CA2699384A1 - Isoquinolinyl and isoindolinyl derivatives as histamine-3 antagonists - Google Patents
Isoquinolinyl and isoindolinyl derivatives as histamine-3 antagonists Download PDFInfo
- Publication number
- CA2699384A1 CA2699384A1 CA2699384A CA2699384A CA2699384A1 CA 2699384 A1 CA2699384 A1 CA 2699384A1 CA 2699384 A CA2699384 A CA 2699384A CA 2699384 A CA2699384 A CA 2699384A CA 2699384 A1 CA2699384 A1 CA 2699384A1
- Authority
- CA
- Canada
- Prior art keywords
- pyrrolidin
- ylethyl
- oxo
- ethyl
- tetrahydroisoquinolin
- Prior art date
- 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
- 239000005557 antagonist Substances 0.000 title description 9
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 title description 3
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 240
- 238000011282 treatment Methods 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims description 103
- 238000002360 preparation method Methods 0.000 claims description 76
- -1 cycloheteroalkyl Chemical group 0.000 claims description 68
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 65
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 38
- 208000010877 cognitive disease Diseases 0.000 claims description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 25
- 208000024827 Alzheimer disease Diseases 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 21
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 19
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 18
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 18
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 201000000980 schizophrenia Diseases 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 206010012289 Dementia Diseases 0.000 claims description 14
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 208000018737 Parkinson disease Diseases 0.000 claims description 10
- 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
- 239000002904 solvent Substances 0.000 claims description 9
- 208000023105 Huntington disease Diseases 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 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
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 230000006870 function Effects 0.000 claims description 7
- 208000028017 Psychotic disease Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 201000004810 Vascular dementia Diseases 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 208000031091 Amnestic disease Diseases 0.000 claims description 4
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 208000012239 Developmental disease Diseases 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 230000006999 cognitive decline Effects 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 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 3
- 150000005072 1,3,4-oxadiazoles Chemical class 0.000 claims description 3
- 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 3
- 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 3
- 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 3
- PESOUNLSPHQJGL-INIZCTEOSA-N 6-(4-fluorophenyl)-2-[2-[(2s)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(F)=CC=3)C=C2CC1 PESOUNLSPHQJGL-INIZCTEOSA-N 0.000 claims description 3
- BXBHVUTUDLRKMI-UHFFFAOYSA-N 6-(pyrrolidine-1-carbonyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C2C(=O)N(CCN3CCCC3)CCC2=CC=1C(=O)N1CCCC1 BXBHVUTUDLRKMI-UHFFFAOYSA-N 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
- 208000001914 Fragile X 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
- 206010033864 Paranoia Diseases 0.000 claims description 3
- 208000027099 Paranoid disease Diseases 0.000 claims description 3
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 206010044688 Trisomy 21 Diseases 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
- ZOYRJBIULHDHMS-UHFFFAOYSA-N n-methoxy-n-methyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N(C)OC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 ZOYRJBIULHDHMS-UHFFFAOYSA-N 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 230000009529 traumatic brain injury Effects 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
- VCCZQTCRRYEOMQ-UHFFFAOYSA-N 2-[2-(azepan-1-yl)ethyl]-6-(4-fluorophenyl)-3,4-dihydro-1h-isoquinoline Chemical compound C1=CC(F)=CC=C1C1=CC=C(CN(CCN2CCCCCC2)CC2)C2=C1 VCCZQTCRRYEOMQ-UHFFFAOYSA-N 0.000 claims description 2
- LHOPPDSAKXYMGM-UHFFFAOYSA-N 2-[2-(azepan-1-yl)ethyl]-6-piperidin-1-yl-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N3CCCCC3)=CC=C2C(=O)N1CCN1CCCCCC1 LHOPPDSAKXYMGM-UHFFFAOYSA-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
- XNIIGFMTISXHOP-QGZVFWFLSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-6-(piperidine-1-carbonyl)-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)N3CCCCC3)C=C2CC1 XNIIGFMTISXHOP-QGZVFWFLSA-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
- 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
- MJWFELMHVFWAFR-UHFFFAOYSA-N 2-fluoro-n,n-dimethyl-5-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=C(F)C(C(=O)N(C)C)=CC(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)=C1 MJWFELMHVFWAFR-UHFFFAOYSA-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
- 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
- LKAIVZUDLWBTPK-UHFFFAOYSA-N 3-fluoro-n,n-dimethyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound FC1=CC(C(=O)N(C)C)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 LKAIVZUDLWBTPK-UHFFFAOYSA-N 0.000 claims description 2
- YCVSODHAECQRSZ-UHFFFAOYSA-N 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]-n-(1,3-thiazol-2-yl)benzamide Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NC1=NC=CS1 YCVSODHAECQRSZ-UHFFFAOYSA-N 0.000 claims description 2
- OHGCBLVQNCOGMT-UHFFFAOYSA-N 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]-n-(2-phenoxyethyl)benzamide Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NCCOC1=CC=CC=C1 OHGCBLVQNCOGMT-UHFFFAOYSA-N 0.000 claims description 2
- ABPXUDPIMPCFSO-UHFFFAOYSA-N 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]-n-(2-propan-2-yloxyethyl)benzamide Chemical compound C1=CC(C(=O)NCCOC(C)C)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 ABPXUDPIMPCFSO-UHFFFAOYSA-N 0.000 claims description 2
- HWXMHTGXJYCLRE-UHFFFAOYSA-N 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]-n-(thiophen-2-ylmethyl)benzamide Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NCC1=CC=CS1 HWXMHTGXJYCLRE-UHFFFAOYSA-N 0.000 claims description 2
- WJWTXHWEEDAGPF-UHFFFAOYSA-N 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]-n-propylbenzamide Chemical compound C1=CC(C(=O)NCCC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 WJWTXHWEEDAGPF-UHFFFAOYSA-N 0.000 claims description 2
- CCHLSEPSYHUUJN-UHFFFAOYSA-N 4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 CCHLSEPSYHUUJN-UHFFFAOYSA-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
- 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
- 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
- VSWIQVCFSZZKDR-UHFFFAOYSA-N 5-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]pyridine-2-carbonitrile Chemical compound C1CC2=CC(OC=3C=NC(=CC=3)C#N)=CC=C2C(=O)N1CCN1CCCC1 VSWIQVCFSZZKDR-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
- DVTQVYYIBAQMQE-GOSISDBHSA-N 6-(1,3-dihydroisoindole-2-carbonyl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)N3CC4=CC=CC=C4C3)C=C2CC1 DVTQVYYIBAQMQE-GOSISDBHSA-N 0.000 claims description 2
- LOXZVEKDMPWGAL-UHFFFAOYSA-N 6-(2-fluorophenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound FC1=CC=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 LOXZVEKDMPWGAL-UHFFFAOYSA-N 0.000 claims description 2
- GYCYFTUXIPKESF-UHFFFAOYSA-N 6-(3,4-difluorophenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1=C(F)C(F)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 GYCYFTUXIPKESF-UHFFFAOYSA-N 0.000 claims description 2
- XFUIQLKOBHTVHP-LJQANCHMSA-N 6-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)N3CC4=CC=CC=C4CC3)C=C2CC1 XFUIQLKOBHTVHP-LJQANCHMSA-N 0.000 claims description 2
- VYWPYDHJBNEPBP-UHFFFAOYSA-N 6-(3,5-difluorophenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound FC1=CC(F)=CC(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)=C1 VYWPYDHJBNEPBP-UHFFFAOYSA-N 0.000 claims description 2
- UNHZLQRDVHLVSK-UHFFFAOYSA-N 6-(3-fluorophenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinoline Chemical compound FC1=CC=CC(C=2C=C3CCN(CCN4CCCC4)CC3=CC=2)=C1 UNHZLQRDVHLVSK-UHFFFAOYSA-N 0.000 claims description 2
- WLSIIBHMNYNDNS-UHFFFAOYSA-N 6-(3-fluorophenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound FC1=CC=CC(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)=C1 WLSIIBHMNYNDNS-UHFFFAOYSA-N 0.000 claims description 2
- ZDFCXWNFABFQEW-UHFFFAOYSA-N 6-(4-fluorophenyl)-2-(2-piperidin-1-ylethyl)-3,4-dihydro-1h-isoquinoline Chemical compound C1=CC(F)=CC=C1C1=CC=C(CN(CCN2CCCCC2)CC2)C2=C1 ZDFCXWNFABFQEW-UHFFFAOYSA-N 0.000 claims description 2
- GHRKTWSYAPPZEP-UHFFFAOYSA-N 6-(4-fluorophenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(F)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 GHRKTWSYAPPZEP-UHFFFAOYSA-N 0.000 claims description 2
- DIQPFOSOOFNUQW-UHFFFAOYSA-N 6-(4-methoxyphenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 DIQPFOSOOFNUQW-UHFFFAOYSA-N 0.000 claims description 2
- VKZKSELGBRDDRN-UHFFFAOYSA-N 6-(4-methylsulfonylphenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 VKZKSELGBRDDRN-UHFFFAOYSA-N 0.000 claims description 2
- BTHDBDIXZQYFMB-UHFFFAOYSA-N 6-(benzimidazol-1-yl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N3C4=CC=CC=C4N=C3)=CC=C2C(=O)N1CCN1CCCC1 BTHDBDIXZQYFMB-UHFFFAOYSA-N 0.000 claims description 2
- QZGVPLQPUBNUMV-UHFFFAOYSA-N 6-(piperidine-1-carbonyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C2C(=O)N(CCN3CCCC3)CCC2=CC=1C(=O)N1CCCCC1 QZGVPLQPUBNUMV-UHFFFAOYSA-N 0.000 claims description 2
- MEWSMJAOOPXCMF-UHFFFAOYSA-N 6-[2-fluoro-4-(pyrrolidine-1-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound FC1=CC(C(=O)N2CCCC2)=CC=C1C(C=C1CC2)=CC=C1C(=O)N2CCN1CCCC1 MEWSMJAOOPXCMF-UHFFFAOYSA-N 0.000 claims description 2
- TYGMGAZPXWLANI-UHFFFAOYSA-N 6-[3-chloro-4-(pyrrolidine-1-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound ClC1=CC(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)=CC=C1C(=O)N1CCCC1 TYGMGAZPXWLANI-UHFFFAOYSA-N 0.000 claims description 2
- PSOYZSZZNCJMRX-UHFFFAOYSA-N 6-[3-fluoro-4-(pyrrolidine-1-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound FC1=CC(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)=CC=C1C(=O)N1CCCC1 PSOYZSZZNCJMRX-UHFFFAOYSA-N 0.000 claims description 2
- AVXJIYHIOLMDHB-UHFFFAOYSA-N 6-[4-(3-methoxypyrrolidine-1-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1C(OC)CCN1C(=O)C1=CC=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=C1 AVXJIYHIOLMDHB-UHFFFAOYSA-N 0.000 claims description 2
- ZZWWPCHANMIGSS-UHFFFAOYSA-N 6-[4-(azetidine-1-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)N1CCC1 ZZWWPCHANMIGSS-UHFFFAOYSA-N 0.000 claims description 2
- SOGOTVMZEUKLOJ-UHFFFAOYSA-N 6-[4-(morpholine-4-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)N1CCOCC1 SOGOTVMZEUKLOJ-UHFFFAOYSA-N 0.000 claims description 2
- RBZZHYUAZBYTMD-UHFFFAOYSA-N 6-[4-(pyrrolidine-1-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)N1CCCC1 RBZZHYUAZBYTMD-UHFFFAOYSA-N 0.000 claims description 2
- HLTWIRAJTFHHKP-VWLOTQADSA-N 6-[4-[(2s)-2-(methoxymethyl)pyrrolidine-1-carbonyl]phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound COC[C@@H]1CCCN1C(=O)C1=CC=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=C1 HLTWIRAJTFHHKP-VWLOTQADSA-N 0.000 claims description 2
- QKNQLRSRULGFBA-FQEVSTJZSA-N 6-[4-[(2s)-2-methylpyrrolidine-1-carbonyl]phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C[C@H]1CCCN1C(=O)C1=CC=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=C1 QKNQLRSRULGFBA-FQEVSTJZSA-N 0.000 claims description 2
- FNNSZXVZZPJSLH-UHFFFAOYSA-N 6-[4-fluoro-3-(pyrrolidine-1-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound FC1=CC=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=C1C(=O)N1CCCC1 FNNSZXVZZPJSLH-UHFFFAOYSA-N 0.000 claims description 2
- WJSMRXZBXLZTEH-UHFFFAOYSA-N 6-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]pyridine-3-carbonitrile Chemical compound C1CC2=CC(OC=3N=CC(=CC=3)C#N)=CC=C2C(=O)N1CCN1CCCC1 WJSMRXZBXLZTEH-UHFFFAOYSA-N 0.000 claims description 2
- VCQCSXTXOSODCY-MRXNPFEDSA-N 6-[[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]oxy]pyridine-3-carbonitrile Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(OC=3N=CC(=CC=3)C#N)C=C2CC1 VCQCSXTXOSODCY-MRXNPFEDSA-N 0.000 claims description 2
- GSAGTJUQXZNCBN-UHFFFAOYSA-N 6-phenyl-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(C=3C=CC=CC=3)=CC=C2C(=O)N1CCN1CCCC1 GSAGTJUQXZNCBN-UHFFFAOYSA-N 0.000 claims description 2
- WNHAEBNVEXIILO-UHFFFAOYSA-N 6-piperidin-1-yl-2-(2-piperidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N3CCCCC3)=CC=C2C(=O)N1CCN1CCCCC1 WNHAEBNVEXIILO-UHFFFAOYSA-N 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- DLTVEUZATGGLPH-NRFANRHFSA-N [(2s)-2-methylpyrrolidin-1-yl]-[4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]phenyl]methanone Chemical compound C[C@H]1CCCN1C(=O)C1=CC=C(C=2C=C3CCN(CCN4CCCC4)CC3=CC=2)C=C1 DLTVEUZATGGLPH-NRFANRHFSA-N 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims description 2
- VYLIMHRUIYQQGO-UHFFFAOYSA-N n,n-dimethyl-4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1OC1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 VYLIMHRUIYQQGO-UHFFFAOYSA-N 0.000 claims description 2
- FHYNFBTXKRBYQL-GOSISDBHSA-N n-(2,3-dihydro-1h-inden-2-yl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinoline-6-carboxamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)NC3CC4=CC=CC=C4C3)C=C2CC1 FHYNFBTXKRBYQL-GOSISDBHSA-N 0.000 claims description 2
- ZEIHGCBVHBPLFU-UHFFFAOYSA-N n-(2-chloroethyl)-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NCCCl)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 ZEIHGCBVHBPLFU-UHFFFAOYSA-N 0.000 claims description 2
- BMMRYMVMQGKMNM-UHFFFAOYSA-N n-(2-ethoxyethyl)-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NCCOCC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 BMMRYMVMQGKMNM-UHFFFAOYSA-N 0.000 claims description 2
- UVUAABURRDZMTP-GOSISDBHSA-N n-(2-fluoroethyl)-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)NCCF)C=C2CC1 UVUAABURRDZMTP-GOSISDBHSA-N 0.000 claims description 2
- FHPFAGGYLXCTQY-UHFFFAOYSA-N n-(2-methoxyethyl)-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NCCOC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 FHPFAGGYLXCTQY-UHFFFAOYSA-N 0.000 claims description 2
- WYMBHGMKRJYHMY-UHFFFAOYSA-N n-(furan-2-ylmethyl)-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NCC1=CC=CO1 WYMBHGMKRJYHMY-UHFFFAOYSA-N 0.000 claims description 2
- NURAFFFLJXNEDY-IBGZPJMESA-N n-[(2s)-1-methoxypropan-2-yl]-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N[C@@H](C)COC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 NURAFFFLJXNEDY-IBGZPJMESA-N 0.000 claims description 2
- WGLUNLJVYNJMBU-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[(3-methyl-1-oxo-2,4-dihydroisoquinolin-3-yl)methyl]decanamide Chemical compound C1=CC=C2C(=O)NC(CN(CCN(C)C)C(=O)CCCCCCCCC)(C)CC2=C1 WGLUNLJVYNJMBU-UHFFFAOYSA-N 0.000 claims description 2
- LLGQUVDAYOKISQ-UHFFFAOYSA-N n-cyclobutyl-4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzamide Chemical compound C=1C=C(OC=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NC1CCC1 LLGQUVDAYOKISQ-UHFFFAOYSA-N 0.000 claims description 2
- WZHAQWFZACLGKI-UHFFFAOYSA-N n-cyclopentyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NC1CCCC1 WZHAQWFZACLGKI-UHFFFAOYSA-N 0.000 claims description 2
- ZRPZQWYLPYZTMX-UHFFFAOYSA-N n-cyclopropyl-4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzamide Chemical compound C=1C=C(OC=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NC1CC1 ZRPZQWYLPYZTMX-UHFFFAOYSA-N 0.000 claims description 2
- MQSLEZBBFIFABX-UHFFFAOYSA-N n-ethyl-3-fluoro-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound FC1=CC(C(=O)NCC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 MQSLEZBBFIFABX-UHFFFAOYSA-N 0.000 claims description 2
- QAXSLEDHLDQAFD-UHFFFAOYSA-N n-ethyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NCC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 QAXSLEDHLDQAFD-UHFFFAOYSA-N 0.000 claims description 2
- CEAMWQXBGHROCC-UHFFFAOYSA-N n-ethyl-4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NCC)=CC=C1C1=CC=C(CN(CCN2CCCC2)CC2)C2=C1 CEAMWQXBGHROCC-UHFFFAOYSA-N 0.000 claims description 2
- HRUBNPOSYONRAN-UHFFFAOYSA-N n-ethyl-n-methyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N(C)CC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 HRUBNPOSYONRAN-UHFFFAOYSA-N 0.000 claims description 2
- YPBPMHNGMUTNFM-UHFFFAOYSA-N n-methyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 YPBPMHNGMUTNFM-UHFFFAOYSA-N 0.000 claims description 2
- ALCJQUUDYHPXHV-MRXNPFEDSA-N n-methyl-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3h-isoindol-5-yl]benzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)C2)C2=C1 ALCJQUUDYHPXHV-MRXNPFEDSA-N 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- WKAXMZCFRUWWKL-UHFFFAOYSA-N piperidin-1-yl-[4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]phenyl]methanone Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)CC3=CC=2)C=CC=1C(=O)N1CCCCC1 WKAXMZCFRUWWKL-UHFFFAOYSA-N 0.000 claims description 2
- JIDHIDSOIJOIKM-UHFFFAOYSA-N pyrrolidin-1-yl-[4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]phenyl]methanone Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)CC3=CC=2)C=CC=1C(=O)N1CCCC1 JIDHIDSOIJOIKM-UHFFFAOYSA-N 0.000 claims description 2
- 230000002123 temporal effect Effects 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 1
- ULDQVOFOHYQSEB-UHFFFAOYSA-N 2-[2-(azepan-1-yl)ethyl]-6-(4-fluorophenyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(F)=CC=C1C1=CC=C(C(=O)N(CCN2CCCCCC2)CC2)C2=C1 ULDQVOFOHYQSEB-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- DABFIICBZLUPJU-UHFFFAOYSA-N 3-fluoro-n-methyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound FC1=CC(C(=O)NC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 DABFIICBZLUPJU-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- KLCMNSIUSBEXGI-UHFFFAOYSA-N 4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC=C(CN(CCN2CCCC2)CC2)C2=C1 KLCMNSIUSBEXGI-UHFFFAOYSA-N 0.000 claims 1
- OGCKPACJJOYWEA-OAQYLSRUSA-N 4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]-n-(2-propan-2-yloxyethyl)benzamide Chemical compound C1=CC(C(=O)NCCOC(C)C)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 OGCKPACJJOYWEA-OAQYLSRUSA-N 0.000 claims 1
- LQUHPXJXWPFZKI-LJQANCHMSA-N 4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]-n-propan-2-ylbenzamide Chemical compound C1=CC(C(=O)NC(C)C)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 LQUHPXJXWPFZKI-LJQANCHMSA-N 0.000 claims 1
- CNFSSMVBGNBSDR-UHFFFAOYSA-N 4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1OC1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 CNFSSMVBGNBSDR-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- WCDNIALSRDXDEO-UHFFFAOYSA-N 6-(1,3-dihydroisoindole-2-carbonyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1C2=CC=CC=C2CN1C(=O)C(C=C1CC2)=CC=C1C(=O)N2CCN1CCCC1 WCDNIALSRDXDEO-UHFFFAOYSA-N 0.000 claims 1
- GIHJOOARQXFDOP-UHFFFAOYSA-N 6-(2,4-difluorophenyl)-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound FC1=CC(F)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 GIHJOOARQXFDOP-UHFFFAOYSA-N 0.000 claims 1
- PESOUNLSPHQJGL-MRXNPFEDSA-N 6-(4-fluorophenyl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(F)=CC=3)C=C2CC1 PESOUNLSPHQJGL-MRXNPFEDSA-N 0.000 claims 1
- BPNWHQZDCCBREC-GOSISDBHSA-N 6-(azepan-1-yl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(N3CCCCCC3)C=C2CC1 BPNWHQZDCCBREC-GOSISDBHSA-N 0.000 claims 1
- YXVYVEQLGFEDLP-LJQANCHMSA-N 6-[4-(azetidine-1-carbonyl)phenyl]-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)N3CCC3)C=C2CC1 YXVYVEQLGFEDLP-LJQANCHMSA-N 0.000 claims 1
- IXGOGVFDYFVFOF-UHFFFAOYSA-N 6-[4-(cyclopropanecarbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)C1CC1 IXGOGVFDYFVFOF-UHFFFAOYSA-N 0.000 claims 1
- FTJQBQMPWIVAQU-UHFFFAOYSA-N 6-[4-(piperidine-1-carbonyl)phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)N1CCCCC1 FTJQBQMPWIVAQU-UHFFFAOYSA-N 0.000 claims 1
- QKNQLRSRULGFBA-HXUWFJFHSA-N 6-[4-[(2r)-2-methylpyrrolidine-1-carbonyl]phenyl]-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1C(=O)C1=CC=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=C1 QKNQLRSRULGFBA-HXUWFJFHSA-N 0.000 claims 1
- BTIBJMKJNQUNFA-RLWLMLJZSA-N 6-[4-[(2s)-2-(methoxymethyl)pyrrolidine-1-carbonyl]phenyl]-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound COC[C@@H]1CCCN1C(=O)C1=CC=C(C=2C=C3CCN(CCN4[C@@H](CCC4)C)C(=O)C3=CC=2)C=C1 BTIBJMKJNQUNFA-RLWLMLJZSA-N 0.000 claims 1
- IWUGHHQMBCOMOV-UHFFFAOYSA-N 6-indazol-1-yl-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N3C4=CC=CC=C4C=N3)=CC=C2C(=O)N1CCN1CCCC1 IWUGHHQMBCOMOV-UHFFFAOYSA-N 0.000 claims 1
- LHTGPDWLAXLFNE-UHFFFAOYSA-N 6-piperidin-1-yl-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N3CCCCC3)=CC=C2C(=O)N1CCN1CCCC1 LHTGPDWLAXLFNE-UHFFFAOYSA-N 0.000 claims 1
- LXRHFSAOTQKITL-UHFFFAOYSA-N 6-pyrazol-1-yl-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N3N=CC=C3)=CC=C2C(=O)N1CCN1CCCC1 LXRHFSAOTQKITL-UHFFFAOYSA-N 0.000 claims 1
- OYOUUSCAVHSQKA-UHFFFAOYSA-N 6-pyridin-4-yl-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(C=3C=CN=CC=3)=CC=C2C(=O)N1CCN1CCCC1 OYOUUSCAVHSQKA-UHFFFAOYSA-N 0.000 claims 1
- OLPBBMNEBRGWCP-UHFFFAOYSA-N N-methyl-4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzamide 4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzamide Chemical compound CNC(C1=CC=C(C=C1)OC=1C=C2CCN(C(C2=CC1)=O)CCN1CCCC1)=O.O=C1N(CCC2=CC(=CC=C12)OC1=CC=C(C(=O)N)C=C1)CCN1CCCC1 OLPBBMNEBRGWCP-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- ABAUQRQEOVFAGR-UHFFFAOYSA-N morpholin-4-yl-[4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]phenyl]methanone Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)CC3=CC=2)C=CC=1C(=O)N1CCOCC1 ABAUQRQEOVFAGR-UHFFFAOYSA-N 0.000 claims 1
- LIFZQJWSMAVMKN-HXUWFJFHSA-N n,n-diethyl-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 LIFZQJWSMAVMKN-HXUWFJFHSA-N 0.000 claims 1
- FRGXBLUHPWIROA-UHFFFAOYSA-N n,n-dimethyl-4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C1=CC=C(CN(CCN2CCCC2)CC2)C2=C1 FRGXBLUHPWIROA-UHFFFAOYSA-N 0.000 claims 1
- WCAKVWZDJOPNBF-UHFFFAOYSA-N n-(2-fluoroethyl)-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NCCF)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 WCAKVWZDJOPNBF-UHFFFAOYSA-N 0.000 claims 1
- HARMHPCFBYXGJW-LJQANCHMSA-N n-(2-methoxyethyl)-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NCCOC)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 HARMHPCFBYXGJW-LJQANCHMSA-N 0.000 claims 1
- NMNCZBWJSIBKFH-LJQANCHMSA-N n-(cyclopropylmethyl)-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)NCC3CC3)C=C2CC1 NMNCZBWJSIBKFH-LJQANCHMSA-N 0.000 claims 1
- VEVKQFLTUGUGSG-VQTJNVASSA-N n-[(2s)-1-methoxypropan-2-yl]-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N[C@@H](C)COC)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 VEVKQFLTUGUGSG-VQTJNVASSA-N 0.000 claims 1
- AYQFYLUEXSWBBJ-LJQANCHMSA-N n-cyclobutyl-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)NC3CCC3)C=C2CC1 AYQFYLUEXSWBBJ-LJQANCHMSA-N 0.000 claims 1
- ROKUNGAJIWRDNO-HXUWFJFHSA-N n-cyclopentyl-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)NC3CCCC3)C=C2CC1 ROKUNGAJIWRDNO-HXUWFJFHSA-N 0.000 claims 1
- IOZOVXCLYGPBKD-UHFFFAOYSA-N n-cyclopropyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NC1CC1 IOZOVXCLYGPBKD-UHFFFAOYSA-N 0.000 claims 1
- HUTSKAWLZWARNV-GOSISDBHSA-N n-cyclopropyl-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(=O)NC3CC3)C=C2CC1 HUTSKAWLZWARNV-GOSISDBHSA-N 0.000 claims 1
- LBAKRWRQQGNMEB-GOSISDBHSA-N n-ethyl-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NCC)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 LBAKRWRQQGNMEB-GOSISDBHSA-N 0.000 claims 1
- UMHKDLZBMOFQMY-UHFFFAOYSA-N n-ethyl-4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzamide Chemical compound C1=CC(C(=O)NCC)=CC=C1OC1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 UMHKDLZBMOFQMY-UHFFFAOYSA-N 0.000 claims 1
- NAJDEFVMRKZNHZ-LJQANCHMSA-N n-ethyl-n-methyl-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N(C)CC)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 NAJDEFVMRKZNHZ-LJQANCHMSA-N 0.000 claims 1
- QJYYNDZFNAOIKS-UHFFFAOYSA-N n-methyl-4-[1-oxo-2-(3-pyrrolidin-1-ylpropyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=CC=C(C(=O)N(CCCN2CCCC2)CC2)C2=C1 QJYYNDZFNAOIKS-UHFFFAOYSA-N 0.000 claims 1
- BGTBUIVWRSIAAN-UHFFFAOYSA-N n-methyl-4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=CC=C(CN(CCN2CCCC2)CC2)C2=C1 BGTBUIVWRSIAAN-UHFFFAOYSA-N 0.000 claims 1
- CNMAKXCQNYZOPH-QGZVFWFLSA-N n-methyl-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 CNMAKXCQNYZOPH-QGZVFWFLSA-N 0.000 claims 1
- DRMXLXBOGFENHJ-UHFFFAOYSA-N n-methyl-6-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]pyridine-3-carboxamide Chemical compound N1=CC(C(=O)NC)=CC=C1OC1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 DRMXLXBOGFENHJ-UHFFFAOYSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 208000015114 central nervous system disease Diseases 0.000 abstract description 7
- 208000012902 Nervous system disease Diseases 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 234
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 120
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 86
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 77
- 239000000243 solution Substances 0.000 description 69
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- 239000007787 solid Substances 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 42
- 239000000377 silicon dioxide Substances 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 239000003921 oil Substances 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 235000019198 oils Nutrition 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 37
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
- 229910052938 sodium sulfate Inorganic materials 0.000 description 36
- 235000011152 sodium sulphate Nutrition 0.000 description 36
- 239000012230 colorless oil Substances 0.000 description 33
- 150000001412 amines Chemical class 0.000 description 32
- 238000004587 chromatography analysis Methods 0.000 description 32
- 239000000284 extract Substances 0.000 description 32
- 239000000203 mixture Substances 0.000 description 31
- 238000004458 analytical method Methods 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
- 239000007832 Na2SO4 Substances 0.000 description 28
- 239000006260 foam Substances 0.000 description 28
- 230000003595 spectral effect Effects 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- 229910000104 sodium hydride Inorganic materials 0.000 description 26
- 229910000027 potassium carbonate Inorganic materials 0.000 description 25
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 24
- 102000004384 Histamine H3 receptors Human genes 0.000 description 23
- 108090000981 Histamine H3 receptors Proteins 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- 235000019441 ethanol Nutrition 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 19
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 239000000908 ammonium hydroxide Substances 0.000 description 16
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 16
- 235000015320 potassium carbonate Nutrition 0.000 description 16
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical class CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 15
- 239000012065 filter cake Substances 0.000 description 15
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 15
- 239000007788 liquid Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 229910004373 HOAc Inorganic materials 0.000 description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
- 210000004556 brain Anatomy 0.000 description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 229960001340 histamine Drugs 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 239000005711 Benzoic acid Substances 0.000 description 8
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 8
- 235000010233 benzoic acid Nutrition 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 150000003840 hydrochlorides Chemical class 0.000 description 8
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
- NNNWZLIXJNOYPI-UHFFFAOYSA-N 6-bromo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(Br)=CC=C2C(=O)N1CCN1CCCC1 NNNWZLIXJNOYPI-UHFFFAOYSA-N 0.000 description 7
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 7
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 150000003951 lactams Chemical class 0.000 description 7
- 230000015654 memory Effects 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- FQPKKECSRKYXIZ-UHFFFAOYSA-N 6-bromo-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=CC(Br)=CC=C21 FQPKKECSRKYXIZ-UHFFFAOYSA-N 0.000 description 6
- 229910015845 BBr3 Inorganic materials 0.000 description 6
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- QKDDJDBFONZGBW-UHFFFAOYSA-N N-Cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide Chemical compound C1CC(C=2NC=NC=2)CCN1C(=S)NC1CCCCC1 QKDDJDBFONZGBW-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 230000019771 cognition Effects 0.000 description 6
- 230000006735 deficit Effects 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 6
- WXHIJDCHNDBCNY-UHFFFAOYSA-N palladium dihydride Chemical compound [PdH2] WXHIJDCHNDBCNY-UHFFFAOYSA-N 0.000 description 6
- 238000007911 parenteral administration Methods 0.000 description 6
- 239000002287 radioligand Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 208000019116 sleep disease Diseases 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 5
- RGHPCLZJAFCTIK-RXMQYKEDSA-N (R)-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1 RGHPCLZJAFCTIK-RXMQYKEDSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- BHNGUPIYNHVICC-UHFFFAOYSA-N 2-(5-bromo-1-oxo-3,4-dihydroisoquinolin-2-yl)acetaldehyde Chemical compound O=C1N(CC=O)CCC2=C1C=CC=C2Br BHNGUPIYNHVICC-UHFFFAOYSA-N 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- QBAAUIHPKOLVFD-UHFFFAOYSA-N 6-bromo-2-prop-2-enyl-3,4-dihydroisoquinolin-1-one Chemical compound O=C1N(CC=C)CCC2=CC(Br)=CC=C21 QBAAUIHPKOLVFD-UHFFFAOYSA-N 0.000 description 4
- STZXQWPZSSKZRV-UHFFFAOYSA-N 6-iodo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(I)=CC=C2C(=O)N1CCN1CCCC1 STZXQWPZSSKZRV-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 208000000044 Amnesia Diseases 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- 241000282326 Felis catus Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 150000001543 aryl boronic acids Chemical class 0.000 description 4
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 125000003636 chemical group Chemical group 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 239000002858 neurotransmitter agent Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229940044551 receptor antagonist Drugs 0.000 description 4
- 239000002464 receptor antagonist Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- JNEIFWYJFOEKIM-NUBCRITNSA-N (2r)-2-methylpyrrolidine;hydrochloride Chemical compound Cl.C[C@@H]1CCCN1 JNEIFWYJFOEKIM-NUBCRITNSA-N 0.000 description 3
- CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 3
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 3
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 3
- CFKTULOUAYCGEY-UHFFFAOYSA-N 2-(7-bromo-1-oxo-3,4-dihydroisoquinolin-2-yl)acetaldehyde Chemical compound C1CN(CC=O)C(=O)C2=CC(Br)=CC=C21 CFKTULOUAYCGEY-UHFFFAOYSA-N 0.000 description 3
- XUJGYVYCWSFUSE-UHFFFAOYSA-N 2-[6-(4-fluorophenyl)-1-oxo-3,4-dihydroisoquinolin-2-yl]acetaldehyde Chemical compound C1=CC(F)=CC=C1C1=CC=C(C(=O)N(CC=O)CC2)C2=C1 XUJGYVYCWSFUSE-UHFFFAOYSA-N 0.000 description 3
- LYXUIQHDUVHEMZ-UHFFFAOYSA-N 5-bromo-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=C1C=CC=C2Br LYXUIQHDUVHEMZ-UHFFFAOYSA-N 0.000 description 3
- PNZDKWGVPHBMRZ-UHFFFAOYSA-N 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C(=O)NCC2)C2=C1 PNZDKWGVPHBMRZ-UHFFFAOYSA-N 0.000 description 3
- RMXVHYPQXPHHGJ-UHFFFAOYSA-N 6-hydroxy-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(O)=CC=C2C(=O)N1CCN1CCCC1 RMXVHYPQXPHHGJ-UHFFFAOYSA-N 0.000 description 3
- TYNQFYSVGOMKOS-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=CC(O)=CC=C21 TYNQFYSVGOMKOS-UHFFFAOYSA-N 0.000 description 3
- JMMFTYDNMDAOQS-UHFFFAOYSA-N 6-methoxy-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(OC)=CC=C2C(=O)N1CCN1CCCC1 JMMFTYDNMDAOQS-UHFFFAOYSA-N 0.000 description 3
- VYSWAYIGKWKCDQ-CYBMUJFWSA-N 6-methoxy-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(OC)=CC=C2C(=O)N1CCN1CCC[C@H]1C VYSWAYIGKWKCDQ-CYBMUJFWSA-N 0.000 description 3
- DRDDOAWCDDBYHZ-UHFFFAOYSA-N 7-bromo-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1CNC(=O)C2=CC(Br)=CC=C21 DRDDOAWCDDBYHZ-UHFFFAOYSA-N 0.000 description 3
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 3
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 3
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000030814 Eating disease Diseases 0.000 description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 3
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 3
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
- 230000009102 absorption Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- 229940095074 cyclic amp Drugs 0.000 description 3
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- 235000014632 disordered eating Nutrition 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 239000003395 histamine H3 receptor antagonist Substances 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000013016 learning Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- VFRPLGSMZBWQBL-QGZVFWFLSA-N methyl 4-[[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]oxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 VFRPLGSMZBWQBL-QGZVFWFLSA-N 0.000 description 3
- CYEXEOXALMJXDI-UHFFFAOYSA-N methyl 4-bromo-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1C CYEXEOXALMJXDI-UHFFFAOYSA-N 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 208000021722 neuropathic pain Diseases 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 3
- 229960002646 scopolamine Drugs 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 3
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 2
- BKWRLCIYMAYFPA-UHFFFAOYSA-N (2-fluoro-4-methoxycarbonylphenyl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)C(F)=C1 BKWRLCIYMAYFPA-UHFFFAOYSA-N 0.000 description 2
- RGHPCLZJAFCTIK-YFKPBYRVSA-N (2s)-2-methylpyrrolidine Chemical compound C[C@H]1CCCN1 RGHPCLZJAFCTIK-YFKPBYRVSA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- VVPIREIVSFJKLA-UHFFFAOYSA-N 2-(6-bromo-1-oxo-3,4-dihydroisoquinolin-2-yl)acetaldehyde Chemical compound O=C1N(CC=O)CCC2=CC(Br)=CC=C21 VVPIREIVSFJKLA-UHFFFAOYSA-N 0.000 description 2
- XARIYCVQYCGKQI-UHFFFAOYSA-N 2-(6-fluoro-1-oxo-3,4-dihydroisoquinolin-2-yl)acetaldehyde Chemical compound O=C1N(CC=O)CCC2=CC(F)=CC=C21 XARIYCVQYCGKQI-UHFFFAOYSA-N 0.000 description 2
- IAEZKCYHPGSESD-UHFFFAOYSA-N 2-(6-methoxy-1-oxo-3,4-dihydroisoquinolin-2-yl)acetaldehyde Chemical compound O=C1N(CC=O)CCC2=CC(OC)=CC=C21 IAEZKCYHPGSESD-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- MQIMSKHNNLPTPK-CYBMUJFWSA-N 2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydro-1h-isoquinolin-6-ol Chemical compound C[C@@H]1CCCN1CCN1CC2=CC=C(O)C=C2CC1 MQIMSKHNNLPTPK-CYBMUJFWSA-N 0.000 description 2
- FURHRJBOFNDYTG-UHFFFAOYSA-N 2-fluoroethanamine Chemical compound NCCF FURHRJBOFNDYTG-UHFFFAOYSA-N 0.000 description 2
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
- USECIYVEPXUVHT-UHFFFAOYSA-N 2-propan-2-yloxyethanamine Chemical compound CC(C)OCCN USECIYVEPXUVHT-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 2
- GNDDWVVKZHDRTO-UHFFFAOYSA-N 4-[(1-oxo-3,4-dihydro-2h-isoquinolin-6-yl)oxymethyl]benzonitrile Chemical compound C=1C=C2C(=O)NCCC2=CC=1OCC1=CC=C(C#N)C=C1 GNDDWVVKZHDRTO-UHFFFAOYSA-N 0.000 description 2
- GAHGZCXEUANYIP-UHFFFAOYSA-N 4-[[1-oxo-2-(2-oxoethyl)-3,4-dihydroisoquinolin-6-yl]oxymethyl]benzonitrile Chemical compound C=1C=C2C(=O)N(CC=O)CCC2=CC=1OCC1=CC=C(C#N)C=C1 GAHGZCXEUANYIP-UHFFFAOYSA-N 0.000 description 2
- GQERSOMPIOODCF-MRXNPFEDSA-N 4-[[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]oxy]benzoic acid Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(OC=3C=CC(=CC=3)C(O)=O)C=C2CC1 GQERSOMPIOODCF-MRXNPFEDSA-N 0.000 description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 2
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 2
- XBZIXUFQVXJCGK-PKLMIRHRSA-N 5-(4-fluorophenyl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1,3-dihydroisoindole;hydrochloride Chemical compound Cl.C[C@@H]1CCCN1CCN1CC2=CC(C=3C=CC(F)=CC=3)=CC=C2C1 XBZIXUFQVXJCGK-PKLMIRHRSA-N 0.000 description 2
- MGZIBFGYOOKXCQ-OAHLLOKOSA-N 5-(4-fluorophenyl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3h-isoindol-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(F)=CC=3)C=C2C1 MGZIBFGYOOKXCQ-OAHLLOKOSA-N 0.000 description 2
- NPOMKDRCLYGLSY-UHFFFAOYSA-N 6-bromo-2-(3-piperidin-1-ylpropyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(Br)=CC=C2C(=O)N1CCCN1CCCCC1 NPOMKDRCLYGLSY-UHFFFAOYSA-N 0.000 description 2
- DQUIAHUPHBKSJV-UHFFFAOYSA-N 6-bromo-2-(3-pyrrolidin-1-ylpropyl)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(Br)=CC=C2C(=O)N1CCCN1CCCC1 DQUIAHUPHBKSJV-UHFFFAOYSA-N 0.000 description 2
- FMQVWUSDOGZNOP-GFCCVEGCSA-N 6-fluoro-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(F)C=C2CC1 FMQVWUSDOGZNOP-GFCCVEGCSA-N 0.000 description 2
- QAYARJVVFMRVQJ-UHFFFAOYSA-N 6-fluoro-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=CC(F)=CC=C21 QAYARJVVFMRVQJ-UHFFFAOYSA-N 0.000 description 2
- FFQPMFRXDKZTSI-UHFFFAOYSA-N 6-methoxy-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinoline Chemical compound C1CC2=CC(OC)=CC=C2CN1CCN1CCCC1 FFQPMFRXDKZTSI-UHFFFAOYSA-N 0.000 description 2
- YTUGKSPWSXYXIP-UHFFFAOYSA-N 6-piperidin-1-yl-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NCCC2=CC=1N1CCCCC1 YTUGKSPWSXYXIP-UHFFFAOYSA-N 0.000 description 2
- GBJPMDRESWPSCJ-UHFFFAOYSA-N 7-bromo-2-prop-2-enyl-3,4-dihydroisoquinolin-1-one Chemical compound C1CN(CC=C)C(=O)C2=CC(Br)=CC=C21 GBJPMDRESWPSCJ-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 101001016833 Homo sapiens Histamine H3 receptor Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- SNIABFMMCKVXSY-UHFFFAOYSA-N benzoylazanium;chloride Chemical class Cl.NC(=O)C1=CC=CC=C1 SNIABFMMCKVXSY-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- UCAIEVHKDLMIFL-UHFFFAOYSA-N clobenpropit Chemical compound C1=CC(Cl)=CC=C1CNC(=N)SCCCC1=CNC=N1 UCAIEVHKDLMIFL-UHFFFAOYSA-N 0.000 description 2
- 230000003931 cognitive performance Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000012059 conventional drug carrier Substances 0.000 description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- ACQBHJXEAYTHCY-UHFFFAOYSA-N cyclopropyl-[4-[3-(1H-imidazol-5-yl)propoxy]phenyl]methanone Chemical compound C=1C=C(OCCCC=2NC=NC=2)C=CC=1C(=O)C1CC1 ACQBHJXEAYTHCY-UHFFFAOYSA-N 0.000 description 2
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 description 2
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical compound C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- 231100000863 loss of memory Toxicity 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- UIEWEAUCYZJTST-QGZVFWFLSA-N methyl 4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-7-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(CCN(CCN2[C@@H](CCC2)C)C2=O)C2=C1 UIEWEAUCYZJTST-QGZVFWFLSA-N 0.000 description 2
- SGFACFBLUAWICV-UHFFFAOYSA-N methyl 4-bromo-2-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1CBr SGFACFBLUAWICV-UHFFFAOYSA-N 0.000 description 2
- MSEBQGULDWDIRW-UHFFFAOYSA-N methyl 4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1 MSEBQGULDWDIRW-UHFFFAOYSA-N 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 230000001722 neurochemical effect Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229910052762 osmium Inorganic materials 0.000 description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 230000037322 slow-wave sleep Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- PQCXFUXRTRESBD-UHFFFAOYSA-N (4-methoxycarbonylphenyl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)C=C1 PQCXFUXRTRESBD-UHFFFAOYSA-N 0.000 description 1
- VDUKDQTYMWUSAC-UHFFFAOYSA-N (4-methylsulfonylphenyl)boronic acid Chemical compound CS(=O)(=O)C1=CC=C(B(O)O)C=C1 VDUKDQTYMWUSAC-UHFFFAOYSA-N 0.000 description 1
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 description 1
- QIQWRCNAPQJQLL-COALEZEGSA-N (z)-but-2-enedioic acid;5-[(1r,2r)-2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1h-imidazole Chemical compound OC(=O)\C=C/C(O)=O.CC(C)(C)CCC#C[C@@H]1C[C@H]1C1=CN=CN1 QIQWRCNAPQJQLL-COALEZEGSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- DJMOXMNDXFFONV-UHFFFAOYSA-N 1,3-dimethyl-7-[2-(n-methylanilino)ethyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCN(C)C1=CC=CC=C1 DJMOXMNDXFFONV-UHFFFAOYSA-N 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- GZPMMQGPHXEMSZ-UHFFFAOYSA-N 1-(methoxymethyl)pyrrolidine Chemical compound COCN1CCCC1 GZPMMQGPHXEMSZ-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- WIGRVUWJNPVKPB-UHFFFAOYSA-N 1-methylpyrrolidin-1-ium;chloride Chemical compound Cl.CN1CCCC1 WIGRVUWJNPVKPB-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- YHYLDEVWYOFIJK-UHFFFAOYSA-N 1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC=CC2=C1 YHYLDEVWYOFIJK-UHFFFAOYSA-N 0.000 description 1
- MZVKNFPDQWHQKT-UHFFFAOYSA-N 2,4-difluoro-6-nitrophenol Chemical compound OC1=C(F)C=C(F)C=C1[N+]([O-])=O MZVKNFPDQWHQKT-UHFFFAOYSA-N 0.000 description 1
- GCUOLJOTJRUDIZ-UHFFFAOYSA-N 2-(2-bromoethoxy)oxane Chemical compound BrCCOC1CCCCO1 GCUOLJOTJRUDIZ-UHFFFAOYSA-N 0.000 description 1
- WMDHQEHPOVOEOG-UHFFFAOYSA-N 2-(2-bromoethyl)-1,3-dioxane Chemical compound BrCCC1OCCCO1 WMDHQEHPOVOEOG-UHFFFAOYSA-N 0.000 description 1
- QTEWPEYOZMFHBU-UHFFFAOYSA-N 2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-ol Chemical compound C1CC2=CC(O)=CC=C2CN1CCN1CCCC1 QTEWPEYOZMFHBU-UHFFFAOYSA-N 0.000 description 1
- IZMREWVFEJXIBO-UHFFFAOYSA-N 2-(3-phenylpropylsulfanylmethyl)-1,3,4-oxadiazole Chemical group C=1C=CC=CC=1CCCSCC1=NN=CO1 IZMREWVFEJXIBO-UHFFFAOYSA-N 0.000 description 1
- WPYPBKZVMIMAHI-UHFFFAOYSA-N 2-(6-bromo-3-oxo-1h-isoindol-2-yl)acetaldehyde Chemical compound BrC1=CC=C2C(=O)N(CC=O)CC2=C1 WPYPBKZVMIMAHI-UHFFFAOYSA-N 0.000 description 1
- ACDJGEXCTSRDGX-UHFFFAOYSA-N 2-(6-iodo-1-oxo-3,4-dihydroisoquinolin-2-yl)acetaldehyde Chemical compound O=C1N(CC=O)CCC2=CC(I)=CC=C21 ACDJGEXCTSRDGX-UHFFFAOYSA-N 0.000 description 1
- CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical group FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 description 1
- GYLXLBXNEQCIJN-UHFFFAOYSA-N 2-[2-(2-phenoxyethylamino)ethyl]-1h-1,2,4-triazol-3-one Chemical group O=C1NC=NN1CCNCCOC1=CC=CC=C1 GYLXLBXNEQCIJN-UHFFFAOYSA-N 0.000 description 1
- RZPHSSGYCPDTIC-UHFFFAOYSA-N 2-[2-(ethylamino)ethyl]-6-piperidin-1-yl-3,4-dihydroisoquinolin-1-one;hydrochloride Chemical class Cl.C=1C=C2C(=O)N(CCNCC)CCC2=CC=1N1CCCCC1 RZPHSSGYCPDTIC-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical compound NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 description 1
- BPGIOCZAQDIBPI-UHFFFAOYSA-N 2-ethoxyethanamine Chemical compound CCOCCN BPGIOCZAQDIBPI-UHFFFAOYSA-N 0.000 description 1
- BFYGWTXKXGLZBY-UHFFFAOYSA-N 2-methoxy-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC=C2C(=O)N(OC)CCC2=C1 BFYGWTXKXGLZBY-UHFFFAOYSA-N 0.000 description 1
- BUOUXUXFUAMANS-UHFFFAOYSA-N 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-1-one Chemical compound C=1C=C2C(=O)N(C)CCC2=CC=1B1OC(C)(C)C(C)(C)O1 BUOUXUXFUAMANS-UHFFFAOYSA-N 0.000 description 1
- JRYYVMDEUJQWRO-UHFFFAOYSA-N 2-methylnicotinamide Chemical compound CC1=NC=CC=C1C(N)=O JRYYVMDEUJQWRO-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- IMLAIXAZMVDRGA-UHFFFAOYSA-N 2-phenoxyethanamine Chemical compound NCCOC1=CC=CC=C1 IMLAIXAZMVDRGA-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
- CWYJEQUZYGSELV-UHFFFAOYSA-N 3-(6-bromo-1-oxo-3,4-dihydroisoquinolin-2-yl)propanal Chemical compound O=C1N(CCC=O)CCC2=CC(Br)=CC=C21 CWYJEQUZYGSELV-UHFFFAOYSA-N 0.000 description 1
- LWTQXFCQLGPDAI-UHFFFAOYSA-N 3-bromo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-1-one Chemical compound BrC1CC2=CC=CC=C2C(=O)N1CCN1CCCC1 LWTQXFCQLGPDAI-UHFFFAOYSA-N 0.000 description 1
- IERAZGHDRKYYIE-OAHLLOKOSA-N 3-fluoro-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzoic acid Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C(=CC(=CC=3)C(O)=O)F)C=C2CC1 IERAZGHDRKYYIE-OAHLLOKOSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- BWRWNUQAQPAYCK-UHFFFAOYSA-N 3-methoxypyrrolidine Chemical compound COC1CCNC1 BWRWNUQAQPAYCK-UHFFFAOYSA-N 0.000 description 1
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 1
- GWRSATNRNFYMDI-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound FC=1C=C(NC=2N=C3N(C4CCCC4)CC(F)(F)C(=O)N(C)C3=CN=2)C(OC)=CC=1C(=O)NC1CCN(C)CC1 GWRSATNRNFYMDI-UHFFFAOYSA-N 0.000 description 1
- FBLSKYXQDYGDOR-UHFFFAOYSA-N 4-[1-oxo-2-(3-piperidin-1-ylpropyl)-3,4-dihydroisoquinolin-6-yl]benzonitrile;hydrochloride Chemical compound Cl.C1CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2C(=O)N1CCCN1CCCCC1 FBLSKYXQDYGDOR-UHFFFAOYSA-N 0.000 description 1
- QZCWWDQVNXLPEW-UHFFFAOYSA-N 4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(CN(CCN2CCCC2)CC2)C2=C1 QZCWWDQVNXLPEW-UHFFFAOYSA-N 0.000 description 1
- MXRTWAZUXNCTKW-MRXNPFEDSA-N 4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzoic acid Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C(O)=O)C=C2CC1 MXRTWAZUXNCTKW-MRXNPFEDSA-N 0.000 description 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- KLLMUIDJDQXKHM-UHFFFAOYSA-N 4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]-n-propan-2-ylbenzamide Chemical compound C1=CC(C(=O)NC(C)C)=CC=C1OC1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 KLLMUIDJDQXKHM-UHFFFAOYSA-N 0.000 description 1
- RKYVLWZPAAHCFD-GMUIIQOCSA-N 4-[[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(OCC=3C=CC(=CC=3)C#N)C=C2CC1 RKYVLWZPAAHCFD-GMUIIQOCSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- UVVYFYLSZIMKMC-UHFFFAOYSA-N 4-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=CC2=C1CCC2=O UVVYFYLSZIMKMC-UHFFFAOYSA-N 0.000 description 1
- RVCJOGNLYVNRDN-UHFFFAOYSA-N 4-bromo-2-methylbenzoic acid Chemical compound CC1=CC(Br)=CC=C1C(O)=O RVCJOGNLYVNRDN-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- NQVQYJRVQBNGSU-UHFFFAOYSA-N 5-(benzimidazol-1-ylmethyl)-2-bromobenzaldehyde Chemical compound C1=C(C=O)C(Br)=CC=C1CN1C2=CC=CC=C2N=C1 NQVQYJRVQBNGSU-UHFFFAOYSA-N 0.000 description 1
- KSONICAHAPRCMV-UHFFFAOYSA-N 5-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2C(=O)CCC2=C1 KSONICAHAPRCMV-UHFFFAOYSA-N 0.000 description 1
- QDTQAMUJNAKRQD-LLVKDONJSA-N 5-bromo-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3h-isoindol-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(Br)C=C2C1 QDTQAMUJNAKRQD-LLVKDONJSA-N 0.000 description 1
- QOPRWBRNMPANKN-UHFFFAOYSA-N 5-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2C(=O)CCC2=C1 QOPRWBRNMPANKN-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- REFDYZWHMVDGRM-QGZVFWFLSA-N 6-(4-fluorophenyl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydro-1h-isoquinoline Chemical compound C[C@@H]1CCCN1CCN1CC2=CC=C(C=3C=CC(F)=CC=3)C=C2CC1 REFDYZWHMVDGRM-QGZVFWFLSA-N 0.000 description 1
- GPBFLYUZYFABML-GOSISDBHSA-N 6-(azepane-1-carbonyl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)N3CCCCCC3)C=C2CC1 GPBFLYUZYFABML-GOSISDBHSA-N 0.000 description 1
- NSSMXABOIJRQRP-QGZVFWFLSA-N 6-(benzimidazol-1-yl)-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(N3C4=CC=CC=C4N=C3)C=C2CC1 NSSMXABOIJRQRP-QGZVFWFLSA-N 0.000 description 1
- FOJBCPQRKSWSJH-UHFFFAOYSA-N 6-[(1-oxo-3,4-dihydro-2h-isoquinolin-6-yl)oxy]pyridine-3-carbonitrile Chemical compound C=1C=C2C(=O)NCCC2=CC=1OC1=CC=C(C#N)C=N1 FOJBCPQRKSWSJH-UHFFFAOYSA-N 0.000 description 1
- MBCXHGPCHRZRCW-UHFFFAOYSA-N 6-[[1-oxo-2-(2-oxoethyl)-3,4-dihydroisoquinolin-6-yl]oxy]pyridine-3-carbonitrile Chemical compound C=1C=C2C(=O)N(CC=O)CCC2=CC=1OC1=CC=C(C#N)C=N1 MBCXHGPCHRZRCW-UHFFFAOYSA-N 0.000 description 1
- SEQHEDQNODAFIU-UHFFFAOYSA-N 6-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2CCC(=O)C2=C1 SEQHEDQNODAFIU-UHFFFAOYSA-N 0.000 description 1
- BETBLRBFDUFZDB-UHFFFAOYSA-N 6-bromo-2-[2-(1,3-dioxan-2-yl)ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(Br)=CC=C2C(=O)N1CCC1OCCCO1 BETBLRBFDUFZDB-UHFFFAOYSA-N 0.000 description 1
- DEYOMDZKXMQLCF-UHFFFAOYSA-N 6-chloro-n-methylpyridine-3-carboxamide Chemical compound CNC(=O)C1=CC=C(Cl)N=C1 DEYOMDZKXMQLCF-UHFFFAOYSA-N 0.000 description 1
- ORIQLMBUPMABDV-UHFFFAOYSA-N 6-chloropyridine-3-carbonitrile Chemical compound ClC1=CC=C(C#N)C=N1 ORIQLMBUPMABDV-UHFFFAOYSA-N 0.000 description 1
- SWZXUFXMIOFFLI-GFCCVEGCSA-N 6-iodo-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(I)C=C2CC1 SWZXUFXMIOFFLI-GFCCVEGCSA-N 0.000 description 1
- NZRSQRSFFPSTKO-UHFFFAOYSA-N 6-iodo-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=CC(I)=CC=C21 NZRSQRSFFPSTKO-UHFFFAOYSA-N 0.000 description 1
- WLQWIZAWNPYMBR-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=CC(OC)=CC=C21 WLQWIZAWNPYMBR-UHFFFAOYSA-N 0.000 description 1
- PPAMJICPFOOUEZ-GFCCVEGCSA-N 7-bromo-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydroisoquinolin-1-one Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC(Br)=CC=C2CC1 PPAMJICPFOOUEZ-GFCCVEGCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010013142 Disinhibition Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 102100032508 Histamine H3 receptor Human genes 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FHQDWPCFSJMNCT-UHFFFAOYSA-N N(tele)-methylhistamine Chemical compound CN1C=NC(CCN)=C1 FHQDWPCFSJMNCT-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000862969 Stella Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- RFMWZKFFCVOYPE-UHFFFAOYSA-N [2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl] trifluoromethanesulfonate Chemical compound C1CC2=CC(OS(=O)(=O)C(F)(F)F)=CC=C2CN1CCN1CCCC1 RFMWZKFFCVOYPE-UHFFFAOYSA-N 0.000 description 1
- DZISASHRVPJVCE-CYBMUJFWSA-N [2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-3,4-dihydro-1h-isoquinolin-6-yl] trifluoromethanesulfonate Chemical compound C[C@@H]1CCCN1CCN1CC2=CC=C(OS(=O)(=O)C(F)(F)F)C=C2CC1 DZISASHRVPJVCE-CYBMUJFWSA-N 0.000 description 1
- KFHYZKCRXNRKRC-MRXNPFEDSA-N abt-239 Chemical compound C[C@@H]1CCCN1CCC1=CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2O1 KFHYZKCRXNRKRC-MRXNPFEDSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003935 attention Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- PQZTVWVYCLIIJY-UHFFFAOYSA-N diethyl(propyl)amine Chemical group CCCN(CC)CC PQZTVWVYCLIIJY-UHFFFAOYSA-N 0.000 description 1
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 1
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical group CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000013100 final test Methods 0.000 description 1
- ZHOGHWVKKXUAPI-UHFFFAOYSA-N fluorooxy(phenyl)borinic acid Chemical compound FOB(O)C1=CC=CC=C1 ZHOGHWVKKXUAPI-UHFFFAOYSA-N 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- DDRPCXLAQZKBJP-UHFFFAOYSA-N furfurylamine Chemical compound NCC1=CC=CO1 DDRPCXLAQZKBJP-UHFFFAOYSA-N 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000003453 histamine agonist Substances 0.000 description 1
- 230000000742 histaminergic effect Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000002296 hyperlocomotor Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000001153 interneuron Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000005056 memory consolidation Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000003924 mental process Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960001252 methamphetamine Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- FJLHHAXLFMDJBZ-UHFFFAOYSA-N methyl 3-fluoro-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzoate Chemical compound FC1=CC(C(=O)OC)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 FJLHHAXLFMDJBZ-UHFFFAOYSA-N 0.000 description 1
- MGNGIMOZJXKZIF-MRXNPFEDSA-N methyl 3-fluoro-4-[2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzoate Chemical compound FC1=CC(C(=O)OC)=CC=C1C1=CC=C(C(=O)N(CCN2[C@@H](CCC2)C)CC2)C2=C1 MGNGIMOZJXKZIF-MRXNPFEDSA-N 0.000 description 1
- IBVPKEQXLFPHKX-UHFFFAOYSA-N methyl 4-[2-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1h-isoquinolin-6-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(CN(CCN2CCCC2)CC2)C2=C1 IBVPKEQXLFPHKX-UHFFFAOYSA-N 0.000 description 1
- XJAPZIHVTLNGMH-UHFFFAOYSA-N methyl 4-[[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]oxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 XJAPZIHVTLNGMH-UHFFFAOYSA-N 0.000 description 1
- SNUSCKYSFXHLBO-UHFFFAOYSA-N methyl 5-(benzimidazol-1-ylmethyl)-2-bromobenzoate Chemical compound C1=C(Br)C(C(=O)OC)=CC(CN2C3=CC=CC=C3N=C2)=C1 SNUSCKYSFXHLBO-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- VEGKMRUZYWQMBZ-UHFFFAOYSA-N n,n-dimethyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C1=CC=C(C(=O)N(CCN2CCCC2)CC2)C2=C1 VEGKMRUZYWQMBZ-UHFFFAOYSA-N 0.000 description 1
- ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- GZHMKYZLKCTRJG-OAHLLOKOSA-N n-cyclobutyl-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinoline-6-carboxamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)NC3CCC3)C=C2CC1 GZHMKYZLKCTRJG-OAHLLOKOSA-N 0.000 description 1
- QEQQBHZIYAODLH-UHFFFAOYSA-N n-cyclobutyl-4-[1-oxo-2-(2-pyrrolidin-1-ylethyl)-3,4-dihydroisoquinolin-6-yl]benzamide Chemical compound C=1C=C(C=2C=C3CCN(CCN4CCCC4)C(=O)C3=CC=2)C=CC=1C(=O)NC1CCC1 QEQQBHZIYAODLH-UHFFFAOYSA-N 0.000 description 1
- MDXDGYHSKINVMQ-QGZVFWFLSA-N n-cyclohexyl-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinoline-6-carboxamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)NC3CCCCC3)C=C2CC1 MDXDGYHSKINVMQ-QGZVFWFLSA-N 0.000 description 1
- XKDHGBLTUPENCN-MRXNPFEDSA-N n-cyclopentyl-2-[2-[(2r)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinoline-6-carboxamide Chemical compound C[C@@H]1CCCN1CCN1C(=O)C2=CC=C(C(=O)NC3CCCC3)C=C2CC1 XKDHGBLTUPENCN-MRXNPFEDSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- OTYPIDNRISCWQY-UHFFFAOYSA-L palladium(2+);tris(2-methylphenyl)phosphane;dichloride Chemical compound Cl[Pd]Cl.CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C.CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C OTYPIDNRISCWQY-UHFFFAOYSA-L 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003414 procognitive effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- OBLVPWTUALCMGD-UHFFFAOYSA-N pyridin-1-ium-3-carboxamide;chloride Chemical compound Cl.NC(=O)C1=CC=CN=C1 OBLVPWTUALCMGD-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 230000004622 sleep time Effects 0.000 description 1
- 230000008454 sleep-wake cycle Effects 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 230000004036 social memory Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011697 sodium iodate Substances 0.000 description 1
- 235000015281 sodium iodate Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 230000006886 spatial memory Effects 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- FKKJJPMGAWGYPN-UHFFFAOYSA-N thiophen-2-ylmethanamine Chemical compound NCC1=CC=CS1 FKKJJPMGAWGYPN-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- UNEPXPMBVGDXGH-UHFFFAOYSA-N tributyl(pyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=NC=C1 UNEPXPMBVGDXGH-UHFFFAOYSA-N 0.000 description 1
- 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000002792 vascular Effects 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
Classifications
-
- 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
- C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/02—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 containing two hetero rings
- C07D401/12—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 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/14—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 containing three or more hetero rings
-
- 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
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US99363607P | 2007-09-12 | 2007-09-12 | |
| US60/993,636 | 2007-09-12 | ||
| PCT/US2008/075981 WO2009036144A1 (en) | 2007-09-12 | 2008-09-11 | Isoquinolinyl and isoindolinyl derivatives as histamine-3 antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2699384A1 true CA2699384A1 (en) | 2009-03-19 |
Family
ID=40261509
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2699384A Abandoned CA2699384A1 (en) | 2007-09-12 | 2008-09-11 | Isoquinolinyl and isoindolinyl derivatives as histamine-3 antagonists |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US20090069300A1 (enExample) |
| EP (1) | EP2200989A1 (enExample) |
| JP (1) | JP2010539180A (enExample) |
| KR (1) | KR20100054856A (enExample) |
| CN (1) | CN101848896A (enExample) |
| AP (1) | AP2010005202A0 (enExample) |
| AR (1) | AR068423A1 (enExample) |
| AU (1) | AU2008298926A1 (enExample) |
| BR (1) | BRPI0817061A2 (enExample) |
| CA (1) | CA2699384A1 (enExample) |
| CL (1) | CL2008002726A1 (enExample) |
| CO (1) | CO6300955A2 (enExample) |
| CR (1) | CR11303A (enExample) |
| DO (1) | DOP2010000079A (enExample) |
| EA (1) | EA201000316A1 (enExample) |
| EC (1) | ECSP10010025A (enExample) |
| MA (1) | MA31699B1 (enExample) |
| MX (1) | MX2010002760A (enExample) |
| NI (1) | NI201000036A (enExample) |
| PA (1) | PA8795701A1 (enExample) |
| PE (1) | PE20090651A1 (enExample) |
| TN (1) | TN2010000105A1 (enExample) |
| TW (1) | TW200927114A (enExample) |
| WO (1) | WO2009036144A1 (enExample) |
| ZA (1) | ZA201001751B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200823204A (en) * | 2006-10-17 | 2008-06-01 | Arena Pharm Inc | Biphenyl sulfonyl and phenyl-heteroaryl sulfonyl modulators of the histamine H3-receptor useful for the treatment of disorders related thereto |
| GB0907284D0 (en) | 2009-04-28 | 2009-06-10 | Queen Mary & Westfield College | Compounds for inducing cellular apoptosis |
| CN102725290B (zh) * | 2009-07-27 | 2016-03-09 | 吉利德科学股份有限公司 | 作为离子通道调节剂的稠合杂环化合物 |
| ES2529119T3 (es) | 2010-07-02 | 2015-02-17 | Gilead Sciences, Inc. | Compuestos heterocíclicos condensados como moduladores de canales iónicos |
| WO2012058133A1 (en) * | 2010-10-29 | 2012-05-03 | Merck Sharp & Dohme Corp. | Isoindolinone pde10 inhibitors |
| TWI510480B (zh) * | 2011-05-10 | 2015-12-01 | Gilead Sciences Inc | 充當離子通道調節劑之稠合雜環化合物 |
| NO3175985T3 (enExample) | 2011-07-01 | 2018-04-28 | ||
| TWI549944B (zh) | 2011-07-01 | 2016-09-21 | 吉李德科學股份有限公司 | 作為離子通道調節劑之稠合雜環化合物 |
| EP2729007A1 (de) | 2011-07-04 | 2014-05-14 | Bayer Intellectual Property GmbH | Verwendung substituierter isochinolinone, isochinolindione, isochinolintrione und dihydroisochinolinone oder jeweils deren salze als wirkstoffe gegen abiotischen pflanzenstress |
| WO2013076590A1 (en) | 2011-11-23 | 2013-05-30 | Oxygen Healthcare Research Pvt. Ltd | Benzothiazine compounds as h3 receptor ligands |
| CN105254554B (zh) * | 2014-07-14 | 2018-01-30 | 南开大学 | 一种制备异吲哚啉酮类化合物的方法 |
| EP4132646A1 (en) * | 2020-04-08 | 2023-02-15 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| CN116368130A (zh) | 2020-08-28 | 2023-06-30 | 金橘生物科技公司 | 杂环化合物及其用途 |
| CN115819347B (zh) * | 2022-11-14 | 2024-08-30 | 暨明医药科技（苏州）有限公司 | 一种1-烷基-3-溴吡唑的制备方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3933829A (en) * | 1974-08-22 | 1976-01-20 | John Wyeth & Brother Limited | 4-Aminoquinoline derivatives |
| US4159331A (en) * | 1978-05-05 | 1979-06-26 | The Upjohn Company | Antihypertensive 4-aminoquinolines |
| US4166853A (en) * | 1978-05-05 | 1979-09-04 | The Upjohn Company | Antihypertensive 7-trifluoromethyl-4-aminoquinolones |
| IL117149A0 (en) * | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| AU7270798A (en) * | 1997-05-01 | 1998-11-24 | Eli Lilly And Company | Antithrombotic agents |
| AU2002254114A1 (en) | 2001-03-23 | 2002-10-08 | Eli Lilly And Company | Non-imidazole aryl alkylamines compounds as histamine h3 receptor antagonists, preparation and therapeutic uses |
| PL212616B1 (pl) * | 2002-09-19 | 2012-10-31 | Lilly Co Eli | Eter diarylowy i kompozycja farmaceutyczna zawierajaca ten eter |
| HRP20080120T5 (hr) * | 2004-05-14 | 2012-07-31 | Millennium@Pharmaceuticals | Spojevi i postupci za inhibiciju napredovanja mitoze s pomoću inhibicije aurora kinaze |
| US20060014733A1 (en) * | 2004-07-19 | 2006-01-19 | Pfizer Inc | Histamine-3 agonists and antagonists |
| US7381732B2 (en) * | 2004-10-26 | 2008-06-03 | Bristol-Myers Squibb Company | Pyrazolobenzamides and derivatives as factor Xa inhibitors |
| CA2595157A1 (en) * | 2005-01-21 | 2006-07-27 | Schering Corporation | Imidazole and benzimidazole derivatives useful as histamine h3 antagonists |
| US20070032475A1 (en) * | 2005-04-15 | 2007-02-08 | Ye Xiaocong M | Novel compounds useful for bradykinin B1 receptor antagonism |
-
2008
- 2008-09-11 MX MX2010002760A patent/MX2010002760A/es not_active Application Discontinuation
- 2008-09-11 AU AU2008298926A patent/AU2008298926A1/en not_active Abandoned
- 2008-09-11 AP AP2010005202A patent/AP2010005202A0/xx unknown
- 2008-09-11 EA EA201000316A patent/EA201000316A1/ru unknown
- 2008-09-11 CN CN200880106892A patent/CN101848896A/zh active Pending
- 2008-09-11 EP EP08799453A patent/EP2200989A1/en not_active Withdrawn
- 2008-09-11 JP JP2010524978A patent/JP2010539180A/ja not_active Withdrawn
- 2008-09-11 CA CA2699384A patent/CA2699384A1/en not_active Abandoned
- 2008-09-11 KR KR1020107007943A patent/KR20100054856A/ko not_active Ceased
- 2008-09-11 WO PCT/US2008/075981 patent/WO2009036144A1/en not_active Ceased
- 2008-09-11 BR BRPI0817061 patent/BRPI0817061A2/pt not_active Application Discontinuation
- 2008-09-11 US US12/208,794 patent/US20090069300A1/en not_active Abandoned
- 2008-09-12 AR ARP080103964A patent/AR068423A1/es not_active Application Discontinuation
- 2008-09-12 PE PE2008001597A patent/PE20090651A1/es not_active Application Discontinuation
- 2008-09-12 TW TW097135281A patent/TW200927114A/zh unknown
- 2008-09-12 CL CL200802726A patent/CL2008002726A1/es unknown
- 2008-09-12 PA PA20088795701A patent/PA8795701A1/es unknown
-
2010
- 2010-03-04 CR CR11303A patent/CR11303A/es not_active Application Discontinuation
- 2010-03-05 TN TNP2010000105A patent/TN2010000105A1/fr unknown
- 2010-03-10 EC EC2010010025A patent/ECSP10010025A/es unknown
- 2010-03-11 NI NI201000036A patent/NI201000036A/es unknown
- 2010-03-11 DO DO2010000079A patent/DOP2010000079A/es unknown
- 2010-03-11 ZA ZA2010/01751A patent/ZA201001751B/en unknown
- 2010-03-12 MA MA32688A patent/MA31699B1/fr unknown
- 2010-03-15 CO CO10030398A patent/CO6300955A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CR11303A (es) | 2010-03-18 |
| BRPI0817061A2 (pt) | 2015-03-24 |
| ZA201001751B (en) | 2010-11-24 |
| NI201000036A (es) | 2010-08-13 |
| PE20090651A1 (es) | 2009-05-28 |
| AP2010005202A0 (en) | 2010-04-30 |
| EP2200989A1 (en) | 2010-06-30 |
| MA31699B1 (fr) | 2010-09-01 |
| WO2009036144A1 (en) | 2009-03-19 |
| TN2010000105A1 (fr) | 2011-09-26 |
| CN101848896A (zh) | 2010-09-29 |
| ECSP10010025A (es) | 2010-08-31 |
| AU2008298926A1 (en) | 2009-03-19 |
| CO6300955A2 (es) | 2011-07-21 |
| TW200927114A (en) | 2009-07-01 |
| CL2008002726A1 (es) | 2008-10-10 |
| EA201000316A1 (ru) | 2010-10-29 |
| MX2010002760A (es) | 2010-04-01 |
| DOP2010000079A (es) | 2010-03-31 |
| US20090069300A1 (en) | 2009-03-12 |
| JP2010539180A (ja) | 2010-12-16 |
| AR068423A1 (es) | 2009-11-18 |
| PA8795701A1 (es) | 2009-04-23 |
| KR20100054856A (ko) | 2010-05-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2699384A1 (en) | Isoquinolinyl and isoindolinyl derivatives as histamine-3 antagonists | |
| KR102228764B1 (ko) | 키나제 억제제로서의 헤테로시클릭 아미드 | |
| CN111170999B (zh) | Egfr抑制剂及其制备和应用 | |
| AU2008298983A1 (en) | Azacyclylisoquinolinone and isoindolinone derivatives as histamine-3 antagonists | |
| CN107406426B (zh) | 作为rock抑制剂的环状脲类 | |
| EP2488520B1 (en) | Condensed azine-derivatives for the treatment of diseases related to the acetylcholine receptor | |
| WO2008131779A1 (en) | Isoquinolinone derivatives as nk3 antagonists | |
| AU2017203454A1 (en) | Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof | |
| EP3849968B1 (en) | 1h-indazole carboxamides as receptor-interacting protein kinase 1 inhibitors (ripk1) | |
| EP3548468A1 (en) | Tricyclic rho kinase inhibitors | |
| WO2015077193A1 (en) | Inhibitors of lysine methyl transferase | |
| CN106632243B (zh) | 吡咯烷衍生物 | |
| CA2693138A1 (en) | Aminoalkylazole derivatives as histamine-3 antagonists | |
| EP2150534A1 (en) | Isoquinolinone derivatives as nk3 antagonists | |
| HK1144815A (en) | Isoquinolinyl and isoindolinyl derivatives as histamine-3 antagonists | |
| CA2602532A1 (en) | Pyrrolo [2,3-d] imidazoles for the treatment of hyperproliferative disorders | |
| HK1143583A (en) | Azacyclylisoquinolinone and isoindolinone derivatives as histamine-3 antagonists | |
| HK1213545B (en) | Heterocyclic amides as kinase inhibitors | |
| MX2007006555A (en) | N-substituted benzimidazolyl c-kit inhibitors and combinatorial benzimidazole library |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130904 |