NZ553160A - Anilino-substituted triazolophthalazine derivatives having PDE2 inhibitory activity - Google Patents

Info

Publication number

NZ553160A

NZ553160A NZ553160A NZ55316005A NZ553160A NZ 553160 A NZ553160 A NZ 553160A NZ 553160 A NZ553160 A NZ 553160A NZ 55316005 A NZ55316005 A NZ 55316005A NZ 553160 A NZ553160 A NZ 553160A

Authority

NZ

New Zealand

Prior art keywords

phenyl

methoxy

alkyl

alkoxy

morpholino

Prior art date

2004-09-02

Links

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• Global Dossier
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• -1 Anilino-substituted triazolophthalazine Chemical class 0.000 title claims abstract description 110
• 230000002401 inhibitory effect Effects 0.000 title claims description 10
• 101100135859 Dictyostelium discoideum regA gene Proteins 0.000 title claims 2
• 101100082606 Plasmodium falciparum (isolate 3D7) PDEbeta gene Proteins 0.000 title claims 2
• 101100135860 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PDE2 gene Proteins 0.000 title claims 2
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
• SGTXILTYXULEQD-UHFFFAOYSA-N 2H-triazolo[4,5-f]phthalazine Chemical class N1=NC=C2C3=NNN=C3C=CC2=C1 SGTXILTYXULEQD-UHFFFAOYSA-N 0.000 claims abstract description 12
• 230000000694 effects Effects 0.000 claims abstract description 10
• 206010029113 Neovascularisation Diseases 0.000 claims abstract description 8
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 6
• 206010003246 arthritis Diseases 0.000 claims abstract description 4
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 3
• 150000001875 compounds Chemical class 0.000 claims description 218
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 107
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 49
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
• 125000004573 morpholin-4-yl group Chemical class N1(CCOCC1)* 0.000 claims description 42
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 150000003839 salts Chemical class 0.000 claims description 36
• 125000004076 pyridyl group Chemical group 0.000 claims description 34
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 150000002367 halogens Chemical class 0.000 claims description 19
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
• 238000011282 treatment Methods 0.000 claims description 16
• 230000005764 inhibitory process Effects 0.000 claims description 14
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
• 239000000460 chlorine Chemical group 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 12
• 125000002541 furyl group Chemical group 0.000 claims description 12
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 12
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 11
• 125000003277 amino group Chemical group 0.000 claims description 10
• 208000035475 disorder Diseases 0.000 claims description 10
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
• 229910052794 bromium Inorganic materials 0.000 claims description 9
• 229910052731 fluorine Inorganic materials 0.000 claims description 9
• 239000011737 fluorine Chemical group 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
• 230000035699 permeability Effects 0.000 claims description 9
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
• 125000001544 thienyl group Chemical group 0.000 claims description 8
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 7
• 229920002554 vinyl polymer Chemical group 0.000 claims description 7
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• 230000001771 impaired effect Effects 0.000 claims description 5
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
• 206010040070 Septic Shock Diseases 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 238000003556 assay Methods 0.000 claims description 4
• 230000008497 endothelial barrier function Effects 0.000 claims description 4
• 230000003511 endothelial effect Effects 0.000 claims description 4
• 125000000951 phenoxy group Chemical class [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
• 230000036303 septic shock Effects 0.000 claims description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
• 230000001154 acute effect Effects 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 230000001684 chronic effect Effects 0.000 claims description 3
• 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
• 206010014561 Emphysema Diseases 0.000 claims description 2
• 206010030113 Oedema Diseases 0.000 claims description 2
• 206010035664 Pneumonia Diseases 0.000 claims description 2
• UNHAFLHFQYAMGK-UHFFFAOYSA-N [3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(C=CC=1)C(=O)N1CCN(C)CC1)C1=CC=CC=C12 UNHAFLHFQYAMGK-UHFFFAOYSA-N 0.000 claims description 2
• VMHDXDYHQQWOGS-UHFFFAOYSA-N [3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]-morpholin-4-ylmethanone Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(C=CC=1)C(=O)N1CCOCC1)C1=CC=CC=C12 VMHDXDYHQQWOGS-UHFFFAOYSA-N 0.000 claims description 2
• MEEYPFPMRFFNAY-UHFFFAOYSA-N [4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(=CC=1)C(=O)N1CCN(C)CC1)C1=CC=CC=C12 MEEYPFPMRFFNAY-UHFFFAOYSA-N 0.000 claims description 2
• WWGQSINQMBXELR-UHFFFAOYSA-N [4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]-morpholin-4-ylmethanone Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(=CC=1)C(=O)N1CCOCC1)C1=CC=CC=C12 WWGQSINQMBXELR-UHFFFAOYSA-N 0.000 claims description 2
• 206010006451 bronchitis Diseases 0.000 claims description 2
• 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
• ZOZGQHDQFRUORE-UHFFFAOYSA-N n-[4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(NC(=O)C3CC3)=CC=1)C1=CC=CC=C12 ZOZGQHDQFRUORE-UHFFFAOYSA-N 0.000 claims description 2
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
• 206010039083 rhinitis Diseases 0.000 claims description 2
• 230000002792 vascular Effects 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 18
• 201000011510 cancer Diseases 0.000 claims 1
• DURLJUGBZLEILS-UHFFFAOYSA-N n-[3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(NC(=O)C3CC3)C=CC=1)C1=CC=CC=C12 DURLJUGBZLEILS-UHFFFAOYSA-N 0.000 claims 1
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• 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 abstract description 2
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• 208000024891 symptom Diseases 0.000 abstract description 2
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
• 238000006243 chemical reaction Methods 0.000 description 30
• 238000000034 method Methods 0.000 description 30
• 229910052740 iodine Inorganic materials 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 19
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
• ZHGVCXDOKBSJBV-UHFFFAOYSA-N 6-chloro-3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(Cl)C1=CC=CC=C12 ZHGVCXDOKBSJBV-UHFFFAOYSA-N 0.000 description 17
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
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• 150000001448 anilines Chemical class 0.000 description 9
• 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 9
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• UQTJGZYAFKMABR-UHFFFAOYSA-N (4-chlorophthalazin-1-yl)hydrazine Chemical compound C1=CC=C2C(NN)=NN=C(Cl)C2=C1 UQTJGZYAFKMABR-UHFFFAOYSA-N 0.000 description 7
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