLYQQNH-UHFFFAOYSA-N 0.000 claims description 2
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 2
MVDVEAQYXYHYHM-UHFFFAOYSA-N N-benzyl-2-hydroxy-3-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]-1H-indole-5-carboxamide dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1CC1=CC=C(C=2C3=CC(=CC=C3NC=2O)C(=O)NCC=2C=CC=CC=2)N=C1 MVDVEAQYXYHYHM-UHFFFAOYSA-N 0.000 claims description 2
231100000876 cognitive deterioration Toxicity 0.000 claims description 2
230000006866 deterioration Effects 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
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125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
GQMYQEAXTITUAE-UHFFFAOYSA-N 1H-indole-5-carboxamide Chemical compound NC(=O)C1=CC=C2NC=CC2=C1 GQMYQEAXTITUAE-UHFFFAOYSA-N 0.000 claims 1
PPMZZEYLHMSUPM-UHFFFAOYSA-N 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-N-[[4-(trifluoromethoxy)phenyl]methyl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C(=O)NCC=3C=CC(OC(F)(F)F)=CC=3)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 PPMZZEYLHMSUPM-UHFFFAOYSA-N 0.000 claims 1
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 1
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 1
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 1
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 1
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 1
CNYFJXWZEHZDJH-UHFFFAOYSA-N N-(2-cyanoethyl)-2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochloride Chemical compound Cl.OC=1NC2=CC=C(C(=O)NCCC#N)C=C2C=1C(N=C1)=CC=C1CN1CCOCC1 CNYFJXWZEHZDJH-UHFFFAOYSA-N 0.000 claims 1
206010036590 Premature baby Diseases 0.000 claims 1
230000006735 deficit Effects 0.000 claims 1
WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 claims 1
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