DE3008632C2 - - Google Patents
Info
- Publication number
- DE3008632C2 DE3008632C2 DE3008632A DE3008632A DE3008632C2 DE 3008632 C2 DE3008632 C2 DE 3008632C2 DE 3008632 A DE3008632 A DE 3008632A DE 3008632 A DE3008632 A DE 3008632A DE 3008632 C2 DE3008632 C2 DE 3008632C2
- Authority
- DE
- Germany
- Prior art keywords
- indole
- imidazolylmethyl
- lower alkyl
- solution
- mixture
- 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
- 150000001875 compounds Chemical class 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- -1 R2hydrogen Chemical group 0.000 claims description 17
- 108010069102 Thromboxane-A synthase Proteins 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 108010064377 prostacyclin synthetase Proteins 0.000 claims description 9
- 230000009471 action Effects 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims description 7
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- KPYVDNYEILVGAJ-UHFFFAOYSA-N 3-[3-(1H-imidazol-2-ylmethyl)-2-methylindol-1-yl]propanoic acid Chemical compound C(=O)(O)CCN1C(=C(C2=CC=CC=C12)CC=1NC=CN=1)C KPYVDNYEILVGAJ-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 239000000203 mixture Substances 0.000 description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 20
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 229960001123 epoprostenol Drugs 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 14
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 208000019695 Migraine disease Diseases 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 235000011087 fumaric acid Nutrition 0.000 description 6
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000002792 vascular Effects 0.000 description 6
- GYLUOCFMFMJROH-UHFFFAOYSA-N 3-(1h-imidazol-2-ylmethyl)-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1CC1=NC=CN1 GYLUOCFMFMJROH-UHFFFAOYSA-N 0.000 description 5
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 5
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 5
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000001530 fumaric acid Substances 0.000 description 5
- 206010027599 migraine Diseases 0.000 description 5
- 150000003180 prostaglandins Chemical class 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- OLWCXDSZSGVCAS-UHFFFAOYSA-N 2-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]acetic acid Chemical compound C12=CC=CC=C2N(CC(=O)O)C=C1CC1=NC=CN1 OLWCXDSZSGVCAS-UHFFFAOYSA-N 0.000 description 4
- KPPJRNUWGDJZEI-UHFFFAOYSA-N 4-[[3-(1h-imidazol-2-ylmethyl)indol-1-yl]methyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CN1C2=CC=CC=C2C(CC=2NC=CN=2)=C1 KPPJRNUWGDJZEI-UHFFFAOYSA-N 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 206010019233 Headaches Diseases 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- MMTQOPYULGPLGP-UHFFFAOYSA-N ethyl 2-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]acetate Chemical compound C12=CC=CC=C2N(CC(=O)OCC)C=C1CC1=NC=CN1 MMTQOPYULGPLGP-UHFFFAOYSA-N 0.000 description 4
- 231100000869 headache Toxicity 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000012265 solid product Substances 0.000 description 4
- AQVTZBHZFUIILH-UHFFFAOYSA-N 3-indol-1-ylpropanenitrile Chemical class C1=CC=C2N(CCC#N)C=CC2=C1 AQVTZBHZFUIILH-UHFFFAOYSA-N 0.000 description 3
- JEQKWIQAHBZXGN-UHFFFAOYSA-N 4-[[3-(1h-imidazol-2-ylmethyl)indol-1-yl]methyl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1CN1C2=CC=CC=C2C(CC=2NC=CN=2)=C1 JEQKWIQAHBZXGN-UHFFFAOYSA-N 0.000 description 3
- AYGFLNDNSWHEQD-UHFFFAOYSA-N 4-[[3-(1h-imidazol-2-ylmethyl)indol-1-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1C2=CC=CC=C2C(CC=2NC=CN=2)=C1 AYGFLNDNSWHEQD-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000003960 Ligases Human genes 0.000 description 3
- 108090000364 Ligases Proteins 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000003973 alkyl amines Chemical class 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 229940114079 arachidonic acid Drugs 0.000 description 3
- 235000021342 arachidonic acid Nutrition 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 230000008859 change Effects 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
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 210000001589 microsome Anatomy 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- MBGGBVCUIVRRBF-UHFFFAOYSA-N sulfinpyrazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 description 3
- 229960003329 sulfinpyrazone Drugs 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 3
- FJILNCBFUJUAEP-WLHGVMLRSA-N (e)-but-2-enedioic acid;3-[3-(1-imidazol-1-ylethyl)indol-1-yl]propanenitrile Chemical compound OC(=O)\C=C\C(O)=O.C=1N(CCC#N)C2=CC=CC=C2C=1C(C)N1C=CN=C1 FJILNCBFUJUAEP-WLHGVMLRSA-N 0.000 description 2
- NGAGGQFPPLZNBD-WLHGVMLRSA-N (e)-but-2-enedioic acid;3-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]propanenitrile Chemical compound OC(=O)\C=C\C(O)=O.C12=CC=CC=C2N(CCC#N)C=C1CC1=NC=CN1 NGAGGQFPPLZNBD-WLHGVMLRSA-N 0.000 description 2
- GMENRYHNSQKRLR-JITBQSAISA-N (e)-but-2-enedioic acid;3-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]propanoic acid;hydrate Chemical compound O.OC(=O)\C=C\C(O)=O.C12=CC=CC=C2N(CCC(=O)O)C=C1CC1=NC=CN1 GMENRYHNSQKRLR-JITBQSAISA-N 0.000 description 2
- UJUGIDKMUFPYHC-WLHGVMLRSA-N (e)-but-2-enedioic acid;ethyl 4-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]butanoate Chemical compound OC(=O)\C=C\C(O)=O.C12=CC=CC=C2N(CCCC(=O)OCC)C=C1CC1=NC=CN1 UJUGIDKMUFPYHC-WLHGVMLRSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- QGXNHCXKWFNKCG-UHFFFAOYSA-N 2-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC=C1C#N QGXNHCXKWFNKCG-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- RTMPJTRCJABAMV-UHFFFAOYSA-N 2-[3-(1h-imidazol-2-ylmethyl)-1h-indol-2-yl]propanenitrile Chemical compound N#CC(C)C=1NC2=CC=CC=C2C=1CC1=NC=CN1 RTMPJTRCJABAMV-UHFFFAOYSA-N 0.000 description 2
- SWAPJEUGWQSFJX-UHFFFAOYSA-N 2-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]acetamide Chemical compound C12=CC=CC=C2N(CC(=O)N)C=C1CC1=NC=CN1 SWAPJEUGWQSFJX-UHFFFAOYSA-N 0.000 description 2
- NDLQIWJGAXPIQZ-UHFFFAOYSA-N 2-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]ethanol Chemical compound C12=CC=CC=C2N(CCO)C=C1CC1=NC=CN1 NDLQIWJGAXPIQZ-UHFFFAOYSA-N 0.000 description 2
- KHIKPAVBCWEWLG-UHFFFAOYSA-N 3-(1h-imidazol-2-ylmethyl)-1-[2-(2h-tetrazol-5-yl)ethyl]indole Chemical compound N1=NNN=C1CCN(C1=CC=CC=C11)C=C1CC1=NC=CN1 KHIKPAVBCWEWLG-UHFFFAOYSA-N 0.000 description 2
- SZICIHMAKAMELL-UHFFFAOYSA-N 3-(1h-imidazol-2-ylmethyl)-1-[[4-(2h-tetrazol-5-yl)phenyl]methyl]indole Chemical compound C=1N(CC=2C=CC(=CC=2)C2=NNN=N2)C2=CC=CC=C2C=1CC1=NC=CN1 SZICIHMAKAMELL-UHFFFAOYSA-N 0.000 description 2
- NWTSCLIQSBYDMR-UHFFFAOYSA-N 3-(1h-imidazol-2-ylmethyl)-5-methoxy-1h-indole Chemical compound C12=CC(OC)=CC=C2NC=C1CC1=NC=CN1 NWTSCLIQSBYDMR-UHFFFAOYSA-N 0.000 description 2
- FGTKEKMWUHXOEB-UHFFFAOYSA-N 3-[3-(1h-imidazol-2-ylmethyl)-2-propan-2-ylindol-1-yl]propanamide Chemical compound C12=CC=CC=C2N(CCC(N)=O)C(C(C)C)=C1CC1=NC=CN1 FGTKEKMWUHXOEB-UHFFFAOYSA-N 0.000 description 2
- LCNLDGYZJLITHP-UHFFFAOYSA-N 3-[3-(1h-imidazol-2-ylmethyl)-5-methoxyindol-1-yl]propanenitrile Chemical compound C12=CC(OC)=CC=C2N(CCC#N)C=C1CC1=NC=CN1 LCNLDGYZJLITHP-UHFFFAOYSA-N 0.000 description 2
- UMMBPBWIKJVQHJ-UHFFFAOYSA-N 3-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]-n-phenylpropanamide Chemical compound C=1C=CC=CC=1NC(=O)CCN(C1=CC=CC=C11)C=C1CC1=NC=CN1 UMMBPBWIKJVQHJ-UHFFFAOYSA-N 0.000 description 2
- PCYRLLSTOAPEHH-UHFFFAOYSA-N 3-[3-(1h-imidazol-2-ylmethyl)indol-1-yl]propanoic acid Chemical compound C12=CC=CC=C2N(CCC(=O)O)C=C1CC1=NC=CN1 PCYRLLSTOAPEHH-UHFFFAOYSA-N 0.000 description 2
- IAJMSSVNFLHCPF-UHFFFAOYSA-N 3-[[3-(1h-imidazol-2-ylmethyl)indol-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2C3=CC=CC=C3C(CC=3NC=CN=3)=C2)=C1 IAJMSSVNFLHCPF-UHFFFAOYSA-N 0.000 description 2
- FRXJYUFHAXXSAL-UHFFFAOYSA-N 3-chloro-n-phenylpropanamide Chemical compound ClCCC(=O)NC1=CC=CC=C1 FRXJYUFHAXXSAL-UHFFFAOYSA-N 0.000 description 2
- YUYWOJYXRRBNGX-UHFFFAOYSA-N 5-chloro-3-(1h-imidazol-2-ylmethyl)-1h-indole Chemical compound C12=CC(Cl)=CC=C2NC=C1CC1=NC=CN1 YUYWOJYXRRBNGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-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
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
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- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7908123 | 1979-03-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3008632A1 DE3008632A1 (de) | 1980-10-16 |
| DE3008632C2 true DE3008632C2 (enExample) | 1988-02-25 |
Family
ID=10503707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19803008632 Granted DE3008632A1 (de) | 1979-03-07 | 1980-03-06 | Indol-derivate, verfahren zu ihrer herstellung und ihre verwendung |
Country Status (36)
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4414159A (en) * | 1980-09-26 | 1983-11-08 | E. I. Du Pont De Nemours & Co. | Vinyl ether monomers and polymers therefrom |
| US4444775A (en) * | 1981-06-22 | 1984-04-24 | Ciba-Geigy Corporation | Substituted imidazo[1,5-A]pyridines |
| KR840000529A (ko) * | 1981-07-07 | 1984-02-25 | 콘스탄틴 루이스 클레멘트 | 인돌 유도체의 제조방법 |
| ZA825413B (en) * | 1981-08-26 | 1983-06-29 | Pfizer | Thromboxane synthetase inhibitors, processes for their production, and pharmaceutical compositions comprising them |
| US4478842A (en) * | 1981-11-19 | 1984-10-23 | Ciba-Geigy Corporation | N-Substituted-2-pyridylindoles |
| US4460777A (en) * | 1981-11-19 | 1984-07-17 | Ciba-Geigy Corporation | N-Substituted-2-pyridylindoles |
| US4539410A (en) * | 1982-09-30 | 1985-09-03 | Ciba-Geigy Corporation | N-Substituted-2-(1-imidazolyl)indoles |
| US4436746A (en) | 1982-09-30 | 1984-03-13 | Ciba-Geigy Corporation | Thromboxane synthetase inhibitory N-substituted-2-(1-imidazolyl)indoles |
| AT376436B (de) * | 1982-11-05 | 1984-11-26 | Laevosan Gmbh & Co Kg | Verfahren zur herstellung neuer thiophen-2carbons[urederivate und pharmazeutisch vertraeglicher saeure- oder basenadditionssalze davon |
| US4511573A (en) * | 1983-05-17 | 1985-04-16 | Ciba-Geigy Corporation | 3-Substituted-2-(heteroaryl) indoles |
| ATE90076T1 (de) | 1986-03-27 | 1993-06-15 | Merck Frosst Canada Inc | Tetrahydrocarbazole ester. |
| JPH0832679B2 (ja) * | 1986-09-05 | 1996-03-29 | 理化学研究所 | Ｎ―フタルイシド誘導体及びその製造法 |
| GR871809B (en) * | 1986-11-28 | 1988-03-07 | Glaxo Group Ltd | Process for the preparation of tricyclic ketones |
| KR920700210A (ko) * | 1989-03-31 | 1992-02-19 | 기따미 가즈히꼬 | 신규 이미다졸 유도체, 그의 제법 및 그의 의약용도 |
| ATE204275T1 (de) * | 1990-06-07 | 2001-09-15 | Astrazeneca Ab | Indolderivate als 5-ht1-like agonisten |
| DE4023215A1 (de) * | 1990-07-21 | 1992-01-23 | Hoechst Ag | Substituierte azole, verfahren zu deren herstellung, sie enthaltende mittel und deren verwendung |
| KR930702334A (ko) * | 1990-09-13 | 1993-09-08 | 데이비드 로버트 | 5 하이드록시트립타민 수용체 길항제로서의 인돌우레아 |
| US5162337A (en) * | 1990-10-05 | 1992-11-10 | Merck & Co., Inc. | Animal growth promotion |
| US5120749A (en) * | 1991-02-20 | 1992-06-09 | Abbott Laboratories | Platelet activating antagonists |
| AU671092B2 (en) * | 1991-12-18 | 1996-08-15 | Schering Corporation | Imidazolyl or imidazoylalkyl substituted with a four or five membered nitrogen containing heterocyclic ring |
| US5538973A (en) * | 1992-03-27 | 1996-07-23 | Kyoto Pharmaceutical Industries, Ltd. | Imidazole derivative, pharmaceutical use thereof, and intermediate therefor |
| AU658729B2 (en) * | 1992-03-27 | 1995-04-27 | Kyoto Pharmaceutical Industries, Ltd. | 3-(1H-imidazol-1-ylmethyl)-1H-indole derivatives |
| JPH0632913U (ja) * | 1992-09-18 | 1994-04-28 | 三洋電機株式会社 | 床暖房用パネル |
| SK7522001A3 (en) * | 1998-03-31 | 2002-02-05 | Inst For Pharm Discovery Inc | Substituted indolealkanoic acids |
| ATE345340T1 (de) * | 2002-09-12 | 2006-12-15 | Hoffmann La Roche | N-substituierte-1h-indol-5-propansäure verbindungen als ppar-agonisten zur behandlung von diabetis |
| AU2003292030B2 (en) * | 2002-11-25 | 2007-01-04 | F. Hoffmann-La Roche Ag | Indolyl derivatives |
| US7348351B2 (en) * | 2002-12-10 | 2008-03-25 | Wyeth | Substituted 3-alkyl and 3-arylalkyl 1H-indol-1yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1) |
| GB0324763D0 (en) * | 2003-10-23 | 2003-11-26 | Oxagen Ltd | Use of compounds in therapy |
| PL1756096T3 (pl) * | 2004-05-03 | 2010-01-29 | Hoffmann La Roche | Pochodne indolilowe jako modulatory wątrobowych receptorów X |
| MX2007004525A (es) * | 2004-10-12 | 2007-09-19 | Decode Genetics Inc | Sulfonamidas biciclicas peri-sustituidas para enfermedad de arteria oclusiva. |
| WO2007024944A1 (en) * | 2005-08-25 | 2007-03-01 | Schering Corporation | Imidazole derivatives as functionally selective alpha2c adrenoreceptor agonists |
| GB2431927B (en) * | 2005-11-04 | 2010-03-17 | Amira Pharmaceuticals Inc | 5-Lipoxygenase-activating protein (FLAP) inhibitors |
| US8399666B2 (en) * | 2005-11-04 | 2013-03-19 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| US7977359B2 (en) * | 2005-11-04 | 2011-07-12 | Amira Pharmaceuticals, Inc. | 5-lipdxygenase-activating protein (FLAP) inhibitors |
| RU2008149518A (ru) * | 2006-05-16 | 2010-06-27 | Декод Дженетикс, Ехф. (Is) | Способ получения 7-(акрилоил) индолов |
| AU2007279079A1 (en) | 2006-07-22 | 2008-01-31 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
| TW200920369A (en) * | 2007-10-26 | 2009-05-16 | Amira Pharmaceuticals Inc | 5-lipoxygenase activating protein (flap) inhibitor |
| EP2234608A2 (en) | 2007-12-11 | 2010-10-06 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitors using metal binding moieties in combination with targeting moieties |
| SI2250161T1 (sl) | 2008-01-18 | 2014-04-30 | Atopix Therapeutics Limited | Spojine, ki imajo aktivnost crth2 antagonista |
| US7750027B2 (en) | 2008-01-18 | 2010-07-06 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
| JP2011509991A (ja) * | 2008-01-22 | 2011-03-31 | オキサジェン リミテッド | Ｃｒｔｈ２アンタゴニスト活性を有する化合物 |
| JP2011509990A (ja) * | 2008-01-22 | 2011-03-31 | オキサジェン リミテッド | Ｃｒｔｈ２アンタゴニスト活性を有する化合物 |
| JP5791500B2 (ja) * | 2008-05-23 | 2015-10-07 | パンミラ ファーマシューティカルズ，エルエルシー． | ５−リポキシゲナーゼ活性化タンパク質阻害剤 |
| US8546431B2 (en) | 2008-10-01 | 2013-10-01 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| CA2877474A1 (en) * | 2011-06-20 | 2012-12-27 | Myrexis, Inc. | Compounds and therapeutic uses thereof |
| GB201322273D0 (en) | 2013-12-17 | 2014-01-29 | Atopix Therapeutics Ltd | Process |
| GB201407807D0 (en) | 2014-05-02 | 2014-06-18 | Atopix Therapeutics Ltd | Polymorphic form |
| GB201407820D0 (en) | 2014-05-02 | 2014-06-18 | Atopix Therapeutics Ltd | Polymorphic form |
| WO2019191410A1 (en) * | 2018-03-29 | 2019-10-03 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Inhibitors for the β-catenin / t-cell factor protein–protein interaction |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL125443C (enExample) * | 1963-06-06 | |||
| US3370063A (en) * | 1964-10-05 | 1968-02-20 | Mcneilab Inc | Substituted dimethoxy indoles and method of making the same |
| US3621027A (en) * | 1968-03-18 | 1971-11-16 | Endo Lab | 1-aminoalkyl-2,6-diaryl 4,5,6,7 tetrahydro-4-oxindales |
| US3931229A (en) * | 1973-08-23 | 1976-01-06 | Warner-Lambert Company | 3-Thiomethyl-2[2-(dialkylamino)ethyl]indoles |
| US4059583A (en) * | 1975-11-13 | 1977-11-22 | Mcneil Laboratories, Incorporated | Substituted indoles |
| AU523536B2 (en) * | 1977-08-26 | 1982-08-05 | Wellcome Foundation Limited, The | Imidazoles and methods of preparing them |
| US4140858A (en) * | 1977-12-19 | 1979-02-20 | Warner-Lambert Company | 3-(1H-imidazol-1-ylmethyl)-2-(disubstitutedaminomethyl)indoles and a method for their production |
| EP0003901B1 (en) * | 1978-02-24 | 1981-08-05 | Pfizer Limited | 3-(imidazol-1-ylalkyl)indoles as selective inhibitors of thromboxane synthetase,pharmaceutical compositions thereof, and methods for preparing them |
-
1980
- 1980-01-31 DK DK042580A patent/DK151884C/da active
- 1980-03-04 CS CS801492A patent/CS253702B2/cs unknown
- 1980-03-04 HU HU80498A patent/HU184727B/hu not_active IP Right Cessation
- 1980-03-05 US US06/127,298 patent/US4273782A/en not_active Expired - Lifetime
- 1980-03-05 SE SE8001736A patent/SE440778B/sv not_active IP Right Cessation
- 1980-03-05 PL PL1980222470A patent/PL128296B1/pl unknown
- 1980-03-05 GR GR61368A patent/GR67237B/el unknown
- 1980-03-05 LU LU82224A patent/LU82224A1/fr unknown
- 1980-03-05 YU YU614/80A patent/YU41911B/xx unknown
- 1980-03-05 ES ES489220A patent/ES489220A0/es active Granted
- 1980-03-05 IL IL59524A patent/IL59524A/xx unknown
- 1980-03-05 FI FI800672A patent/FI66860C/fi not_active IP Right Cessation
- 1980-03-05 SU SU802891745A patent/SU1277894A3/ru active
- 1980-03-05 PH PH23726A patent/PH15198A/en unknown
- 1980-03-05 NZ NZ193052A patent/NZ193052A/en unknown
- 1980-03-06 BE BE0/199699A patent/BE882113A/fr not_active IP Right Cessation
- 1980-03-06 NL NLAANVRAGE8001351,A patent/NL182959C/xx not_active IP Right Cessation
- 1980-03-06 KR KR1019800000931A patent/KR850000760B1/ko not_active Expired
- 1980-03-06 NO NO800650A patent/NO152217C/no unknown
- 1980-03-06 DD DD80219495A patent/DD149525A5/de not_active IP Right Cessation
- 1980-03-06 JP JP2856380A patent/JPS55133380A/ja active Granted
- 1980-03-06 AR AR280198A patent/AR227015A1/es active
- 1980-03-06 CH CH1781/80A patent/CH649546A5/de not_active IP Right Cessation
- 1980-03-06 IT IT20399/80A patent/IT1218420B/it active
- 1980-03-06 FR FR8005054A patent/FR2450832A1/fr active Granted
- 1980-03-06 AU AU56231/80A patent/AU516957B2/en not_active Ceased
- 1980-03-06 DE DE19803008632 patent/DE3008632A1/de active Granted
- 1980-03-06 AT AT0125780A patent/AT375366B/de not_active IP Right Cessation
- 1980-03-06 IE IE453/80A patent/IE49542B1/en not_active IP Right Cessation
- 1980-03-06 ZA ZA00801328A patent/ZA801328B/xx unknown
- 1980-03-06 CA CA000347143A patent/CA1120479A/en not_active Expired
- 1980-03-06 PT PT70914A patent/PT70914A/pt not_active IP Right Cessation
- 1980-11-14 ES ES496889A patent/ES496889A0/es active Granted
-
1984
- 1984-09-21 SG SG67284A patent/SG67284G/en unknown
- 1984-10-05 KE KE3467A patent/KE3467A/xx unknown
- 1984-11-15 HK HK898/84A patent/HK89884A/xx unknown
-
1985
- 1985-12-30 MY MY285/85A patent/MY8500285A/xx unknown
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