JPS58124786A - 新規な６−置換−ｓ−トリアゾロ〔３，４−ａ〕フタラジン誘導体 - Google Patents
新規な６−置換−ｓ−トリアゾロ〔３，４−ａ〕フタラジン誘導体Info
- Publication number
- JPS58124786A JPS58124786A JP58005413A JP541383A JPS58124786A JP S58124786 A JPS58124786 A JP S58124786A JP 58005413 A JP58005413 A JP 58005413A JP 541383 A JP541383 A JP 541383A JP S58124786 A JPS58124786 A JP S58124786A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- phenyl
- substituted
- alkyl
- alkoxy
- 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.)
- Granted
Links
- -1 6-substituted-s-triazolo(3,4-a)phthalazine Chemical class 0.000 title claims description 33
- 238000000034 method Methods 0.000 claims abstract description 41
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 129
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 125000003545 alkoxy group Chemical group 0.000 claims description 50
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 41
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 13
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims description 12
- 229910052783 alkali metal Inorganic materials 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 150000007857 hydrazones Chemical class 0.000 claims description 8
- 239000007800 oxidant agent Substances 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 150000004703 alkoxides Chemical class 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 239000002249 anxiolytic agent Substances 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 4
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000004020 conductor Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 238000007796 conventional method Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000012467 final product Substances 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 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 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 150000001351 alkyl iodides Chemical class 0.000 claims description 2
- 238000005660 chlorination reaction Methods 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 241000270708 Testudinidae Species 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 claims 1
- 238000010030 laminating Methods 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 6
- 230000008569 process Effects 0.000 abstract description 3
- 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 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 149
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 238000002844 melting Methods 0.000 description 36
- 230000008018 melting Effects 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000000047 product Substances 0.000 description 14
- 238000002425 crystallisation Methods 0.000 description 13
- 230000008025 crystallization Effects 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 8
- OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003960 organic solvent Substances 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
- 230000001143 conditioned effect Effects 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 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
- 238000010438 heat treatment Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical compound C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 102000004300 GABA-A Receptors Human genes 0.000 description 3
- 108090000839 GABA-A Receptors Proteins 0.000 description 3
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001340 alkali metals Chemical group 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000002585 base Substances 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
- 239000002775 capsule Substances 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 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
- 239000012141 concentrate Substances 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229960003529 diazepam Drugs 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000002474 experimental method Methods 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
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- KHIILJVSYUGMSE-UHFFFAOYSA-N 1-phenylphthalazine Chemical compound C1=CC=CC=C1C1=NN=CC2=CC=CC=C12 KHIILJVSYUGMSE-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
- 241000894006 Bacteria Species 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 241000243251 Hydra Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 description 2
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 150000001557 benzodiazepines Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 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
- 229940099112 cornstarch Drugs 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
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 125000001477 organic nitrogen group Chemical group 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000007243 oxidative cyclization reaction Methods 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 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 1
- 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 1
- 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 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- QBELEDRHMPMKHP-UHFFFAOYSA-N 1-bromo-2-chlorobenzene Chemical compound ClC1=CC=CC=C1Br QBELEDRHMPMKHP-UHFFFAOYSA-N 0.000 description 1
- SJBXMBRSTWBJRN-UHFFFAOYSA-N 2-benzoyl-4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 SJBXMBRSTWBJRN-UHFFFAOYSA-N 0.000 description 1
- UYCUMNRCCJNSBR-UHFFFAOYSA-N 2-ethoxy-2-oxoacetic acid;hydrochloride Chemical compound Cl.CCOC(=O)C(O)=O UYCUMNRCCJNSBR-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical group CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- SGTXILTYXULEQD-UHFFFAOYSA-N 2H-triazolo[4,5-f]phthalazine Chemical group N1=NC=C2C3=NNN=C3C=CC2=C1 SGTXILTYXULEQD-UHFFFAOYSA-N 0.000 description 1
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- 238000004364 calculation method Methods 0.000 description 1
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- 241001233037 catfish Species 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
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- 210000000078 claw Anatomy 0.000 description 1
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- 229940125904 compound 1 Drugs 0.000 description 1
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- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
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- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 1
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- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- OPXNFHAILOHHFO-UHFFFAOYSA-N ethyl 4-chlorobutanoate Chemical compound CCOC(=O)CCCCl OPXNFHAILOHHFO-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
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- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
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- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 210000000554 iris Anatomy 0.000 description 1
- QBYJBZPUGVGKQQ-DIFDVCDBSA-N isodrin Chemical compound C1[C@@H]2C=C[C@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-DIFDVCDBSA-N 0.000 description 1
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- ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
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- 150000007522 mineralic acids Chemical class 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
- 150000004767 nitrides Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- ZERJNAGZUCPHNB-UHFFFAOYSA-N tetrazane Chemical compound NNNN ZERJNAGZUCPHNB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
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 (2)
| Publication Number | Publication Date |
|---|---|
| JPS58124786A true JPS58124786A (ja) | 1983-07-25 |
| JPH048428B2 JPH048428B2 (en, 2012) | 1992-02-17 |
Family
ID=10527683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58005413A Granted JPS58124786A (ja) | 1982-01-18 | 1983-01-18 | 新規な６−置換−ｓ−トリアゾロ〔３，４−ａ〕フタラジン誘導体 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4788186A (en, 2012) |
| EP (1) | EP0085840B1 (en, 2012) |
| JP (1) | JPS58124786A (en, 2012) |
| KR (1) | KR890000184B1 (en, 2012) |
| AT (1) | ATE22562T1 (en, 2012) |
| AU (1) | AU564026B2 (en, 2012) |
| CA (1) | CA1214168A (en, 2012) |
| DE (1) | DE3366494D1 (en, 2012) |
| DK (1) | DK163145C (en, 2012) |
| ES (1) | ES531458A0 (en, 2012) |
| FI (1) | FI81350C (en, 2012) |
| GR (1) | GR78442B (en, 2012) |
| HU (1) | HU193033B (en, 2012) |
| IE (1) | IE55032B1 (en, 2012) |
| IL (1) | IL67697A (en, 2012) |
| NO (1) | NO161674C (en, 2012) |
| NZ (1) | NZ203021A (en, 2012) |
| PH (1) | PH21834A (en, 2012) |
| PT (1) | PT76107A (en, 2012) |
| ZA (1) | ZA83224B (en, 2012) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001525802A (ja) * | 1997-05-08 | 2001-12-11 | メルク シヤープ エンド ドーム リミテツド | ＧＡＢＡα５リガンドとしての置換１，２，４−トリアゾロ［３，４−ａ］フタラジン誘導体 |
| JP2008526716A (ja) * | 2005-01-05 | 2008-07-24 | 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 |
| JP2008526717A (ja) * | 2005-01-05 | 2008-07-24 | 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 |
Families Citing this family (34)
| 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 |
| YU2899A (sh) * | 1996-07-25 | 2000-03-21 | Merck Sharp & Dohme Limited | Supstituisani triazolo-piridazin derivati kao ligandi za gaba receptore |
| 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 |
| 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 |
| GB9726702D0 (en) * | 1997-12-18 | 1998-02-18 | Merck Sharp & Dohme | Therapeutic use |
| AU1041599A (en) * | 1997-11-13 | 1999-06-07 | Jose Luis Castro Pineiro | Therapeutic uses of triazolo-pyridazine derivatives |
| GB9723999D0 (en) | 1997-11-13 | 1998-01-14 | Merck Sharp & Dohme | Therapeutic use |
| US6110915A (en) * | 1997-12-18 | 2000-08-29 | Merck & Co., Inc. | Antiemetic use of triazolo-pyridazine derivatives |
| WO1999036423A1 (en) * | 1998-01-14 | 1999-07-22 | Merck Sharp & Dohme Limited | Triazolo-pyridazine derivatives as ligands for gaba receptors |
| 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 |
| GB9801234D0 (en) | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
| IL136442A0 (en) * | 1998-01-21 | 2001-06-14 | Merck Sharp & Dohme | Triazolo-pyridazine derivatives as ligands for gaba receptors |
| 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 |
| CZ291302B6 (cs) | 1998-02-25 | 2003-01-15 | Merck Sharp & Dohme Limited | Substituovaný 1,2,4-triazolo[3,4-a]ftalazinový derivát |
| JP2002504554A (ja) * | 1998-02-25 | 2002-02-12 | メルク シャープ エンド ドーム リミテッド | 置換１，２，４−トリアゾロ［３，４−ａ］ピリダジン |
| GB9824897D0 (en) | 1998-11-12 | 1999-01-06 | Merck Sharp & Dohme | Therapeutic compounds |
| JP2002529468A (ja) | 1998-11-12 | 2002-09-10 | メルク エンド カムパニー インコーポレーテッド | ＧＡＢＡ−Ａα−５逆活性薬の治療性多形およびそのパモエート組成物 |
| 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 |
| EP1496981A2 (en) * | 2002-04-08 | 2005-01-19 | Merck & Co., Inc. | Method of treating cancer |
| US20050054647A1 (en) * | 2002-12-27 | 2005-03-10 | Detlev Schuppan | New pharmaceutical combination |
| JP5140427B2 (ja) * | 2004-09-02 | 2013-02-06 | 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 |
| 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 (en, 2012) * | 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 EP EP83100232A patent/EP0085840B1/en not_active Expired
- 1983-01-13 CA CA000419398A patent/CA1214168A/en not_active Expired
- 1983-01-13 GR GR70257A patent/GR78442B/el unknown
- 1983-01-13 NZ NZ203021A patent/NZ203021A/en unknown
- 1983-01-13 DE DE8383100232T patent/DE3366494D1/de not_active Expired
- 1983-01-13 AT AT83100232T patent/ATE22562T1/de not_active IP Right Cessation
- 1983-01-13 ZA ZA83224A patent/ZA83224B/xx unknown
- 1983-01-14 NO NO830110A patent/NO161674C/no unknown
- 1983-01-17 IE IE82/83A patent/IE55032B1/en not_active IP Right Cessation
- 1983-01-17 IL IL67697A patent/IL67697A/xx unknown
- 1983-01-17 HU HU83141A patent/HU193033B/hu not_active IP Right Cessation
- 1983-01-18 AU AU10550/83A patent/AU564026B2/en not_active Ceased
- 1983-01-18 DK DK017983A patent/DK163145C/da not_active IP Right Cessation
- 1983-01-18 PT PT76107A patent/PT76107A/pt unknown
- 1983-01-18 JP JP58005413A patent/JPS58124786A/ja active Granted
- 1983-01-18 KR KR1019830000174A patent/KR890000184B1/ko not_active Expired
-
1984
- 1984-04-10 ES ES531458A patent/ES531458A0/es active Granted
-
1987
- 1987-10-20 US US07/112,015 patent/US4788186A/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001525802A (ja) * | 1997-05-08 | 2001-12-11 | メルク シヤープ エンド ドーム リミテツド | ＧＡＢＡα５リガンドとしての置換１，２，４−トリアゾロ［３，４−ａ］フタラジン誘導体 |
| JP2008526716A (ja) * | 2005-01-05 | 2008-07-24 | 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 |
| JP2008526717A (ja) * | 2005-01-05 | 2008-07-24 | 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| NO161674B (no) | 1989-06-05 |
| IL67697A (en) | 1990-02-09 |
| NZ203021A (en) | 1986-05-09 |
| ATE22562T1 (de) | 1986-10-15 |
| NO830110L (no) | 1983-07-19 |
| HU193033B (en) | 1987-08-28 |
| NO161674C (no) | 1989-09-13 |
| DK163145B (da) | 1992-01-27 |
| IE830082L (en) | 1983-07-18 |
| CA1214168A (en) | 1986-11-18 |
| KR840003254A (ko) | 1984-08-20 |
| DE3366494D1 (de) | 1986-11-06 |
| IL67697A0 (en) | 1983-05-15 |
| ZA83224B (en) | 1983-10-26 |
| FI830100A0 (fi) | 1983-01-12 |
| FI81350C (fi) | 1990-10-10 |
| JPH048428B2 (en, 2012) | 1992-02-17 |
| DK17983D0 (da) | 1983-01-18 |
| IE55032B1 (en) | 1990-05-09 |
| PH21834A (en) | 1988-03-17 |
| AU1055083A (en) | 1983-07-28 |
| FI81350B (fi) | 1990-06-29 |
| DK163145C (da) | 1992-06-22 |
| US4788186A (en) | 1988-11-29 |
| EP0085840A1 (en) | 1983-08-17 |
| GR78442B (en, 2012) | 1984-09-27 |
| KR890000184B1 (ko) | 1989-03-09 |
| PT76107A (en) | 1983-02-01 |
| AU564026B2 (en) | 1987-07-30 |
| DK17983A (da) | 1983-07-19 |
| ES8601995A1 (es) | 1985-11-01 |
| FI830100L (fi) | 1983-07-19 |
| EP0085840B1 (en) | 1986-10-01 |
| ES531458A0 (es) | 1985-11-01 |
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