CA2827724A1 - Substituted 6,7-dialkoxy-3-isoquinolinol derivatives as inhibitors of phosphodiesterase 10 (pde10a) - Google Patents

Info

Publication number

CA2827724A1

CA2827724A1 CA2827724A CA2827724A CA2827724A1 CA 2827724 A1 CA2827724 A1 CA 2827724A1 CA 2827724 A CA2827724 A CA 2827724A CA 2827724 A CA2827724 A CA 2827724A CA 2827724 A1 CA2827724 A1 CA 2827724A1

Authority

CA

Canada

Prior art keywords

methyl

dimethoxy

disorder

dihydrochloride

arh

Prior art date

2011-02-18

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

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• Global Dossier
• CIPO
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• 239000003112 inhibitor Substances 0.000 title abstract description 13
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title abstract description 10
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title abstract description 10
• 150000001875 compounds Chemical class 0.000 claims abstract description 121
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• 238000000034 method Methods 0.000 claims description 181
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 154
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 143
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• -1 azido, hydroxy Chemical group 0.000 claims description 55
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• GYPOFOQUZZUVQL-UHFFFAOYSA-N 2h-isoquinolin-3-one Chemical compound C1=CC=C2C=NC(O)=CC2=C1 GYPOFOQUZZUVQL-UHFFFAOYSA-N 0.000 claims description 21
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• 125000003545 alkoxy group Chemical group 0.000 claims description 13
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• 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
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• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 5
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• BGTMPYLBFUAQHC-UHFFFAOYSA-N 1-ethyl-6,7-dimethoxy-4-(naphthalen-2-ylmethyl)-2h-isoquinolin-3-one;hydrochloride Chemical compound Cl.C12=CC(OC)=C(OC)C=C2C(CC)=NC(O)=C1CC1=CC=C(C=CC=C2)C2=C1 BGTMPYLBFUAQHC-UHFFFAOYSA-N 0.000 claims description 4
• HFVNDVLCVJBYIK-UHFFFAOYSA-N 3,6,7-trimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinoline;hydrochloride Chemical compound Cl.C1=CC=CC2=CC(CC=3C(OC)=NC(C)=C4C=C(C(=CC4=3)OC)OC)=CC=C21 HFVNDVLCVJBYIK-UHFFFAOYSA-N 0.000 claims description 4
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• FMSANJIVZDRHEG-UHFFFAOYSA-N 4-(isoquinolin-5-ylmethyl)-6,7-dimethoxy-1-methyl-2h-isoquinolin-3-one Chemical compound N1=CC=C2C(CC=3C(O)=NC(C)=C4C=C(C(=CC4=3)OC)OC)=CC=CC2=C1 FMSANJIVZDRHEG-UHFFFAOYSA-N 0.000 claims description 4
• DVDXVRDJQQVUQP-UHFFFAOYSA-N 4-(isoquinolin-6-ylmethyl)-6,7-dimethoxy-1-methyl-2h-isoquinolin-3-one;dihydrochloride Chemical compound Cl.Cl.C1=NC=CC2=CC(CC=3C(O)=NC(C)=C4C=C(C(=CC4=3)OC)OC)=CC=C21 DVDXVRDJQQVUQP-UHFFFAOYSA-N 0.000 claims description 4
• PKHZFDNFJKIBGX-UHFFFAOYSA-N 6,7-dimethoxy-1-methyl-4-(quinolin-6-ylmethyl)-2h-isoquinolin-3-one;dihydrochloride Chemical compound Cl.Cl.N1=CC=CC2=CC(CC=3C(O)=NC(C)=C4C=C(C(=CC4=3)OC)OC)=CC=C21 PKHZFDNFJKIBGX-UHFFFAOYSA-N 0.000 claims description 4
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• ZOOFOWYODXELAA-UHFFFAOYSA-N 6,7-dimethoxy-4-[[6-methoxy-2-(2,2,2-trifluoroethylamino)quinolin-3-yl]methyl]-1-propan-2-yl-2h-isoquinolin-3-one;dihydrochloride Chemical compound Cl.Cl.COC1=C(OC)C=C2C(CC=3C(NCC(F)(F)F)=NC4=CC=C(C=C4C=3)OC)=C(O)N=C(C(C)C)C2=C1 ZOOFOWYODXELAA-UHFFFAOYSA-N 0.000 claims description 3
• MHURYTZHRWHSAM-UHFFFAOYSA-N 6,7-dimethoxy-4-[[6-methoxy-2-(methylamino)quinolin-3-yl]methyl]-1-propyl-2h-isoquinolin-3-one;dihydrochloride Chemical compound Cl.Cl.C12=CC(OC)=C(OC)C=C2C(CCC)=NC(O)=C1CC1=CC2=CC(OC)=CC=C2N=C1NC MHURYTZHRWHSAM-UHFFFAOYSA-N 0.000 claims description 3
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
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• ZWRMGTDJFIHXIG-UHFFFAOYSA-N 4-[[2-(ethylamino)-7-fluoro-6-methoxyquinolin-3-yl]methyl]-6,7-dimethoxy-1-propyl-2h-isoquinolin-3-one;dihydrochloride Chemical compound Cl.Cl.C12=CC(OC)=C(OC)C=C2C(CCC)=NC(O)=C1CC1=CC2=CC(OC)=C(F)C=C2N=C1NCC ZWRMGTDJFIHXIG-UHFFFAOYSA-N 0.000 claims 1
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• YZDNDYZIYOBDLJ-UHFFFAOYSA-N 4-[[6-ethoxy-2-(ethylamino)-7-fluoroquinolin-3-yl]methyl]-6,7-dimethoxy-1-propyl-2h-isoquinolin-3-one;dihydrochloride Chemical compound Cl.Cl.C12=CC(OC)=C(OC)C=C2C(CCC)=NC(O)=C1CC1=CC2=CC(OCC)=C(F)C=C2N=C1NCC YZDNDYZIYOBDLJ-UHFFFAOYSA-N 0.000 claims 1
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• KBYPBHQYLMZWOF-UHFFFAOYSA-N 6,7-dimethoxy-1-propyl-4-(quinolin-3-ylmethyl)-2h-isoquinolin-3-one;dihydrochloride Chemical compound Cl.Cl.C12=CC(OC)=C(OC)C=C2C(CCC)=NC(O)=C1CC1=CN=C(C=CC=C2)C2=C1 KBYPBHQYLMZWOF-UHFFFAOYSA-N 0.000 claims 1
• JJHGVTORLVSJBS-UHFFFAOYSA-N 6,7-dimethoxy-4-[[6-methoxy-2-(propan-2-ylamino)quinolin-3-yl]methyl]-1-propyl-2h-isoquinolin-3-one;dihydrochloride Chemical compound Cl.Cl.C12=CC(OC)=C(OC)C=C2C(CCC)=NC(O)=C1CC1=CC2=CC(OC)=CC=C2N=C1NC(C)C JJHGVTORLVSJBS-UHFFFAOYSA-N 0.000 claims 1
• GNAZSOBKJRSETJ-UHFFFAOYSA-N [1-(acetamidomethyl)-4-[[2-(ethylamino)-6-methoxyquinolin-3-yl]methyl]-6,7-dimethoxyisoquinolin-3-yl] acetate Chemical compound COC1=C(OC)C=C2C(CC3=CC4=CC(OC)=CC=C4N=C3NCC)=C(OC(C)=O)N=C(CNC(C)=O)C2=C1 GNAZSOBKJRSETJ-UHFFFAOYSA-N 0.000 claims 1
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