CA1214168A - 6-substituted-s-triazole¬3,4-a|phthalazine derivatives - Google Patents
6-substituted-s-triazole¬3,4-a|phthalazine derivativesInfo
- Publication number
- CA1214168A CA1214168A CA000419398A CA419398A CA1214168A CA 1214168 A CA1214168 A CA 1214168A CA 000419398 A CA000419398 A CA 000419398A CA 419398 A CA419398 A CA 419398A CA 1214168 A CA1214168 A CA 1214168A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- phenyl
- compound
- substituted
- alkyl
- 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.)
- Expired
Links
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical class C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 title claims description 42
- 150000001875 compounds Chemical class 0.000 claims abstract description 129
- 238000000034 method Methods 0.000 claims abstract description 52
- -1 di (2-methoxyethyl) amino Chemical group 0.000 claims abstract description 41
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims abstract description 5
- JVJPJKLSGUJUJK-UHFFFAOYSA-N [1,2,4]triazolo[3,4-a]phthalazine Chemical class C1=CC=C2C=NN3C=NN=C3C2=C1 JVJPJKLSGUJUJK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 55
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 230000000875 corresponding effect Effects 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
- 229910052783 alkali metal Inorganic materials 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical class S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 150000002431 hydrogen Chemical group 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 239000002253 acid Chemical class 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 150000007857 hydrazones Chemical class 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- 239000007800 oxidant agent Substances 0.000 claims description 5
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
- 150000001299 aldehydes Chemical class 0.000 claims description 4
- 125000004685 alkoxythiocarbonyl group Chemical group 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000001301 oxygen Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- 229910052717 sulfur Chemical group 0.000 claims description 3
- 230000001131 transforming effect Effects 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 238000005660 chlorination reaction Methods 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 8
- 238000004519 manufacturing process Methods 0.000 claims 8
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims 2
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- IBZKBSXREAQDTO-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)ethanamine Chemical compound COCCNCCOC IBZKBSXREAQDTO-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 1
- 229910000062 azane Inorganic materials 0.000 claims 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 239000002249 anxiolytic agent Substances 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 99
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 239000000203 mixture Substances 0.000 description 37
- 235000019441 ethanol Nutrition 0.000 description 34
- 229960004756 ethanol Drugs 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 229960001701 chloroform Drugs 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 229960003529 diazepam Drugs 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 230000001143 conditioned effect Effects 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229960001407 sodium bicarbonate Drugs 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 150000004703 alkoxides Chemical class 0.000 description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- OZXCKWJNGZVAAJ-UHFFFAOYSA-N (4-phenylphthalazin-1-yl)hydrazine Chemical compound C12=CC=CC=C2C(NN)=NN=C1C1=CC=CC=C1 OZXCKWJNGZVAAJ-UHFFFAOYSA-N 0.000 description 4
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- PTIIJXOOYMMFJB-UHFFFAOYSA-N (6-chloro-4-phenylphthalazin-1-yl)hydrazine Chemical compound C12=CC(Cl)=CC=C2C(NN)=NN=C1C1=CC=CC=C1 PTIIJXOOYMMFJB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 102000004300 GABA-A Receptors Human genes 0.000 description 3
- 108090000839 GABA-A Receptors Proteins 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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
- 241000699670 Mus sp. Species 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 229910000831 Steel Inorganic materials 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 3
- 230000000049 anti-anxiety effect Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- 150000001557 benzodiazepines Chemical class 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 229940001584 sodium metabisulfite Drugs 0.000 description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000010959 steel Substances 0.000 description 3
- 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 2
- SGTXILTYXULEQD-UHFFFAOYSA-N 2H-triazolo[4,5-f]phthalazine Chemical group N1=NC=C2C3=NNN=C3C=CC2=C1 SGTXILTYXULEQD-UHFFFAOYSA-N 0.000 description 2
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- JCSFBTFUCJFIBS-UHFFFAOYSA-N [4-(4-methoxyphenyl)phthalazin-1-yl]hydrazine Chemical compound C1=CC(OC)=CC=C1C1=NN=C(NN)C2=CC=CC=C12 JCSFBTFUCJFIBS-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000009194 climbing Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- 235000013681 dietary sucrose Nutrition 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 125000001477 organic nitrogen group Chemical group 0.000 description 2
- 238000007243 oxidative cyclization reaction Methods 0.000 description 2
- 229960005152 pentetrazol Drugs 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
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- DQGFCLJXYFXXIJ-LFIBNONCSA-N budralazine Chemical compound C1=CC=C2C(N/N=C(C)/C=C(C)C)=NN=CC2=C1 DQGFCLJXYFXXIJ-LFIBNONCSA-N 0.000 description 1
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- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
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- VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
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- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
- 229960004535 oxazepam Drugs 0.000 description 1
- 230000021962 pH elevation Effects 0.000 description 1
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- IHRYNXNMVQFNPK-UHFFFAOYSA-N phthalazin-6-amine Chemical compound C1=NN=CC2=CC(N)=CC=C21 IHRYNXNMVQFNPK-UHFFFAOYSA-N 0.000 description 1
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- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
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- 230000001225 therapeutic effect Effects 0.000 description 1
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- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/34—Phthalazines with nitrogen atoms directly attached to carbon atoms of the nitrogen-containing ring, e.g. hydrazine radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Anesthesiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8201273 | 1982-01-18 | ||
| GB8201273 | 1982-01-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1214168A true CA1214168A (en) | 1986-11-18 |
Family
ID=10527683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000419398A Expired CA1214168A (en) | 1982-01-18 | 1983-01-13 | 6-substituted-s-triazole¬3,4-a|phthalazine derivatives |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4788186A (instruction) |
| EP (1) | EP0085840B1 (instruction) |
| JP (1) | JPS58124786A (instruction) |
| KR (1) | KR890000184B1 (instruction) |
| AT (1) | ATE22562T1 (instruction) |
| AU (1) | AU564026B2 (instruction) |
| CA (1) | CA1214168A (instruction) |
| DE (1) | DE3366494D1 (instruction) |
| DK (1) | DK163145C (instruction) |
| ES (1) | ES8601995A1 (instruction) |
| FI (1) | FI81350C (instruction) |
| GR (1) | GR78442B (instruction) |
| HU (1) | HU193033B (instruction) |
| IE (1) | IE55032B1 (instruction) |
| IL (1) | IL67697A (instruction) |
| NO (1) | NO161674C (instruction) |
| NZ (1) | NZ203021A (instruction) |
| PH (1) | PH21834A (instruction) |
| PT (1) | PT76107A (instruction) |
| ZA (1) | ZA83224B (instruction) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1194310B (it) * | 1983-07-12 | 1988-09-14 | Lepetit Spa | Derivati triazolo (3,4-a) ftalazinici 3,6-disostituiti |
| JP2000515851A (ja) * | 1996-07-25 | 2000-11-28 | メルク シヤープ エンド ドーム リミテツド | ＧＡＢＡ▲下Ａα５▼レセプターサブタイプの逆アゴニストとしての置換のあるトリアゾロピリダジン誘導体 |
| ES2194205T3 (es) * | 1996-07-25 | 2003-11-16 | Merck Sharp & Dohme | Derivados de triazolo-piridazina sustituidos como ligandos para los receptores gaba. |
| AU732455C (en) | 1997-05-08 | 2002-09-05 | Merck Sharp & Dohme Limited | Substituted 1,2,4-triazolo{3,4-a}phthalazine derivatives as gaba alpha 5 ligands |
| ES2137113B1 (es) * | 1997-07-29 | 2000-09-16 | Almirall Prodesfarma Sa | Nuevos derivados de triazolo-piridazinas heterociclicos. |
| GB9715977D0 (en) * | 1997-07-29 | 1997-10-01 | Merck Sharp & Dohme | Therapeutic agents |
| GB9726702D0 (en) * | 1997-12-18 | 1998-02-18 | Merck Sharp & Dohme | Therapeutic use |
| GB9723999D0 (en) | 1997-11-13 | 1998-01-14 | Merck Sharp & Dohme | Therapeutic use |
| WO1999025353A1 (en) * | 1997-11-13 | 1999-05-27 | Merck Sharp & Dohme Limited | Therapeutic uses of triazolo-pyridazine derivatives |
| GB9726699D0 (en) * | 1997-12-18 | 1998-02-18 | Merck Sharp & Dohme | Therapeutic use |
| GB9726701D0 (en) * | 1997-12-18 | 1998-02-18 | Merck Sharp & Dohme | Therapeutic use |
| US6110915A (en) * | 1997-12-18 | 2000-08-29 | Merck & Co., Inc. | Antiemetic use of triazolo-pyridazine derivatives |
| AU746866B2 (en) | 1998-01-14 | 2002-05-02 | Merck Sharp & Dohme Limited | Triazolo-pyridazine derivatives as ligands for GABA receptors |
| HUP0100575A3 (en) * | 1998-01-21 | 2003-03-28 | Merck Sharp & Dohme Ltd Hoddes | Triazolo-pyridazine derivatives as ligands for gaba receptors |
| GB9801234D0 (en) | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
| GB9801202D0 (en) | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
| GB9801208D0 (en) | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
| GB9801210D0 (en) * | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
| GB9801397D0 (en) | 1998-01-22 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
| GB9801538D0 (en) | 1998-01-23 | 1998-03-25 | Merck Sharp & Dohme | Pharmaceutical product |
| PL341975A1 (en) * | 1998-02-25 | 2001-05-07 | Merck Sharp & Dohme | Substituted 1,2,4-triazole[3,4-a]phtalazine |
| EE200000514A (et) | 1998-02-25 | 2002-02-15 | Merck Sharp & Dohme Limited | Asendatud triasolopüridasiini derivaat, seda sisaldav farmatseutiline kompositsioon ning selle kasutamine kognitsioonivõimet suurendava ravimi valmistamiseks |
| GB9824897D0 (en) | 1998-11-12 | 1999-01-06 | Merck Sharp & Dohme | Therapeutic compounds |
| WO2000027849A2 (en) | 1998-11-12 | 2000-05-18 | Merck & Co., Inc. | Therapeutic polymorphs of a gaba-a alpha-5 inverse agonist and pamoate formulations of the same |
| GB9929569D0 (en) * | 1999-12-14 | 2000-02-09 | Merck Sharp & Dohme | Therapeutic agents |
| GB0028583D0 (en) | 2000-11-23 | 2001-01-10 | Merck Sharp & Dohme | Therapeutic compounds |
| CA2442264A1 (en) * | 2001-04-10 | 2002-10-24 | Merck & Co., Inc. | A method of treating cancer |
| US6958334B2 (en) * | 2001-04-10 | 2005-10-25 | Merck & Co., Inc. | Inhibitors of Akt activity |
| WO2003084473A2 (en) * | 2002-04-08 | 2003-10-16 | Merck & Co., Inc. | Method of treating cancer |
| US20050054647A1 (en) * | 2002-12-27 | 2005-03-10 | Detlev Schuppan | New pharmaceutical combination |
| NZ553160A (en) * | 2004-09-02 | 2010-08-27 | Nycomed Gmbh | Anilino-substituted triazolophthalazine derivatives having PDE2 inhibitory activity |
| EP1836207B1 (en) * | 2005-01-05 | 2012-10-10 | Nycomed GmbH | Triazolophthalazines as pde2-inhibitors |
| WO2006072612A2 (en) * | 2005-01-05 | 2006-07-13 | Nycomed Gmbh | Triazolophthalazines as pde2- inhibitors |
| PH12012501361A1 (en) | 2009-12-31 | 2012-10-22 | Centro Nac De Investigaciones Oncologicas Cnio | Tricyclic compounds for use as kinase inhibitors |
| CN103694244B (zh) * | 2014-01-09 | 2016-03-30 | 郑州大学 | 3,6位取代-1,2,4-三氮唑并[3,4-a]酞嗪类化合物及其制备和用途 |
| CN104016986B (zh) * | 2014-03-13 | 2016-02-03 | 郑州大学 | 3-取代-6-(1-取代哌嗪基)-1,2,4-三氮唑并[3,4-a]酞嗪类化合物、其制备方法和用途 |
| EP4279074A1 (en) * | 2022-05-19 | 2023-11-22 | Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts, Universitätsmedizin | Azolo compounds for treatment of fibrotic diseases |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2484029A (en) * | 1945-12-21 | 1949-10-11 | Ciba Pharm Prod Inc | Hydrazine derivatives of pyridazine compounds |
| GB629177A (en) * | 1945-12-21 | 1949-09-14 | Ciba Ltd | Manufacture of new hydrazine compounds and derivatives thereof |
| JPS5132598A (en) * | 1974-09-13 | 1976-03-19 | Eisai Co Ltd | Toriazoro * 3 44 ee * futarajinjudotai no goseiho |
| JPS603080B2 (ja) * | 1976-08-10 | 1985-01-25 | 三菱化学株式会社 | Ｓ―トリアゾロ〔３，４ ―α〕〔５，６，７，８〕テトラヒドロ フタラジン類 |
| GR70309B (instruction) * | 1979-10-29 | 1982-09-08 | Dow Chemical Co |
-
1983
- 1983-01-12 FI FI830100A patent/FI81350C/fi not_active IP Right Cessation
- 1983-01-12 PH PH28380A patent/PH21834A/en unknown
- 1983-01-13 CA CA000419398A patent/CA1214168A/en not_active Expired
- 1983-01-13 DE DE8383100232T patent/DE3366494D1/de not_active Expired
- 1983-01-13 NZ NZ203021A patent/NZ203021A/en unknown
- 1983-01-13 ZA ZA83224A patent/ZA83224B/xx unknown
- 1983-01-13 AT AT83100232T patent/ATE22562T1/de not_active IP Right Cessation
- 1983-01-13 GR GR70257A patent/GR78442B/el unknown
- 1983-01-13 EP EP83100232A patent/EP0085840B1/en not_active Expired
- 1983-01-14 NO NO830110A patent/NO161674C/no unknown
- 1983-01-17 HU HU83141A patent/HU193033B/hu not_active IP Right Cessation
- 1983-01-17 IL IL67697A patent/IL67697A/xx unknown
- 1983-01-17 IE IE82/83A patent/IE55032B1/en not_active IP Right Cessation
- 1983-01-18 KR KR1019830000174A patent/KR890000184B1/ko not_active Expired
- 1983-01-18 DK DK017983A patent/DK163145C/da not_active IP Right Cessation
- 1983-01-18 AU AU10550/83A patent/AU564026B2/en not_active Ceased
- 1983-01-18 JP JP58005413A patent/JPS58124786A/ja active Granted
- 1983-01-18 PT PT76107A patent/PT76107A/pt unknown
-
1984
- 1984-04-10 ES ES531458A patent/ES8601995A1/es not_active Expired
-
1987
- 1987-10-20 US US07/112,015 patent/US4788186A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US4788186A (en) | 1988-11-29 |
| EP0085840A1 (en) | 1983-08-17 |
| AU1055083A (en) | 1983-07-28 |
| JPH048428B2 (instruction) | 1992-02-17 |
| DK17983A (da) | 1983-07-19 |
| DK17983D0 (da) | 1983-01-18 |
| KR840003254A (ko) | 1984-08-20 |
| ES531458A0 (es) | 1985-11-01 |
| ES8601995A1 (es) | 1985-11-01 |
| AU564026B2 (en) | 1987-07-30 |
| JPS58124786A (ja) | 1983-07-25 |
| PT76107A (en) | 1983-02-01 |
| FI830100A0 (fi) | 1983-01-12 |
| DE3366494D1 (de) | 1986-11-06 |
| NO830110L (no) | 1983-07-19 |
| GR78442B (instruction) | 1984-09-27 |
| DK163145C (da) | 1992-06-22 |
| FI81350C (fi) | 1990-10-10 |
| EP0085840B1 (en) | 1986-10-01 |
| IE55032B1 (en) | 1990-05-09 |
| NO161674C (no) | 1989-09-13 |
| ATE22562T1 (de) | 1986-10-15 |
| ZA83224B (en) | 1983-10-26 |
| IL67697A0 (en) | 1983-05-15 |
| IL67697A (en) | 1990-02-09 |
| NO161674B (no) | 1989-06-05 |
| IE830082L (en) | 1983-07-18 |
| KR890000184B1 (ko) | 1989-03-09 |
| HU193033B (en) | 1987-08-28 |
| FI830100L (fi) | 1983-07-19 |
| FI81350B (fi) | 1990-06-29 |
| DK163145B (da) | 1992-01-27 |
| PH21834A (en) | 1988-03-17 |
| NZ203021A (en) | 1986-05-09 |
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