EA014324B1 - Триазолофталазины - Google Patents
Триазолофталазины Download PDFInfo
- Publication number
- EA014324B1 EA014324B1 EA200700537A EA200700537A EA014324B1 EA 014324 B1 EA014324 B1 EA 014324B1 EA 200700537 A EA200700537 A EA 200700537A EA 200700537 A EA200700537 A EA 200700537A EA 014324 B1 EA014324 B1 EA 014324B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- phenyl
- denotes
- group
- compounds
- triazolo
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 220
- -1 amino, carboxyl Chemical group 0.000 claims description 113
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 98
- 238000000034 method Methods 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 37
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 125000004076 pyridyl group Chemical group 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 23
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 22
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000003277 amino group Chemical group 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000002541 furyl group Chemical class 0.000 claims description 10
- 125000002140 imidazol-4-yl group Chemical class [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 10
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 10
- 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 10
- SGTXILTYXULEQD-UHFFFAOYSA-N 2H-triazolo[4,5-f]phthalazine Chemical group N1=NC=C2C3=NNN=C3C=CC2=C1 SGTXILTYXULEQD-UHFFFAOYSA-N 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 206010029113 Neovascularisation Diseases 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 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
- 230000000694 effects Effects 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
- QSDOKFGRSJQNMX-UHFFFAOYSA-N 4-(2-aminoethoxy)phenol Chemical compound NCCOC1=CC=C(O)C=C1 QSDOKFGRSJQNMX-UHFFFAOYSA-N 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 230000001575 pathological effect Effects 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
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 6
- 206010040070 Septic Shock Diseases 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 230000001771 impaired effect Effects 0.000 claims description 6
- 230000036303 septic shock Effects 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 5
- 208000017667 Chronic Disease Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 230000008497 endothelial barrier function Effects 0.000 claims description 5
- 230000003511 endothelial effect Effects 0.000 claims description 5
- 210000002345 respiratory system Anatomy 0.000 claims description 5
- 239000000126 substance Substances 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
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 4
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 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
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 206010014561 Emphysema Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 206010030113 Oedema Diseases 0.000 claims description 3
- 206010035664 Pneumonia Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 230000003211 malignant effect Effects 0.000 claims description 3
- 125000000951 phenoxy group Chemical class [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 206010039083 rhinitis Diseases 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 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
- 125000004195 4-methylpiperazin-1-yl group Chemical class [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 3
- BMVNFJCUHHTZQU-UHFFFAOYSA-N 4,5,6,7-tetrabromo-1,3-dihydrobenzimidazol-2-one Chemical compound BrC1=C(Br)C(Br)=C2NC(O)=NC2=C1Br BMVNFJCUHHTZQU-UHFFFAOYSA-N 0.000 claims 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims 2
- NULJZZQMTQVLPG-UHFFFAOYSA-N n,n-dimethylmorpholin-4-amine Chemical class CN(C)N1CCOCC1 NULJZZQMTQVLPG-UHFFFAOYSA-N 0.000 claims 2
- 101001098814 Dictyostelium discoideum 3',5'-cyclic-nucleotide phosphodiesterase regA Proteins 0.000 claims 1
- 101100135859 Dictyostelium discoideum regA gene Proteins 0.000 claims 1
- 101100082606 Plasmodium falciparum (isolate 3D7) PDEbeta gene Proteins 0.000 claims 1
- 101100135860 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PDE2 gene Proteins 0.000 claims 1
- 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 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 229940121828 Phosphodiesterase 2 inhibitor Drugs 0.000 abstract description 9
- 238000006243 chemical reaction Methods 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- 229910052740 iodine Inorganic materials 0.000 description 22
- 239000007858 starting material Substances 0.000 description 22
- 230000005764 inhibitory process Effects 0.000 description 20
- 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 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 230000035699 permeability Effects 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 150000001448 anilines Chemical class 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 7
- 108090000190 Thrombin Proteins 0.000 description 7
- 239000000443 aerosol Substances 0.000 description 7
- 229940126208 compound 22 Drugs 0.000 description 7
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Natural products CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 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 7
- 229960004072 thrombin Drugs 0.000 description 7
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 6
- NOGLKLPOGQJKKT-UHFFFAOYSA-N 3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]benzoic acid Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(C=CC=1)C(O)=O)C1=CC=CC=C12 NOGLKLPOGQJKKT-UHFFFAOYSA-N 0.000 description 6
- XXXJSWZTEOFKLH-UHFFFAOYSA-N 4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]benzoic acid Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(=CC=1)C(O)=O)C1=CC=CC=C12 XXXJSWZTEOFKLH-UHFFFAOYSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- MVATUPBWNNHYBN-UHFFFAOYSA-N n-[4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(NC(C)=O)=CC=1)C1=CC=CC=C12 MVATUPBWNNHYBN-UHFFFAOYSA-N 0.000 description 6
- 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 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- NENVQQVAZMKJJY-UHFFFAOYSA-N 3-n-[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]benzene-1,3-diamine Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(N)C=CC=1)C1=CC=CC=C12 NENVQQVAZMKJJY-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 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 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- SALUVRRAXFYBBV-UHFFFAOYSA-N n-[4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]benzamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(NC(=O)C=3C=CC=CC=3)=CC=1)C1=CC=CC=C12 SALUVRRAXFYBBV-UHFFFAOYSA-N 0.000 description 5
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- 150000003254 radicals Chemical class 0.000 description 5
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- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 4
- NPFVRBCDMFKOPY-UHFFFAOYSA-N 3-(4-imidazol-1-ylthiophen-2-yl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC(N2C=NC=C2)=CS1 NPFVRBCDMFKOPY-UHFFFAOYSA-N 0.000 description 4
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- WOFARLZTIGJRJV-UHFFFAOYSA-N n-[3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(NC(C)=O)C=CC=1)C1=CC=CC=C12 WOFARLZTIGJRJV-UHFFFAOYSA-N 0.000 description 4
- VHKBYKJUMAOGLE-UHFFFAOYSA-N n-[3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]benzamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(NC(=O)C=3C=CC=CC=3)C=CC=1)C1=CC=CC=C12 VHKBYKJUMAOGLE-UHFFFAOYSA-N 0.000 description 4
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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 3
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- 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
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Landscapes
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Applications Claiming Priority (2)
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| EP04104221 | 2004-09-02 | ||
| PCT/EP2005/054266 WO2006024640A2 (en) | 2004-09-02 | 2005-08-31 | Triazolophthalazines |
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| EA200700537A1 EA200700537A1 (ru) | 2007-10-26 |
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| EA012505B1 (ru) * | 2005-01-05 | 2009-10-30 | Никомед Гмбх | Триазолофталазины в качестве ингибиторов pde-2 |
| JP5130053B2 (ja) * | 2005-01-05 | 2013-01-30 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | トリアゾロフタラジン |
| PH12012501361A1 (en) | 2009-12-31 | 2012-10-22 | Centro Nac De Investigaciones Oncologicas Cnio | Tricyclic compounds for use as kinase inhibitors |
| US9540379B2 (en) | 2011-01-31 | 2017-01-10 | Boehringer Ingelheim International Gmbh | (1,2,4)triazolo[4,3-A]quinoxaline derivatives as inhibitors of phosphodiesterases |
| US20140045856A1 (en) | 2012-07-31 | 2014-02-13 | Boehringer Ingelheim International Gmbh | 4-Methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
| EP3087060B1 (en) | 2013-12-23 | 2020-05-13 | Merck Sharp & Dohme Corp. | Pyrimidone carboxamide compounds as pde2 inhibitors |
| EP3091983B1 (en) | 2014-01-08 | 2019-10-02 | Intra-Cellular Therapies, Inc. | Pharmaceutical compositions comprising a pde-1 inhibitor and a pde-2 inhibitor |
| HRP20212035T1 (hr) | 2014-04-23 | 2022-04-01 | Dart Neuroscience Llc | Pripravci koji sadrže supstituirane [1,2,4]triazolo[1,5-a]pirimidin-7-il spojeve kao inhibitore pde2 |
| TWI568737B (zh) | 2014-11-05 | 2017-02-01 | 達特神經科學（開曼）有限責任公司 | 作為ｐｄｅ２抑制劑之經取代的５－甲基－［１，２，４］三唑并［１，５－ａ］嘧啶－２－胺化合物 |
| AU2015357498B2 (en) | 2014-12-06 | 2019-09-12 | Intra-Cellular Therapies, Inc. | Organic compounds |
| MX371158B (es) | 2014-12-06 | 2020-01-20 | Intra Cellular Therapies Inc | Compuestos inhibidores de pde2. |
| WO2016145614A1 (en) | 2015-03-17 | 2016-09-22 | Merck Sharp & Dohme Corp. | Triazolyl pyrimidinone compounds as pde2 inhibitors |
| US10287269B2 (en) | 2015-03-26 | 2019-05-14 | Merck Sharp & Dohme Corp. | Pyrazolyl pyrimidinone compounds as PDE2 inhibitors |
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| WO2017000277A1 (en) | 2015-07-01 | 2017-01-05 | Merck Sharp & Dohme Corp. | Substituted triazolo bicycliccompounds as pde2 inhibitors |
| WO2017000276A1 (en) | 2015-07-01 | 2017-01-05 | Merck Sharp & Dohme Corp. | Bicyclic heterocyclic compounds as pde2 inhibitors |
| EP3156405A1 (en) | 2015-10-13 | 2017-04-19 | Boehringer Ingelheim International GmbH | Spirocyclic ether derivatives of pyrazolo[1,5-a]pyrimidine-3-carboxamide |
| JP2021504466A (ja) | 2017-11-23 | 2021-02-15 | オスロ ウニヴェルシティ ホスピタル ホーエフ | 頻脈の治療 |
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| EP0728759A1 (en) * | 1995-02-24 | 1996-08-28 | Ono Pharmaceutical Co., Ltd. | Heterocyclic compounds |
| RU2128175C1 (ru) * | 1994-08-09 | 1999-03-27 | Эйсай Ко., Лтд. | Конденсированный пиридазин или его фармакологически приемлемая соль, средство, проявляющее ингибирующую активность в отношении циклической гмф- фосфодиэстеразы |
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- 2005-08-31 US US11/660,748 patent/US7851472B2/en not_active Expired - Fee Related
- 2005-08-31 KR KR1020077006869A patent/KR101368093B1/ko not_active Expired - Fee Related
- 2005-08-31 ES ES05784647T patent/ES2347337T3/es not_active Expired - Lifetime
- 2005-08-31 JP JP2007528875A patent/JP5140427B2/ja not_active Expired - Fee Related
- 2005-08-31 EA EA200700537A patent/EA014324B1/ru not_active IP Right Cessation
- 2005-08-31 CA CA2578368A patent/CA2578368C/en not_active Expired - Fee Related
- 2005-08-31 CN CN200580038057XA patent/CN101133057B/zh not_active Expired - Fee Related
- 2005-08-31 WO PCT/EP2005/054266 patent/WO2006024640A2/en not_active Ceased
- 2005-08-31 AU AU2005279221A patent/AU2005279221C9/en not_active Ceased
- 2005-08-31 AT AT05784647T patent/ATE471324T1/de not_active IP Right Cessation
- 2005-08-31 NZ NZ553160A patent/NZ553160A/en not_active IP Right Cessation
- 2005-08-31 EP EP05784647A patent/EP1791543B1/en not_active Expired - Lifetime
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2007
- 2007-02-08 ZA ZA200701137A patent/ZA200701137B/xx unknown
- 2007-02-11 IL IL181271A patent/IL181271A/en not_active IP Right Cessation
- 2007-02-28 NO NO20071127A patent/NO20071127L/no not_active Application Discontinuation
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2010
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| RU2156252C2 (ru) * | 1994-09-16 | 2000-09-20 | Такеда Кемикал Индастриз, Лтд. | Триазолопиридазины, способ их получения, фармацевтические композиции на их основе и способ лечения |
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Also Published As
| Publication number | Publication date |
|---|---|
| IL181271A0 (en) | 2007-07-04 |
| NZ553160A (en) | 2010-08-27 |
| CN101133057A (zh) | 2008-02-27 |
| AU2005279221C9 (en) | 2012-08-23 |
| KR101368093B1 (ko) | 2014-03-14 |
| WO2006024640A2 (en) | 2006-03-09 |
| US20090005372A1 (en) | 2009-01-01 |
| EA200700537A1 (ru) | 2007-10-26 |
| DE602005021894D1 (de) | 2010-07-29 |
| AU2005279221C1 (en) | 2012-05-24 |
| IL181271A (en) | 2013-11-28 |
| ES2347337T3 (es) | 2010-10-28 |
| ZA200701137B (en) | 2008-11-26 |
| AU2005279221A1 (en) | 2006-03-09 |
| US20100286140A1 (en) | 2010-11-11 |
| US7851472B2 (en) | 2010-12-14 |
| BRPI0514586A (pt) | 2008-06-17 |
| CA2578368A1 (en) | 2006-03-09 |
| CA2578368C (en) | 2013-07-02 |
| EP1791543A2 (en) | 2007-06-06 |
| WO2006024640A3 (en) | 2007-06-07 |
| HK1115590A1 (en) | 2008-12-05 |
| JP2008511586A (ja) | 2008-04-17 |
| AU2005279221B2 (en) | 2011-10-13 |
| KR20070047834A (ko) | 2007-05-07 |
| ATE471324T1 (de) | 2010-07-15 |
| JP5140427B2 (ja) | 2013-02-06 |
| NO20071127L (no) | 2007-02-28 |
| CN101133057B (zh) | 2011-03-09 |
| EP1791543B1 (en) | 2010-06-16 |
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