IE51015B1 - Heterocyclic compounds,processes for their preparation and pharmaceutical compositions containing them - Google Patents
Heterocyclic compounds,processes for their preparation and pharmaceutical compositions containing themInfo
- Publication number
- IE51015B1 IE51015B1 IE485/81A IE48581A IE51015B1 IE 51015 B1 IE51015 B1 IE 51015B1 IE 485/81 A IE485/81 A IE 485/81A IE 48581 A IE48581 A IE 48581A IE 51015 B1 IE51015 B1 IE 51015B1
- Authority
- IE
- Ireland
- Prior art keywords
- compounds
- formula
- acid addition
- dibenzo
- dihydro
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title claims description 19
- 238000002360 preparation method Methods 0.000 title description 11
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- 239000002253 acid Substances 0.000 claims abstract description 38
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 208000006673 asthma Diseases 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 206010052613 Allergic bronchitis Diseases 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 25
- CJKPKVLFYAXEBS-UHFFFAOYSA-N 2,3,6,7-tetrahydrooxazepine Chemical compound C1CC=CCNO1 CJKPKVLFYAXEBS-UHFFFAOYSA-N 0.000 claims description 22
- 150000004985 diamines Chemical class 0.000 claims description 11
- NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical compound S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 claims description 10
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 239000000155 melt Substances 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000005864 Sulphur Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- VZLKQEPNZIWSFF-UHFFFAOYSA-N 1-pyrrolidin-1-ylpiperidine Chemical compound C1CCCN1N1CCCCC1 VZLKQEPNZIWSFF-UHFFFAOYSA-N 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- -1 pyrrolidino, piperidino Chemical group 0.000 abstract description 12
- 125000003342 alkenyl group Chemical group 0.000 abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 239000011593 sulfur Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 61
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 235000002639 sodium chloride Nutrition 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 11
- AJUMGSLQADLWKL-UHFFFAOYSA-N 1h-azepine;hydrochloride Chemical compound Cl.N1C=CC=CC=C1 AJUMGSLQADLWKL-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000012458 free base Substances 0.000 description 9
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical compound O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 229940093499 ethyl acetate Drugs 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 239000003420 antiserotonin agent Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 230000001387 anti-histamine Effects 0.000 description 3
- 239000000739 antihistaminic agent Substances 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
- 239000001530 fumaric acid Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- BXLGMUXUBVXYED-WLHGVMLRSA-N (E)-but-2-enedioic acid thiazepine Chemical compound S1C=CC=CC=N1.OC(=O)\C=C\C(O)=O BXLGMUXUBVXYED-WLHGVMLRSA-N 0.000 description 2
- GNHGSSSQCHAIEL-UHFFFAOYSA-N 1h-azepine;hydrobromide Chemical compound Br.N1C=CC=CC=C1 GNHGSSSQCHAIEL-UHFFFAOYSA-N 0.000 description 2
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 2
- FPKDBVUHIXYLNP-UHFFFAOYSA-N 6,11-dihydro-5h-benzo[c][1]benzazepin-6-ylmethanamine Chemical compound NCC1NC2=CC=CC=C2CC2=CC=CC=C12 FPKDBVUHIXYLNP-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 2
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- 210000001772 blood platelet Anatomy 0.000 description 2
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- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
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- HQRJVJXBBUDZSD-UHFFFAOYSA-N imidazo[1,5-d][1,4]thiazepine Chemical compound C=1N=CN2C=CSC=CC2=1 HQRJVJXBBUDZSD-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
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- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
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- 239000008096 xylene Substances 0.000 description 2
- OCQAXYHNMWVLRH-ROUUACIJSA-N (2s,3s)-2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical compound O=C([C@](O)(C(=O)O)[C@@](O)(C(O)=O)C(=O)C=1C=CC=CC=1)C1=CC=CC=C1 OCQAXYHNMWVLRH-ROUUACIJSA-N 0.000 description 1
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- OHOWXEDRJQSBEY-UHFFFAOYSA-N 16-chloro-2,4-diazatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),3,7,9,11,15,17-heptaen-3-amine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=C(Cl)C=C21 OHOWXEDRJQSBEY-UHFFFAOYSA-N 0.000 description 1
- JJJBUEABWLWKEV-UHFFFAOYSA-N 16-chloro-N-methyl-13-oxa-2,4-diazatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),7,9,11,15,17-hexaen-3-imine Chemical compound O1C2=CC=CC=C2C2CN=C(NC)N2C2=CC=C(Cl)C=C21 JJJBUEABWLWKEV-UHFFFAOYSA-N 0.000 description 1
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 1
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 description 1
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 1
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 1
- IUQYGXGUFNMQGL-WLHGVMLRSA-N 6,11-dihydro-5h-benzo[c][1]benzazepin-6-ylmethylazanium;(e)-4-hydroxy-4-oxobut-2-enoate Chemical compound OC(=O)\C=C\C(O)=O.NCC1NC2=CC=CC=C2CC2=CC=CC=C12 IUQYGXGUFNMQGL-WLHGVMLRSA-N 0.000 description 1
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- 206010070834 Sensitisation Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
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- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910000091 aluminium hydride Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000002804 anti-anaphylactic effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- JWCQGVNTXQPLTE-UHFFFAOYSA-N azepine-3-thione Chemical compound S=c1ccccnc1 JWCQGVNTXQPLTE-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 239000001926 citrus aurantium l. subsp. bergamia wright et arn. oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- NPUACKRELIJTFM-UHFFFAOYSA-N cr gas Chemical compound C1=NC2=CC=CC=C2OC2=CC=CC=C21 NPUACKRELIJTFM-UHFFFAOYSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- PFBUKDPBVNJDEW-UHFFFAOYSA-N dichlorocarbene Chemical group Cl[C]Cl PFBUKDPBVNJDEW-UHFFFAOYSA-N 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 229960004132 diethyl ether Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- VKXSGUIOOQPGAF-UHFFFAOYSA-N epinastine hydrochloride Chemical compound [H+].[Cl-].C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 VKXSGUIOOQPGAF-UHFFFAOYSA-N 0.000 description 1
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- 238000000605 extraction Methods 0.000 description 1
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- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- INHCSSUBVCNVSK-UHFFFAOYSA-L lithium sulfate Inorganic materials [Li+].[Li+].[O-]S([O-])(=O)=O INHCSSUBVCNVSK-UHFFFAOYSA-L 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- SFJGCXYXEFWEBK-UHFFFAOYSA-N oxazepine Chemical compound O1C=CC=CC=N1 SFJGCXYXEFWEBK-UHFFFAOYSA-N 0.000 description 1
- LWXRDBXEIVCNSZ-UHFFFAOYSA-N oxazepine-3-thione Chemical compound S=C1NOC=CC=C1 LWXRDBXEIVCNSZ-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 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
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
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- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- RBTVSNLYYIMMKS-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CC(N)C1 RBTVSNLYYIMMKS-UHFFFAOYSA-N 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 239000003871 white petrolatum 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/20—Dibenz [b, e] azepines; Hydrogenated dibenz [b, e] azepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/02—Seven-membered rings
- C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D267/16—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D267/20—[b, f]-condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D281/16—[b, f]-condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19803008944 DE3008944A1 (de) | 1980-03-08 | 1980-03-08 | Dibenzimidazoazepine, ihre herstellung und verwendung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE810485L IE810485L (en) | 1981-09-08 |
| IE51015B1 true IE51015B1 (en) | 1986-09-03 |
Family
ID=6096617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE485/81A IE51015B1 (en) | 1980-03-08 | 1981-03-06 | Heterocyclic compounds,processes for their preparation and pharmaceutical compositions containing them |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US4313931A (en, 2012) |
| EP (1) | EP0035749B1 (en, 2012) |
| JP (1) | JPS56139484A (en, 2012) |
| AU (1) | AU535359B2 (en, 2012) |
| BG (1) | BG33886A3 (en, 2012) |
| CA (1) | CA1150253A (en, 2012) |
| CS (2) | CS221288B2 (en, 2012) |
| DD (1) | DD156708A5 (en, 2012) |
| DE (2) | DE3008944A1 (en, 2012) |
| DK (1) | DK154299C (en, 2012) |
| ES (1) | ES8301481A1 (en, 2012) |
| FI (1) | FI70898C (en, 2012) |
| GB (1) | GB2071095B (en, 2012) |
| GR (1) | GR74805B (en, 2012) |
| HK (1) | HK63186A (en, 2012) |
| HU (1) | HU180628B (en, 2012) |
| IE (1) | IE51015B1 (en, 2012) |
| IL (1) | IL62309A (en, 2012) |
| MX (1) | MX6869E (en, 2012) |
| NO (1) | NO162073C (en, 2012) |
| NZ (1) | NZ196446A (en, 2012) |
| PH (1) | PH15839A (en, 2012) |
| PL (1) | PL132141B1 (en, 2012) |
| PT (1) | PT72631B (en, 2012) |
| RO (1) | RO81652B (en, 2012) |
| SU (1) | SU1015829A3 (en, 2012) |
| UA (1) | UA8041A1 (en, 2012) |
| YU (1) | YU42557B (en, 2012) |
| ZA (1) | ZA811500B (en, 2012) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3134672A1 (de) * | 1981-09-02 | 1983-03-17 | Boehringer Ingelheim KG, 6507 Ingelheim | Heterocyclische verbindungen, ihre herstellung und verwendung |
| DE4102148A1 (de) * | 1991-01-25 | 1992-07-30 | Boehringer Ingelheim Kg | Verfahren zur herstellung von 3-amino-9,13b-dihydro-1h-dibenz-(c,f)imidazol(1,5-a)azepin-hydrochlorid |
| DE19542281C2 (de) * | 1995-11-14 | 1997-12-04 | Boehringer Ingelheim Kg | Verwendung von Epinastin für die Behandlung der Migräne |
| DE19954516A1 (de) * | 1999-11-12 | 2001-05-17 | Boehringer Ingelheim Int | Epinastin-haltige Lösungen |
| DE19958460A1 (de) * | 1999-12-03 | 2001-06-07 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Epinastine-Hydrochlorid in der hochschmelzenden Kristallmodifikation |
| US7776315B2 (en) * | 2000-10-31 | 2010-08-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and additional active ingredients |
| US20100310477A1 (en) * | 2000-11-28 | 2010-12-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg. | Pharmaceutical compositions based on anticholingerics and additional active ingredients |
| RU2204563C2 (ru) * | 2001-06-22 | 2003-05-20 | Ярославский государственный технический университет | Гетероциклические о-дикарбонитрилы |
| DE10152973A1 (de) * | 2001-10-26 | 2003-05-08 | Boehringer Ingelheim Int | Neue trockene und wässrige Epinastin-Sirup-Formulierung |
| JP4298212B2 (ja) * | 2002-03-29 | 2009-07-15 | 大日本印刷株式会社 | 塩酸エピナスチン高融点型結晶の製造法 |
| MXPA04009753A (es) * | 2002-04-11 | 2005-06-08 | Konica Minolta Chemical Co Ltd | Metodo de produccion de 6-aminometil-6, 11-dihidro-5h-dibenz- [b,]azepina. |
| JP4514017B2 (ja) * | 2003-03-27 | 2010-07-28 | 大日本印刷株式会社 | 塩酸エピナスチンの製造方法 |
| US8758816B2 (en) * | 2004-11-24 | 2014-06-24 | Meda Pharmaceuticals Inc. | Compositions comprising azelastine and methods of use thereof |
| JP5607291B2 (ja) * | 2004-11-24 | 2014-10-15 | メダ ファーマシューティカルズ インコーポレイテッド | アゼラスチンを含む組成物およびその使用方法 |
| US20070020330A1 (en) | 2004-11-24 | 2007-01-25 | Medpointe Healthcare Inc. | Compositions comprising azelastine and methods of use thereof |
| KR20080034916A (ko) * | 2005-07-08 | 2008-04-22 | 센주 세이야꾸 가부시키가이샤 | 에피나스틴을 포함하는 경피 흡수 안과 제제 |
| US7247623B2 (en) * | 2005-08-19 | 2007-07-24 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with non-drying antihistamines |
| KR101386530B1 (ko) | 2006-12-29 | 2014-04-18 | 케이피엑스 라이프사이언스 주식회사 | 순도 및 수율이 향상된3-아미노-9,13ｂ디하이드로-1Ｈ-디벤즈-[ｃ,ｆ]이미다조[1,5-ａ]-아제핀 염산염의 제조방법 |
| WO2009063504A2 (en) * | 2007-09-24 | 2009-05-22 | Usv Limited | Novel crystal modification of epinastine or salts thereof and process for preparation thereof |
| WO2010021681A2 (en) * | 2008-08-18 | 2010-02-25 | Combinatorx (Singapore) Pte. Ltd. | Compositions and methods for treatment of viral diseases |
| JP2010120960A (ja) * | 2010-02-17 | 2010-06-03 | Dainippon Printing Co Ltd | 塩酸エピナスチンの製造方法 |
| JP6006634B2 (ja) * | 2011-12-28 | 2016-10-12 | 東和薬品株式会社 | イソウレア化合物を用いるエピナスチンの製造方法 |
| CN103172638B (zh) * | 2013-03-13 | 2015-09-16 | 北京朗依制药有限公司 | 一种盐酸依匹斯汀的制备方法 |
| CN104098575B (zh) * | 2013-04-15 | 2016-06-01 | 四川科瑞德凯华制药有限公司 | 一种盐酸依匹斯汀晶型及其制备方法和用途 |
| KR102041389B1 (ko) * | 2017-12-12 | 2019-11-27 | (주)프론트바이오 | N-(9,13b-디하이드로-1H-디벤조[c,f]이미다조[1,5-a]아제핀-3-일)-2-하이드록시벤즈아미드 및 2-((9,13b-디하이드로-1H-디벤조[c,f]이미다조[1,5-a]아제핀-3-일) 카바모일)페닐 아세테이트의 화합물, 이의 제조방법 및 이를 포함하는 항염증 및 진통제 조성물 |
| KR102080239B1 (ko) | 2019-08-06 | 2020-02-21 | 한양대학교 에리카산학협력단 | 에피나스틴의 신규 제조방법 |
| CN115974882A (zh) * | 2023-02-08 | 2023-04-18 | 广州艾格生物科技有限公司 | 一种盐酸依匹斯汀杂质的制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE789410A (fr) * | 1971-10-05 | 1973-01-15 | Akzo Nv | Nieuwe imidazolidine derivaten |
| NL7202963A (en, 2012) * | 1972-03-07 | 1973-09-11 | ||
| NL7414038A (nl) * | 1974-10-28 | 1976-05-03 | Akzo Nv | Nieuwe tetracyclische pyrrolidino derivaten. |
-
1980
- 1980-03-08 DE DE19803008944 patent/DE3008944A1/de not_active Withdrawn
-
1981
- 1981-02-23 US US06/236,818 patent/US4313931A/en not_active Expired - Lifetime
- 1981-03-02 PH PH25292A patent/PH15839A/en unknown
- 1981-03-05 EP EP81101564A patent/EP0035749B1/de not_active Expired
- 1981-03-05 NO NO810762A patent/NO162073C/no not_active IP Right Cessation
- 1981-03-05 JP JP3190381A patent/JPS56139484A/ja active Granted
- 1981-03-05 UA UA3252241A patent/UA8041A1/uk unknown
- 1981-03-05 DD DD81228087A patent/DD156708A5/de not_active IP Right Cessation
- 1981-03-05 YU YU568/81A patent/YU42557B/xx unknown
- 1981-03-05 SU SU813252241A patent/SU1015829A3/ru active
- 1981-03-05 DE DE8181101564T patent/DE3163938D1/de not_active Expired
- 1981-03-06 MX MX819335U patent/MX6869E/es unknown
- 1981-03-06 BG BG051119A patent/BG33886A3/xx unknown
- 1981-03-06 ZA ZA00811500A patent/ZA811500B/xx unknown
- 1981-03-06 HU HU8181572A patent/HU180628B/hu unknown
- 1981-03-06 DK DK103581A patent/DK154299C/da not_active IP Right Cessation
- 1981-03-06 NZ NZ196446A patent/NZ196446A/en unknown
- 1981-03-06 ES ES500150A patent/ES8301481A1/es not_active Expired
- 1981-03-06 CA CA000372485A patent/CA1150253A/en not_active Expired
- 1981-03-06 IE IE485/81A patent/IE51015B1/en not_active IP Right Cessation
- 1981-03-06 GB GB8107114A patent/GB2071095B/en not_active Expired
- 1981-03-06 GR GR64337A patent/GR74805B/el unknown
- 1981-03-06 FI FI810712A patent/FI70898C/fi not_active IP Right Cessation
- 1981-03-06 PT PT72631A patent/PT72631B/pt unknown
- 1981-03-06 AU AU68158/81A patent/AU535359B2/en not_active Expired
- 1981-03-06 CS CS811644A patent/CS221288B2/cs unknown
- 1981-03-06 IL IL62309A patent/IL62309A/xx not_active IP Right Cessation
- 1981-03-06 PL PL1981230036A patent/PL132141B1/pl unknown
- 1981-03-07 RO RO103617A patent/RO81652B/ro unknown
-
1986
- 1986-08-28 HK HK631/86A patent/HK63186A/xx not_active IP Right Cessation
-
1991
- 1991-12-27 CS CS914104A patent/CS410491A3/cs unknown
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| Date | Code | Title | Description |
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| MK9A | Patent expired |