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
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- 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
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- 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
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- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Other In-Based Heterocyclic Compounds (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)
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| CA2699384A1 true CA2699384A1 (en) | 2009-03-19 |
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| CA2699384A Abandoned CA2699384A1 (en) | 2007-09-12 | 2008-09-11 | Isoquinolinyl and isoindolinyl derivatives as histamine-3 antagonists |
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| 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 |
| PT2464645T (pt) * | 2009-07-27 | 2017-10-11 | Gilead Sciences Inc | Compostos heterocíclicos fusionados como moduladores do canal de iões |
| WO2012003392A1 (en) | 2010-07-02 | 2012-01-05 | Gilead Sciences, Inc. | Fused heterocyclic compounds as ion channel modulators |
| EP2632461A4 (en) * | 2010-10-29 | 2014-04-02 | Merck Sharp & Dohme | Isoindolinone PDE10 INHIBITORS |
| AU2012253653A1 (en) * | 2011-05-10 | 2013-05-02 | Gilead Sciences, Inc. | Fused heterocyclic compounds as sodium channel modulators |
| NO3175985T3 (enExample) | 2011-07-01 | 2018-04-28 | ||
| TWI622583B (zh) | 2011-07-01 | 2018-05-01 | 基利科學股份有限公司 | 作為離子通道調節劑之稠合雜環化合物 |
| US9173395B2 (en) | 2011-07-04 | 2015-11-03 | Bayer Intellectual Property Gmbh | Use of substituted isoquinolinones, isoquinolindiones, isoquinolintriones and dihydroisoquinolinones or in each case salts thereof as active agents against abiotic stress in plants |
| 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 |
| US20230167093A1 (en) * | 2020-04-08 | 2023-06-01 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| EP4203952A4 (en) | 2020-08-28 | 2024-12-11 | Kumquat Biosciences Inc. | HETEROCYCLIC COMPOUNDS AND USES THEREOF |
| US12496297B1 (en) * | 2020-10-23 | 2025-12-16 | Washington University | Compositions of autophagy modulating agents and uses thereof |
| 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)
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| US3933829A (en) * | 1974-08-22 | 1976-01-20 | John Wyeth & Brother Limited | 4-Aminoquinoline derivatives |
| US4166853A (en) * | 1978-05-05 | 1979-09-04 | The Upjohn Company | Antihypertensive 7-trifluoromethyl-4-aminoquinolones |
| US4159331A (en) * | 1978-05-05 | 1979-06-26 | The Upjohn Company | Antihypertensive 4-aminoquinolines |
| IL117149A0 (en) * | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| CA2287984A1 (en) * | 1997-05-01 | 1998-11-05 | Gerald Floyd Smith | Antithrombotic agents |
| WO2002076925A2 (en) | 2001-03-23 | 2002-10-03 | Eli Lilly And Company | Non-imidazole aryl alkylamines compounds as histamine h3 receptor antagonists, preparation and therapeutic uses |
| MY140236A (en) * | 2002-09-19 | 2009-12-31 | Lilly Co Eli | Diarylether compounds useful as opioid receptor antagonists |
| ATE381566T1 (de) * | 2004-05-14 | 2008-01-15 | Millennium Pharm Inc | Verbindungen und verfahren zur inhibierung der mitotischen progression durch hemmung von aurorakinase |
| 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 |
| EP1848696A1 (en) * | 2005-01-21 | 2007-10-31 | Schering Corporation | Imidazole and benzimidazole derivates useful as histamine h3 antagonists |
| JP2008537953A (ja) * | 2005-04-15 | 2008-10-02 | エラン ファーマシューティカルズ，インコーポレイテッド | ブラジキニンｂ１受容体拮抗作用に有用な新規化合物 |
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| WO2009036144A1 (en) | 2009-03-19 |
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| NI201000036A (es) | 2010-08-13 |
| ECSP10010025A (es) | 2010-08-31 |
| MX2010002760A (es) | 2010-04-01 |
| EA201000316A1 (ru) | 2010-10-29 |
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| CR11303A (es) | 2010-03-18 |
| TN2010000105A1 (fr) | 2011-09-26 |
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| PE20090651A1 (es) | 2009-05-28 |
| AU2008298926A1 (en) | 2009-03-19 |
| US20090069300A1 (en) | 2009-03-12 |
| TW200927114A (en) | 2009-07-01 |
| CO6300955A2 (es) | 2011-07-21 |
| CN101848896A (zh) | 2010-09-29 |
| MA31699B1 (fr) | 2010-09-01 |
| KR20100054856A (ko) | 2010-05-25 |
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| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130904 |