JP2008526715A - 神経精神障害の治療のためのアリールピペラジン誘導体 - Google Patents
神経精神障害の治療のためのアリールピペラジン誘導体 Download PDFInfo
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- JP2008526715A JP2008526715A JP2007548841A JP2007548841A JP2008526715A JP 2008526715 A JP2008526715 A JP 2008526715A JP 2007548841 A JP2007548841 A JP 2007548841A JP 2007548841 A JP2007548841 A JP 2007548841A JP 2008526715 A JP2008526715 A JP 2008526715A
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- Prior art keywords
- alkyl
- butyl
- piperazin
- cycloalkyl
- alkoxy
- Prior art date
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- -1 Aryl piperazine derivatives Chemical class 0.000 title claims description 72
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title claims description 6
- 239000000203 mixture Substances 0.000 claims abstract description 69
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 45
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 38
- 102000005962 receptors Human genes 0.000 claims abstract description 36
- 108020003175 receptors Proteins 0.000 claims abstract description 36
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 102000015554 Dopamine receptor Human genes 0.000 claims abstract description 18
- 108050004812 Dopamine receptor Proteins 0.000 claims abstract description 18
- 229960003638 dopamine Drugs 0.000 claims abstract description 17
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 claims abstract description 12
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 claims abstract description 12
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 119
- 125000003545 alkoxy group Chemical group 0.000 claims description 96
- 125000005843 halogen group Chemical group 0.000 claims description 90
- 238000000034 method Methods 0.000 claims description 84
- 125000001188 haloalkyl group Chemical group 0.000 claims description 82
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 74
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 73
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 71
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 71
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 71
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 70
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 69
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 65
- 239000001257 hydrogen Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 150000002431 hydrogen Chemical class 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 30
- 125000003342 alkenyl group Chemical group 0.000 claims description 29
- 208000035475 disorder Diseases 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000001041 indolyl group Chemical group 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 12
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 10
- 125000005605 benzo group Chemical group 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 239000005977 Ethylene Substances 0.000 claims description 8
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 8
- 125000004551 isoquinolin-3-yl group Chemical group C1=NC(=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000003367 polycyclic group Chemical group 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 208000022497 Cocaine-Related disease Diseases 0.000 claims description 6
- 206010013654 Drug abuse Diseases 0.000 claims description 6
- 208000028017 Psychotic disease Diseases 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- MBKIFLFRYIEMRC-UHFFFAOYSA-N n-[4-[4-(3-methoxyphenyl)piperazin-1-yl]butyl]-1-benzofuran-2-carboxamide Chemical compound COC1=CC=CC(N2CCN(CCCCNC(=O)C=3OC4=CC=CC=C4C=3)CC2)=C1 MBKIFLFRYIEMRC-UHFFFAOYSA-N 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- AEQHEVDDTLOOMD-UHFFFAOYSA-N 4-[4-[6-(4-phenylpiperazin-1-yl)hexyl]piperazin-1-yl]quinoline Chemical compound C1CN(C=2C3=CC=CC=C3N=CC=2)CCN1CCCCCCN(CC1)CCN1C1=CC=CC=C1 AEQHEVDDTLOOMD-UHFFFAOYSA-N 0.000 claims description 5
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- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 5
- 230000000926 neurological effect Effects 0.000 claims description 5
- 208000020016 psychiatric disease Diseases 0.000 claims description 5
- 208000011117 substance-related disease Diseases 0.000 claims description 5
- WONRMJRDFOBXPZ-UHFFFAOYSA-N 1-(3-methoxyphenyl)-4-[6-[4-(3-methylphenyl)piperazin-1-yl]hexyl]piperazine Chemical compound COC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3C=C(C)C=CC=3)CC2)=C1 WONRMJRDFOBXPZ-UHFFFAOYSA-N 0.000 claims description 4
- AWPASOZUABXVOH-UHFFFAOYSA-N 1-(3-methylphenyl)-4-[6-(4-phenylpiperazin-1-yl)hexyl]piperazine Chemical compound CC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3C=CC=CC=3)CC2)=C1 AWPASOZUABXVOH-UHFFFAOYSA-N 0.000 claims description 4
- GXAJAEYMTGMWDK-UHFFFAOYSA-N 1-(3-methylphenyl)-4-[6-(4-pyridin-2-ylpiperazin-1-yl)hexyl]piperazine Chemical compound CC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3N=CC=CC=3)CC2)=C1 GXAJAEYMTGMWDK-UHFFFAOYSA-N 0.000 claims description 4
- GPANICKLGIVBML-UHFFFAOYSA-N 2-[4-(6-methoxy-3,4-dihydro-1h-pyrazino[1,2-a]indol-2-yl)butyl]-3,4-dihydropyrazino[1,2-a]indol-1-one Chemical compound O=C1C2=CC3=CC=CC=C3N2CCN1CCCCN1CC2=CC(C=CC=C3OC)=C3N2CC1 GPANICKLGIVBML-UHFFFAOYSA-N 0.000 claims description 4
- WVTGLVGVGXUUSO-UHFFFAOYSA-N 2-[4-[4-(3-chlorophenyl)piperazin-1-yl]butyl]-3,4-dihydropyrazino[1,2-a]indol-1-one Chemical compound ClC1=CC=CC(N2CCN(CCCCN3C(C=4N(C5=CC=CC=C5C=4)CC3)=O)CC2)=C1 WVTGLVGVGXUUSO-UHFFFAOYSA-N 0.000 claims description 4
- BGYDPUKQSFICRF-UHFFFAOYSA-N 3-[5-[4-(3-chlorophenyl)piperazin-1-yl]pentoxy]isoquinoline Chemical compound ClC1=CC=CC(N2CCN(CCCCCOC=3N=CC4=CC=CC=C4C=3)CC2)=C1 BGYDPUKQSFICRF-UHFFFAOYSA-N 0.000 claims description 4
- GHIDUOFGICUEQZ-UHFFFAOYSA-N 3-[5-[4-(3-methylphenyl)piperazin-1-yl]pentoxy]isoquinoline Chemical compound CC1=CC=CC(N2CCN(CCCCCOC=3N=CC4=CC=CC=C4C=3)CC2)=C1 GHIDUOFGICUEQZ-UHFFFAOYSA-N 0.000 claims description 4
- ICWRMSXGSZIKFX-UHFFFAOYSA-N 4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl 1h-indole-2-carboxylate Chemical compound ClC1=CC=CC(N2CCN(CCCCOC(=O)C=3NC4=CC=CC=C4C=3)CC2)=C1Cl ICWRMSXGSZIKFX-UHFFFAOYSA-N 0.000 claims description 4
- YVYMJYSSXPEYLE-UHFFFAOYSA-N 4-[4-[6-[4-(3-methylphenyl)piperazin-1-yl]hexyl]piperazin-1-yl]quinoline Chemical compound CC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3C4=CC=CC=C4N=CC=3)CC2)=C1 YVYMJYSSXPEYLE-UHFFFAOYSA-N 0.000 claims description 4
- GEVGXHIEDPEZGZ-UHFFFAOYSA-N 7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-5h-pyrrolo[1,2-a]quinoxalin-4-one Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4C(N5C=CC=C5C(=O)N4)=CC=3)CC2)=C1Cl GEVGXHIEDPEZGZ-UHFFFAOYSA-N 0.000 claims description 4
- 241000282412 Homo Species 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 4
- 125000004254 isoquinolin-1-yl group Chemical group [H]C1=C([H])C2=C([H])C([H])=C([H])C([H])=C2C(*)=N1 0.000 claims description 4
- 125000004552 isoquinolin-4-yl group Chemical group C1=NC=C(C2=CC=CC=C12)* 0.000 claims description 4
- RXSPPURWVKBINN-UHFFFAOYSA-N n-[2-(1h-indol-3-yl)ethyl]-3-[4-(3-methoxyphenyl)piperazin-1-yl]propanamide Chemical compound COC1=CC=CC(N2CCN(CCC(=O)NCCC=3C4=CC=CC=C4NC=3)CC2)=C1 RXSPPURWVKBINN-UHFFFAOYSA-N 0.000 claims description 4
- QYQRBWOTZUGEKR-UHFFFAOYSA-N n-[2-(1h-indol-3-yl)ethyl]-3-[4-(3-methylphenyl)piperazin-1-yl]propanamide Chemical compound CC1=CC=CC(N2CCN(CCC(=O)NCCC=3C4=CC=CC=C4NC=3)CC2)=C1 QYQRBWOTZUGEKR-UHFFFAOYSA-N 0.000 claims description 4
- BMLRTLPESFVXBM-UHFFFAOYSA-N n-[4-(4-pyridin-2-ylpiperazin-1-yl)butyl]isoquinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2C=NC=1C(=O)NCCCCN(CC1)CCN1C1=CC=CC=N1 BMLRTLPESFVXBM-UHFFFAOYSA-N 0.000 claims description 4
- XIGIDLFCLUMLLT-UHFFFAOYSA-N n-[4-(5-methoxy-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl)butyl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NCCCCN3CC=4NC=5C=CC=C(C=5C=4CC3)OC)=CC2=C1 XIGIDLFCLUMLLT-UHFFFAOYSA-N 0.000 claims description 4
- UTOISRMSYNWABJ-UHFFFAOYSA-N n-[4-(6-methoxy-3,4-dihydro-1h-pyrazino[1,2-a]indol-2-yl)butyl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NCCCCN3CC4=CC=5C=CC=C(C=5N4CC3)OC)=CC2=C1 UTOISRMSYNWABJ-UHFFFAOYSA-N 0.000 claims description 4
- UPKZNVQHJZHSGN-UHFFFAOYSA-N n-[4-[4-(3-chlorophenyl)piperazin-1-yl]butyl]isoquinoline-3-carboxamide Chemical compound ClC1=CC=CC(N2CCN(CCCCNC(=O)C=3N=CC4=CC=CC=C4C=3)CC2)=C1 UPKZNVQHJZHSGN-UHFFFAOYSA-N 0.000 claims description 4
- AFUIBDRITZEBAF-UHFFFAOYSA-N n-[4-[4-(3-cyanophenyl)piperazin-1-yl]butyl]-1-benzofuran-2-carboxamide Chemical compound C=1C2=CC=CC=C2OC=1C(=O)NCCCCN(CC1)CCN1C1=CC=CC(C#N)=C1 AFUIBDRITZEBAF-UHFFFAOYSA-N 0.000 claims description 4
- VJMYWLHHQXMODZ-UHFFFAOYSA-N n-[4-[4-(3-methoxyphenyl)piperazin-1-yl]butyl]isoquinoline-3-carboxamide Chemical compound COC1=CC=CC(N2CCN(CCCCNC(=O)C=3N=CC4=CC=CC=C4C=3)CC2)=C1 VJMYWLHHQXMODZ-UHFFFAOYSA-N 0.000 claims description 4
- HIHVVYZXHODHBR-UHFFFAOYSA-N n-[4-[4-(3-methoxyphenyl)piperazin-1-yl]butyl]pyridine-2-carboxamide Chemical compound COC1=CC=CC(N2CCN(CCCCNC(=O)C=3N=CC=CC=3)CC2)=C1 HIHVVYZXHODHBR-UHFFFAOYSA-N 0.000 claims description 4
- DIJKUIXRAWOVGJ-UHFFFAOYSA-N n-[4-[4-(3-methylphenyl)piperazin-1-yl]butyl]-1-benzofuran-2-carboxamide Chemical compound CC1=CC=CC(N2CCN(CCCCNC(=O)C=3OC4=CC=CC=C4C=3)CC2)=C1 DIJKUIXRAWOVGJ-UHFFFAOYSA-N 0.000 claims description 4
- UVSLSTOAZHUYRU-UHFFFAOYSA-N n-[4-[4-(3-methylphenyl)piperazin-1-yl]butyl]isoquinoline-3-carboxamide Chemical compound CC1=CC=CC(N2CCN(CCCCNC(=O)C=3N=CC4=CC=CC=C4C=3)CC2)=C1 UVSLSTOAZHUYRU-UHFFFAOYSA-N 0.000 claims description 4
- DMVANBWXLUGNDG-UHFFFAOYSA-N n-[4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]butyl]-1h-indole-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CCCCNC(=O)C=3NC4=CC=CC=C4C=3)CC2)=C1 DMVANBWXLUGNDG-UHFFFAOYSA-N 0.000 claims description 4
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims description 4
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
- YWGRWBCJUGEEBA-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-[6-[4-(3-chlorophenyl)piperazin-1-yl]hexyl]piperazine Chemical compound ClC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3C=C(Cl)C=CC=3)CC2)=C1 YWGRWBCJUGEEBA-UHFFFAOYSA-N 0.000 claims description 3
- LHRSLSNYJPWXLS-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-[6-[4-(3-methoxyphenyl)piperazin-1-yl]hexyl]piperazine Chemical compound COC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3C=C(Cl)C=CC=3)CC2)=C1 LHRSLSNYJPWXLS-UHFFFAOYSA-N 0.000 claims description 3
- IMWNCWRNMUKPGO-UHFFFAOYSA-N 1-(3-methoxyphenyl)-4-[6-[4-(3-methoxyphenyl)piperazin-1-yl]hexyl]piperazine Chemical compound COC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3C=C(OC)C=CC=3)CC2)=C1 IMWNCWRNMUKPGO-UHFFFAOYSA-N 0.000 claims description 3
- CQEUVRXXXLSTIL-UHFFFAOYSA-N 1-(3-methylphenyl)-4-[6-[4-(3-methylphenyl)piperazin-1-yl]hexyl]piperazine Chemical compound CC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3C=C(C)C=CC=3)CC2)=C1 CQEUVRXXXLSTIL-UHFFFAOYSA-N 0.000 claims description 3
- PBQPCCMEDMVKBH-UHFFFAOYSA-N 1-(3-methylphenyl)-4-[6-[4-(6-methylpyridin-2-yl)piperazin-1-yl]hexyl]piperazine Chemical compound CC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3N=C(C)C=CC=3)CC2)=C1 PBQPCCMEDMVKBH-UHFFFAOYSA-N 0.000 claims description 3
- RZIJMFBERNFJML-UHFFFAOYSA-N 1-(6-methylpyridin-2-yl)-4-[6-(4-phenylpiperazin-1-yl)hexyl]piperazine Chemical compound CC1=CC=CC(N2CCN(CCCCCCN3CCN(CC3)C=3C=CC=CC=3)CC2)=N1 RZIJMFBERNFJML-UHFFFAOYSA-N 0.000 claims description 3
- ORESESSHUCUUFK-UHFFFAOYSA-N 1-phenyl-4-[6-(4-phenylpiperazin-1-yl)hexyl]piperazine Chemical compound C1CN(C=2C=CC=CC=2)CCN1CCCCCCN(CC1)CCN1C1=CC=CC=C1 ORESESSHUCUUFK-UHFFFAOYSA-N 0.000 claims description 3
- BWMDINMAJBXMLE-UHFFFAOYSA-N 1-phenyl-4-[6-(4-pyridin-2-ylpiperazin-1-yl)hexyl]piperazine Chemical compound C1CN(C=2C=CC=CC=2)CCN1CCCCCCN(CC1)CCN1C1=CC=CC=N1 BWMDINMAJBXMLE-UHFFFAOYSA-N 0.000 claims description 3
- OSEVIYJKDQCRJK-UHFFFAOYSA-N 1-pyridin-2-yl-4-[6-(4-pyridin-2-ylpiperazin-1-yl)hexyl]piperazine Chemical compound C1CN(C=2N=CC=CC=2)CCN1CCCCCCN(CC1)CCN1C1=CC=CC=N1 OSEVIYJKDQCRJK-UHFFFAOYSA-N 0.000 claims description 3
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- FJYOWAGOWYSGRX-UHFFFAOYSA-N n-[4-[4-(3-methoxyphenyl)piperazin-1-yl]butyl]-1h-indole-3-carboxamide Chemical compound COC1=CC=CC(N2CCN(CCCCNC(=O)C=3C4=CC=CC=C4NC=3)CC2)=C1 FJYOWAGOWYSGRX-UHFFFAOYSA-N 0.000 claims description 3
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- 238000006467 substitution reaction Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- UERPGEIDWQLDIE-UHFFFAOYSA-N tert-butyl 4-(6-methoxypyridin-2-yl)piperazine-1-carboxylate Chemical compound COC1=CC=CC(N2CCN(CC2)C(=O)OC(C)(C)C)=N1 UERPGEIDWQLDIE-UHFFFAOYSA-N 0.000 description 1
- QEDVZUFNZJJSJL-UHFFFAOYSA-N tert-butyl 4-(6-methylpyridin-2-yl)piperazine-1-carboxylate Chemical compound CC1=CC=CC(N2CCN(CC2)C(=O)OC(C)(C)C)=N1 QEDVZUFNZJJSJL-UHFFFAOYSA-N 0.000 description 1
- SMGXVMGZQKGYAY-UHFFFAOYSA-N tert-butyl 4-quinolin-4-ylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=NC2=CC=CC=C12 SMGXVMGZQKGYAY-UHFFFAOYSA-N 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
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 125000004951 trihalomethoxy group Chemical group 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
Classifications
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/108—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Organic Chemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Quinoline Compounds (AREA)
- Furan Compounds (AREA)
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| DKPA200500004 | 2005-01-03 | ||
| US64100605P | 2005-01-04 | 2005-01-04 | |
| PCT/EP2006/050001 WO2006072608A2 (en) | 2005-01-03 | 2006-01-02 | Aryl piperazine derivatives for the treatment of neuropsychiatric disorders |
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| JP2008526715A true JP2008526715A (ja) | 2008-07-24 |
| JP2008526715A5 JP2008526715A5 (enExample) | 2009-02-19 |
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| US (1) | US20090238761A1 (enExample) |
| EP (1) | EP1836192A2 (enExample) |
| JP (1) | JP2008526715A (enExample) |
| AU (1) | AU2006204522A1 (enExample) |
| CA (1) | CA2593266A1 (enExample) |
| NZ (1) | NZ555491A (enExample) |
| WO (1) | WO2006072608A2 (enExample) |
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| JP2015536921A (ja) * | 2012-10-11 | 2015-12-24 | サザン リサーチ インスティテュート | アミノアルキルピペラジンの尿素及びアミド誘導体並びにその使用 |
| JP2016516829A (ja) * | 2013-04-23 | 2016-06-09 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | ピラジノ[1,2−a]インドール化合物、その調製および医薬としての使用 |
| JP2017537938A (ja) * | 2014-12-17 | 2017-12-21 | アジェンデ・キミケ・リウニテ・アンジェリニ・フランチェスコ・ア・チ・エレ・ア・エフェ・ソシエタ・ペル・アチオニAziende Chimiche Riunite Angelini Francesco A.C.R.A.F.Societa Per Azioni | 新しい抗菌性化合物 |
| JP2018150349A (ja) * | 2012-05-09 | 2018-09-27 | サノビオン ファーマシューティカルズ インクSunovion Pharmaceuticals Inc. | ヘテロアリール化合物及びその使用方法 |
| JPWO2018168738A1 (ja) * | 2017-03-13 | 2019-11-21 | 大日本住友製薬株式会社 | 2,6−ジ置換ピリジン誘導体 |
| JP2020509088A (ja) * | 2017-02-24 | 2020-03-26 | 深▲チェン▼市霊蘭生物医薬科技有限公司Shenzhen Linglan Bio−Pharmaceutical Technology Co., Ltd | 新規なドーパミンd3受容体選択的リガンド及びびその調製方法並びに医薬使用 |
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| FR2903986A1 (fr) * | 2006-07-21 | 2008-01-25 | Pierre Fabre Medicament Sa | Nouveaux derives chromenes ou thiochromenes carboxamides, leur procede de preparation et leurs applications en therapeutique |
| GB0615809D0 (en) * | 2006-08-09 | 2006-09-20 | Istituto Di Ricerche D Biolog | Therapeutic compounds |
| CA2672920A1 (en) * | 2006-10-13 | 2008-04-17 | Universita'degli Studi Di Siena | Aryl piperazine derivatives useful for the treatment of neuropsychiatric disorders |
| EP2114948B1 (en) * | 2006-12-28 | 2014-06-25 | AbbVie Inc. | Inhibitors of poly(adp-ribose)polymerase |
| AU2007354861B2 (en) * | 2007-06-15 | 2013-03-21 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use |
| US20110002855A1 (en) * | 2007-06-25 | 2011-01-06 | Neurogen Corporation | Piperazinyl oxoalkyl tetrahydro-beta-carbolines and related analogues |
| EP2238125A1 (en) * | 2008-02-01 | 2010-10-13 | NeuroSearch A/S | Novel aryl piperazine derivatives useful as modulators of dopamine and serotonin receptors |
| WO2010040808A1 (en) * | 2008-10-10 | 2010-04-15 | Neurosearch A/S | Novel quinolinylamide derivatives useful as modulators of dopamine and serotonin receptors |
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| WO2015014256A1 (en) | 2013-07-29 | 2015-02-05 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use thereof |
| EP3083589B1 (en) | 2013-12-20 | 2019-12-18 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use thereof |
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| WO2001049677A1 (en) * | 1999-12-30 | 2001-07-12 | H. Lundbeck A/S | Phenylpiperazinyl derivatives |
| JP2002532481A (ja) * | 1998-12-17 | 2002-10-02 | アメリカン・ホーム・プロダクツ・コーポレイション | 5−ht1a受容体活性を有するピペラジンエチルアミド誘導体 |
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| US4954502A (en) * | 1988-06-10 | 1990-09-04 | Bristol-Myers Squibb Company | 1-indolyalkyl-4-(substituted-pyridinyl)piperazines |
| GB9306578D0 (en) * | 1993-03-30 | 1993-05-26 | Merck Sharp & Dohme | Therapeutic agents |
| CA2498936C (en) | 2002-09-14 | 2013-02-12 | Gov't Of The Usa As Represented By The Secretary Of The Department Of Health & Human Services | Structurally rigid dopamine d3 receptor selective ligands and process for making them |
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- 2006-01-02 CA CA002593266A patent/CA2593266A1/en not_active Abandoned
- 2006-01-02 WO PCT/EP2006/050001 patent/WO2006072608A2/en not_active Ceased
- 2006-01-02 EP EP06700234A patent/EP1836192A2/en not_active Withdrawn
- 2006-01-02 NZ NZ555491A patent/NZ555491A/en not_active IP Right Cessation
- 2006-01-02 AU AU2006204522A patent/AU2006204522A1/en not_active Abandoned
- 2006-01-02 JP JP2007548841A patent/JP2008526715A/ja active Pending
- 2006-01-02 US US11/794,687 patent/US20090238761A1/en not_active Abandoned
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| WO2004112729A2 (en) * | 2003-06-19 | 2004-12-29 | Psychiatric Genomics, Inc. | Dual function compounds and uses thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018150349A (ja) * | 2012-05-09 | 2018-09-27 | サノビオン ファーマシューティカルズ インクSunovion Pharmaceuticals Inc. | ヘテロアリール化合物及びその使用方法 |
| JP2015536921A (ja) * | 2012-10-11 | 2015-12-24 | サザン リサーチ インスティテュート | アミノアルキルピペラジンの尿素及びアミド誘導体並びにその使用 |
| JP2016516829A (ja) * | 2013-04-23 | 2016-06-09 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | ピラジノ[1,2−a]インドール化合物、その調製および医薬としての使用 |
| JP2017537938A (ja) * | 2014-12-17 | 2017-12-21 | アジェンデ・キミケ・リウニテ・アンジェリニ・フランチェスコ・ア・チ・エレ・ア・エフェ・ソシエタ・ペル・アチオニAziende Chimiche Riunite Angelini Francesco A.C.R.A.F.Societa Per Azioni | 新しい抗菌性化合物 |
| JP2020509088A (ja) * | 2017-02-24 | 2020-03-26 | 深▲チェン▼市霊蘭生物医薬科技有限公司Shenzhen Linglan Bio−Pharmaceutical Technology Co., Ltd | 新規なドーパミンd3受容体選択的リガンド及びびその調製方法並びに医薬使用 |
| JP7017797B2 (ja) | 2017-02-24 | 2022-02-09 | 深▲チェン▼市霊蘭生物医薬科技有限公司 | 新規なドーパミンd3受容体選択的リガンド及びびその調製方法並びに医薬使用 |
| JPWO2018168738A1 (ja) * | 2017-03-13 | 2019-11-21 | 大日本住友製薬株式会社 | 2,6−ジ置換ピリジン誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2593266A1 (en) | 2006-07-13 |
| AU2006204522A1 (en) | 2006-07-13 |
| US20090238761A1 (en) | 2009-09-24 |
| WO2006072608A3 (en) | 2006-09-28 |
| WO2006072608A2 (en) | 2006-07-13 |
| NZ555491A (en) | 2010-01-29 |
| EP1836192A2 (en) | 2007-09-26 |
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