KR20100054856A - 히스타민-3 길항제로서의 이소퀴놀리닐 및 이소인돌리닐 유도체 - Google Patents

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Publication number

KR20100054856A

KR20100054856A KR1020107007943A KR20107007943A KR20100054856A KR 20100054856 A KR20100054856 A KR 20100054856A KR 1020107007943 A KR1020107007943 A KR 1020107007943A KR 20107007943 A KR20107007943 A KR 20107007943A KR 20100054856 A KR20100054856 A KR 20100054856A

Authority

KR

South Korea

Prior art keywords

pyrrolidin

ylethyl

oxo

ethyl

tetrahydroisoquinolin

Prior art date

2007-09-12

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.)

Ceased

Links

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• Global Dossier
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• 239000005557 antagonist Substances 0.000 title description 7
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 title description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 253
• 238000011282 treatment Methods 0.000 claims abstract description 19
• -1 cycloheteroalkyl Chemical group 0.000 claims description 218
• 238000000034 method Methods 0.000 claims description 116
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 79
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 45
• 150000003839 salts Chemical class 0.000 claims description 39
• 208000010877 cognitive disease Diseases 0.000 claims description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
• 229910052757 nitrogen Inorganic materials 0.000 claims description 30
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 25
• 208000024827 Alzheimer disease Diseases 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
• 229910052760 oxygen Inorganic materials 0.000 claims description 23
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 22
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 20
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 20
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 206010012289 Dementia Diseases 0.000 claims description 16
• 208000035475 disorder Diseases 0.000 claims description 14
• 201000000980 schizophrenia Diseases 0.000 claims description 14
• 208000018737 Parkinson disease Diseases 0.000 claims description 13
• 125000001188 haloalkyl group Chemical group 0.000 claims description 13
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 9
• 208000023105 Huntington disease Diseases 0.000 claims description 8
• 125000003342 alkenyl group Chemical group 0.000 claims description 8
• 229910052739 hydrogen Inorganic materials 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 239000002904 solvent Substances 0.000 claims description 8
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 8
• 208000026139 Memory disease Diseases 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• 201000004810 Vascular dementia Diseases 0.000 claims description 6
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 206010027175 memory impairment Diseases 0.000 claims description 6
• 208000028017 Psychotic disease Diseases 0.000 claims description 5
• 125000002619 bicyclic group Chemical group 0.000 claims description 5
• 230000006870 function Effects 0.000 claims description 5
• 230000013016 learning Effects 0.000 claims description 5
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
• LZTSCEYDCZBRCJ-UHFFFAOYSA-N 1,2-dihydro-1,2,4-triazol-3-one Chemical class OC=1N=CNN=1 LZTSCEYDCZBRCJ-UHFFFAOYSA-N 0.000 claims description 4
• 150000005072 1,3,4-oxadiazoles Chemical class 0.000 claims description 4
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 4
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
• DSPDNROSUXQSCT-UHFFFAOYSA-N 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 DSPDNROSUXQSCT-UHFFFAOYSA-N 0.000 claims description 4
• 208000000044 Amnesia Diseases 0.000 claims description 4
• 208000020401 Depressive disease Diseases 0.000 claims description 4
• 208000012239 Developmental disease Diseases 0.000 claims description 4
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
• 206010033864 Paranoia Diseases 0.000 claims description 4
• 208000027099 Paranoid disease Diseases 0.000 claims description 4
• 239000002253 acid Substances 0.000 claims description 4
• 125000000304 alkynyl group Chemical group 0.000 claims description 4
• 230000006999 cognitive decline Effects 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 230000006984 memory degeneration Effects 0.000 claims description 4
• 208000023060 memory loss Diseases 0.000 claims description 4
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 4
• 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 3
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 3
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 3
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 3
• 206010012218 Delirium Diseases 0.000 claims description 3
• 201000010374 Down Syndrome Diseases 0.000 claims description 3
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 3
• 206010019196 Head injury Diseases 0.000 claims description 3
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
• 206010013932 dyslexia Diseases 0.000 claims description 3
• LKTBYJWWCWTBPL-UHFFFAOYSA-N methyl 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 LKTBYJWWCWTBPL-UHFFFAOYSA-N 0.000 claims description 3
• IIQVHLRPDRFQHC-UHFFFAOYSA-N 1-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]indole-5-carbonitrile Chemical compound C1CC2=CC(N3C4=CC=C(C=C4C=C3)C#N)=CC=C2C(=O)N1CCN1CCCC1 IIQVHLRPDRFQHC-UHFFFAOYSA-N 0.000 claims description 2
• YFURTEYAEPSLFX-UHFFFAOYSA-N 2-(2-pyrrolidin-1-ylethyl)-6-[3-(trifluoromethoxy)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound FC(F)(F)OC1=CC=CC(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)=C1 YFURTEYAEPSLFX-UHFFFAOYSA-N 0.000 claims description 2
• YGDXRYIZHALWOY-UHFFFAOYSA-N 2-(2-pyrrolidin-1-ylethyl)-6-[3-(trifluoromethyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound FC(F)(F)C1=CC=CC(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)=C1 YGDXRYIZHALWOY-UHFFFAOYSA-N 0.000 claims description 2
• SXUZRGLZTPXKSU-UHFFFAOYSA-N 2-(2-pyrrolidin-1-ylethyl)-6-[4-(trifluoromethoxy)phenyl]-3,4-dihydro-1h-isoquinoline Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1=CC=C(CN(CCN2CCCC2)CC2)C2=C1 SXUZRGLZTPXKSU-UHFFFAOYSA-N 0.000 claims description 2
• UZARNTGJNZJLMB-UHFFFAOYSA-N 2-(2-pyrrolidin-1-ylethyl)-6-[4-(trifluoromethoxy)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 UZARNTGJNZJLMB-UHFFFAOYSA-N 0.000 claims description 2
• IZGHSNVQGBODFP-UHFFFAOYSA-N 2-(2-pyrrolidin-1-ylethyl)-6-[4-(trifluoromethyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 IZGHSNVQGBODFP-UHFFFAOYSA-N 0.000 claims description 2
• LVGUHWADRXKKTN-MRXNPFEDSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-n-pyridin-4-yl-3,4-dihydroisoquinoline-6-carboxamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)NC=3C=CN=CC=3)C=C2CC1 LVGUHWADRXKKTN-MRXNPFEDSA-N 0.000 claims description 2
• VIXLFZWEFXGIRZ-LJQANCHMSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-5-[4-(pyrrolidine-1-carbonyl)phenyl]-3h-isoindol-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)N3CCCC3)C=C2C1 VIXLFZWEFXGIRZ-LJQANCHMSA-N 0.000 claims description 2
• DYWLJRPIZPWGET-QGZVFWFLSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-(1-oxo-3,4-dihydro-2h-isoquinolin-6-yl)-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=C4CCNC(=O)C4=CC=3)C=C2CC1 DYWLJRPIZPWGET-QGZVFWFLSA-N 0.000 claims description 2
• DOZZMXWYOSFCSK-MRXNPFEDSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-(pyrrolidine-1-carbonyl)-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)N3CCCC3)C=C2CC1 DOZZMXWYOSFCSK-MRXNPFEDSA-N 0.000 claims description 2
• CGMNEQRSMXPAEO-HXUWFJFHSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-[4-(morpholine-4-carbonyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)N3CCOCC3)C=C2CC1 CGMNEQRSMXPAEO-HXUWFJFHSA-N 0.000 claims description 2
• RWVLKSWAEQZIHC-OAQYLSRUSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-[4-(piperidine-1-carbonyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)N3CCCCC3)C=C2CC1 RWVLKSWAEQZIHC-OAQYLSRUSA-N 0.000 claims description 2
• XPZHIEBBPQVJCT-HXUWFJFHSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-[4-(pyrrolidine-1-carbonyl)phenoxy]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(OC=3C=CC(=CC=3)C(=O)N3CCCC3)C=C2CC1 XPZHIEBBPQVJCT-HXUWFJFHSA-N 0.000 claims description 2
• SPKOQCHHYOCMGR-HXUWFJFHSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-[4-(pyrrolidine-1-carbonyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)N3CCCC3)C=C2CC1 SPKOQCHHYOCMGR-HXUWFJFHSA-N 0.000 claims description 2
• OCEASSQDJLNZSQ-QGZVFWFLSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-piperidin-1-yl-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(N3CCCCC3)C=C2CC1 OCEASSQDJLNZSQ-QGZVFWFLSA-N 0.000 claims description 2
• BCFUWSDYWOXETI-MRXNPFEDSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-pyrrolidin-1-yl-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(N3CCCC3)C=C2CC1 BCFUWSDYWOXETI-MRXNPFEDSA-N 0.000 claims description 2
• HJYQEGBJLDVMGC-HXUWFJFHSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-7-[4-(pyrrolidine-1-carbonyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC(C=3C=CC(=CC=3)C(=O)N3CCCC3)=CC=C2CC1 HJYQEGBJLDVMGC-HXUWFJFHSA-N 0.000 claims description 2
• RJJREVXLBPEJNJ-UHFFFAOYSA-N 2-methyl-6-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C2C(=O)N(C)CCC2=CC=1C(C=C1CC2)=CC=C1C(=O)N2CCN1CCCC1 RJJREVXLBPEJNJ-UHFFFAOYSA-N 0.000 claims description 2
• PPMUILQUJWTJIP-GOSISDBHSA-N 2-methyl-6-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=C4CCN(C)C(=O)C4=CC=3)C=C2CC1 PPMUILQUJWTJIP-GOSISDBHSA-N 0.000 claims description 2
• GAWGFYBLRGTQOO-UHFFFAOYSA-N 3-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzonitrile Chemical compound C1CC2=CC(C=3C=C(C=CC=3)C#N)=CC=C2C(=O)N1CCN1CCCC1 GAWGFYBLRGTQOO-UHFFFAOYSA-N 0.000 claims description 2
• OQCHJTQVESQEMN-UHFFFAOYSA-N 3-[1-oxo-2-(3-pyrrolidin-1-ylpropyl)-3,4-dihydroisoquinolin-6-yl]benzonitrile Chemical compound C1CC2=CC(C=3C=C(C=CC=3)C#N)=CC=C2C(=O)N1CCCN1CCCC1 OQCHJTQVESQEMN-UHFFFAOYSA-N 0.000 claims description 2
• NPJBTLMUZORITB-QGZVFWFLSA-N 3-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-5-yl]benzonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C(C=CC=C2C=3C=C(C=CC=3)C#N)=C2CC1 NPJBTLMUZORITB-QGZVFWFLSA-N 0.000 claims description 2
• UQIRATJNZOMMRO-UHFFFAOYSA-N 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzonitrile Chemical compound C1CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2C(=O)N1CCN1CCCC1 UQIRATJNZOMMRO-UHFFFAOYSA-N 0.000 claims description 2
• DHFMLRJPFZHXON-UHFFFAOYSA-N 4-[1-oxo-2-(3-piperidin-1-ylpropyl)-3,4-dihydroisoquinolin-6-yl]benzonitrile Chemical compound C1CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2C(=O)N1CCCN1CCCCC1 DHFMLRJPFZHXON-UHFFFAOYSA-N 0.000 claims description 2
• XVSGKDREUJXSJI-UHFFFAOYSA-N 4-[1-oxo-2-(3-pyrrolidin-1-ylpropyl)-3,4-dihydroisoquinolin-6-yl]benzonitrile Chemical compound C1CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2C(=O)N1CCCN1CCCC1 XVSGKDREUJXSJI-UHFFFAOYSA-N 0.000 claims description 2
• GEKDFQFAAHBUSW-QGZVFWFLSA-N 4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-5-yl]benzonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C(C=CC=C2C=3C=CC(=CC=3)C#N)=C2CC1 GEKDFQFAAHBUSW-QGZVFWFLSA-N 0.000 claims description 2
• TXFFWCPTQAOPNJ-QGZVFWFLSA-N 4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C#N)C=C2CC1 TXFFWCPTQAOPNJ-QGZVFWFLSA-N 0.000 claims description 2
• RBKYCZCNVBZBJX-QGZVFWFLSA-N 4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-7-yl]benzonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC(C=3C=CC(=CC=3)C#N)=CC=C2CC1 RBKYCZCNVBZBJX-QGZVFWFLSA-N 0.000 claims description 2
• VKDSWJFAIIVEQX-MRXNPFEDSA-N 4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3h-isoindol-5-yl]benzonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C#N)C=C2C1 VKDSWJFAIIVEQX-MRXNPFEDSA-N 0.000 claims description 2
• TXFFWCPTQAOPNJ-KRWDZBQOSA-N 4-[2-[2-[(2s)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzonitrile Chemical compound C[C@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C#N)C=C2CC1 TXFFWCPTQAOPNJ-KRWDZBQOSA-N 0.000 claims description 2
• DKFXEXRXJSDLGU-UHFFFAOYSA-N 4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 DKFXEXRXJSDLGU-UHFFFAOYSA-N 0.000 claims description 2
• WEAMNIVNLBZRJQ-UHFFFAOYSA-N 4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzonitrile Chemical compound C1CC2=CC(OC=3C=CC(=CC=3)C#N)=CC=C2C(=O)N1CCN1CCCC1 WEAMNIVNLBZRJQ-UHFFFAOYSA-N 0.000 claims description 2
• JFKJRURGYVFQQJ-QGZVFWFLSA-N 4-[[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]oxy]benzonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(OC=3C=CC(=CC=3)C#N)C=C2CC1 JFKJRURGYVFQQJ-QGZVFWFLSA-N 0.000 claims description 2
• NEOVUCPJBUHDMO-GOSISDBHSA-N 4-[[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]oxymethyl]benzonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(OCC=3C=CC(=CC=3)C#N)C=C2CC1 NEOVUCPJBUHDMO-GOSISDBHSA-N 0.000 claims description 2
• XVVITBZYEYKSAH-UHFFFAOYSA-N 5-(benzimidazol-1-ylmethyl)-2-(2-pyrrolidin-1-ylethyl)-3h-isoindol-1-one Chemical compound C1C2=CC(CN3C4=CC=CC=C4N=C3)=CC=C2C(=O)N1CCN1CCCC1 XVVITBZYEYKSAH-UHFFFAOYSA-N 0.000 claims description 2
• HUHFBMZFDZXFIC-MRXNPFEDSA-N 5-[[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]oxy]pyridine-2-carbonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(OC=3C=NC(=CC=3)C#N)C=C2CC1 HUHFBMZFDZXFIC-MRXNPFEDSA-N 0.000 claims description 2
• HTEJXYYZEOUJDH-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinoline Chemical compound C1CC2=CC(C=3C=C4OCOC4=CC=3)=CC=C2CN1CCN1CCCC1 HTEJXYYZEOUJDH-UHFFFAOYSA-N 0.000 claims description 2
• IMZFMNPADUBNHA-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(C=3C=C4OCOC4=CC=3)=CC=C2C(=O)N1CCN1CCCC1 IMZFMNPADUBNHA-UHFFFAOYSA-N 0.000 claims description 2
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• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical group CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 1
• GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
• 229910052722 tritium Chemical group 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1
• 230000003936 working memory Effects 0.000 description 1