IL94258A - Heterocyclic n-oxide derivatives of substituted benzo (5,6)-cyclohepta-pyridines, process for their preparation, compositions and methods of use - Google Patents
Heterocyclic n-oxide derivatives of substituted benzo (5,6)-cyclohepta-pyridines, process for their preparation, compositions and methods of useInfo
- Publication number
- IL94258A IL94258A IL9425890A IL9425890A IL94258A IL 94258 A IL94258 A IL 94258A IL 9425890 A IL9425890 A IL 9425890A IL 9425890 A IL9425890 A IL 9425890A IL 94258 A IL94258 A IL 94258A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- alkyl
- formula
- halo
- double bond
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims description 12
- 230000008569 process Effects 0.000 title claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 title claims description 5
- OZVMEJXYSDZMDV-UHFFFAOYSA-N 11h-benzo[1,2]cyclohepta[3,4-b]pyridine Chemical class C1=CC2=NC=CC=C2CC2=CC=CC=C21 OZVMEJXYSDZMDV-UHFFFAOYSA-N 0.000 title abstract description 4
- 239000000203 mixture Substances 0.000 title description 82
- 150000001875 compounds Chemical class 0.000 claims abstract description 215
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 239000012453 solvate Substances 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 5
- 206010020751 Hypersensitivity Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 125000000815 N-oxide group Chemical group 0.000 claims description 4
- 230000007815 allergy Effects 0.000 claims description 4
- 239000007822 coupling agent Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 1
- -1 Heterocyclic N-oxide Chemical class 0.000 abstract description 26
- 230000003266 anti-allergic effect Effects 0.000 abstract description 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 83
- 239000000243 solution Substances 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 29
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 27
- 108010003541 Platelet Activating Factor Proteins 0.000 description 27
- 239000012267 brine Substances 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 239000007787 solid Substances 0.000 description 27
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000012300 argon atmosphere Substances 0.000 description 17
- 239000012141 concentrate Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 14
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 239000011521 glass Substances 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 11
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- 229910021529 ammonia Inorganic materials 0.000 description 9
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 210000004623 platelet-rich plasma Anatomy 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 230000002776 aggregation Effects 0.000 description 7
- 238000004220 aggregation Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 239000012038 nucleophile Substances 0.000 description 7
- 238000010791 quenching Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
- 239000007832 Na2SO4 Substances 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 230000001387 anti-histamine Effects 0.000 description 6
- 239000000739 antihistaminic agent Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 6
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 150000001204 N-oxides Chemical class 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 230000003042 antagnostic effect Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- HWWYDZCSSYKIAD-UHFFFAOYSA-N 3,5-dimethylpyridine Chemical compound CC1=CN=CC(C)=C1 HWWYDZCSSYKIAD-UHFFFAOYSA-N 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 150000004795 grignard reagents Chemical class 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- XYBOIZQGIVYRFV-UHFFFAOYSA-N n-tert-butyl-3-methylpyridine-2-carboxamide Chemical compound CC1=CC=CN=C1C(=O)NC(C)(C)C XYBOIZQGIVYRFV-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
- DDGRAFHHXYIQQR-UHFFFAOYSA-N 1-chloro-3-(chloromethyl)benzene Chemical compound ClCC1=CC=CC(Cl)=C1 DDGRAFHHXYIQQR-UHFFFAOYSA-N 0.000 description 3
- MYGXGCCFTPKWIH-UHFFFAOYSA-N 4-chloro-1-methylpiperidine Chemical compound CN1CCC(Cl)CC1 MYGXGCCFTPKWIH-UHFFFAOYSA-N 0.000 description 3
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 3
- 206010006482 Bronchospasm Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 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 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 229940125715 antihistaminic agent Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
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- 238000004821 distillation Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 229960001340 histamine Drugs 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- 239000003848 thrombocyte activating factor antagonist Substances 0.000 description 3
- RNYCGIOXRWNPLF-UHFFFAOYSA-N 1,2,6-trimethylpiperidin-4-ol Chemical compound CC1CC(O)CC(C)N1C RNYCGIOXRWNPLF-UHFFFAOYSA-N 0.000 description 2
- IZXWCDITFDNEBY-UHFFFAOYSA-N 1-(chloromethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCl)C=C1 IZXWCDITFDNEBY-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- MYBGPKXHLYUSQF-UHFFFAOYSA-N 3,5-dimethylpyridine-2-carbonitrile Chemical compound CC1=CN=C(C#N)C(C)=C1 MYBGPKXHLYUSQF-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- BBFQZTWMDAJXDZ-UHFFFAOYSA-N 4-azatricyclo[9.4.0.03,8]pentadeca-1(15),3(8),6,9,11,13-hexaen-2-one Chemical compound N1C2=C(C=CC1)C=CC1=C(C2=O)C=CC=C1 BBFQZTWMDAJXDZ-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- WMQNOYVVLMIZDV-UHFFFAOYSA-N 8-chloro-5,6-dihydrobenzo[1,2]cyclohepta[2,4-b]pyridin-11-one Chemical compound C1CC2=CC=CN=C2C(=O)C2=CC=C(Cl)C=C12 WMQNOYVVLMIZDV-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- 208000009079 Bronchial Spasm Diseases 0.000 description 2
- 208000014181 Bronchial disease Diseases 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QCWTWMJMLSKQCJ-UHFFFAOYSA-N Isonicotinic acid N-oxide Chemical compound OC(=O)C1=CC=[N+]([O-])C=C1 QCWTWMJMLSKQCJ-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- VDAPAPMSRXFUDA-UHFFFAOYSA-N [4-(8-chloro-5,6-dihydrobenzo[1,2]cyclohepta[2,4-b]pyridin-11-ylidene)piperidin-1-yl]-pyridin-3-ylmethanone Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C(CC1)CCN1C(=O)C1=CC=CN=C1 VDAPAPMSRXFUDA-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
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- ABIVRLRIGJRUGF-UHFFFAOYSA-N cyclohepta[b]pyridin-5-one Chemical compound O=C1C=CC=CC2=NC=CC=C12 ABIVRLRIGJRUGF-UHFFFAOYSA-N 0.000 description 1
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- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
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- 238000004817 gas chromatography Methods 0.000 description 1
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- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
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- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
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- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
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- 230000001404 mediated effect Effects 0.000 description 1
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 1
- 229960002329 methacholine Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- WLAUSNCXMJIKJF-UHFFFAOYSA-N n-tert-butyl-3,5-dimethylpyridine-2-carboxamide Chemical compound CC1=CN=C(C(=O)NC(C)(C)C)C(C)=C1 WLAUSNCXMJIKJF-UHFFFAOYSA-N 0.000 description 1
- DYZFUWRIGTVCKS-UHFFFAOYSA-N n-tert-butyl-3-[2-(3-chlorophenyl)ethyl]pyridine-2-carboxamide Chemical compound CC(C)(C)NC(=O)C1=NC=CC=C1CCC1=CC=CC(Cl)=C1 DYZFUWRIGTVCKS-UHFFFAOYSA-N 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000003378 silver Chemical class 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000006478 transmetalation reaction Methods 0.000 description 1
- SWGJCIMEBVHMTA-UHFFFAOYSA-K trisodium;6-oxido-4-sulfo-5-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=C(S([O-])(=O)=O)C2=C1 SWGJCIMEBVHMTA-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Cosmetics (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/345,604 US5089496A (en) | 1986-10-31 | 1989-05-01 | Benzo[5,6]cycloheptapyridine compounds, compositions and method of treating allergies |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL94258A0 IL94258A0 (en) | 1991-03-10 |
| IL94258A true IL94258A (en) | 1994-10-07 |
Family
ID=23355693
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9425890A IL94258A (en) | 1989-05-01 | 1990-05-02 | Heterocyclic n-oxide derivatives of substituted benzo (5,6)-cyclohepta-pyridines, process for their preparation, compositions and methods of use |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US5089496A (de) |
| EP (2) | EP0471750A1 (de) |
| JP (1) | JP2863629B2 (de) |
| KR (1) | KR950009859B1 (de) |
| AT (1) | ATE114650T1 (de) |
| AU (1) | AU643946B2 (de) |
| CA (1) | CA2053903C (de) |
| CZ (1) | CZ414491A3 (de) |
| DE (1) | DE69014393T2 (de) |
| DK (1) | DK0396083T3 (de) |
| ES (1) | ES2064520T3 (de) |
| FI (1) | FI102609B (de) |
| IE (1) | IE66392B1 (de) |
| IL (1) | IL94258A (de) |
| NO (1) | NO179674C (de) |
| NZ (1) | NZ233495A (de) |
| OA (1) | OA09521A (de) |
| WO (1) | WO1990013548A1 (de) |
| ZA (1) | ZA903303B (de) |
Families Citing this family (107)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5438062A (en) * | 1986-10-31 | 1995-08-01 | Schering Corporation | Benzo(5,6)cycloheptapyridines, compositions and methods of use |
| US5665726A (en) * | 1986-10-31 | 1997-09-09 | Schering Corporation | Benzo[5,6]cycloheptapyridines, compositions and methods of use |
| EP0489726B1 (de) * | 1989-09-01 | 1994-03-30 | Total Raffinage Distribution S.A. | Verfahren und einrichtung zum dampfkracken von kohlenwasserstoffen in der wirbelschichtphase |
| NZ238629A (en) * | 1990-06-22 | 1993-09-27 | Schering Corp | Bis-benzo- or benzopyrido-cyclohepta (where z is c, o, s or n) piperidine, piperidylidene or piperazine compounds, medicaments and methods of preparation |
| DE69109871T2 (de) * | 1990-10-10 | 1995-09-14 | Schering Corp., Kenilworth, N.J. | Pyridin- und pyridin-n-oxid-derivate von diarylmethyl- piperidinen oder piperazinen, deren zusammensetzungen und anwendung. |
| US5416087A (en) * | 1990-10-10 | 1995-05-16 | Wong; Jesse K. | Bis-benzo, cyclohepta piperidylidene, piperidine and piperazine compounds, compositions and methods of use |
| DE69110685T2 (de) * | 1990-10-10 | 1995-11-09 | Schering Corp | Substituierte imidazobenzazepine und imidazopyridoazepine. |
| AU2028892A (en) * | 1991-05-23 | 1992-12-30 | Schering Corporation | Novel benzopyrido piperidylidene compounds, compositions, methods of manufacture and methods of use |
| JPH06509341A (ja) * | 1991-07-23 | 1994-10-20 | シェリング・コーポレーション | 新規ベンゾピリドピペリジリデン化合物、組成物、製造方法および使用方法 |
| JPH07505394A (ja) * | 1992-03-27 | 1995-06-15 | シェリング・コーポレーション | 橋渡しビスアリールカルビノール誘導体,組成物および使用法 |
| JPH07505393A (ja) * | 1992-03-27 | 1995-06-15 | シェリング・コーポレーション | 非橋渡しビスアリールカルビノール誘導体,組成物および使用法 |
| WO1993023400A1 (en) * | 1992-05-19 | 1993-11-25 | Schering Corporation | Pentacyclic antihistamines |
| ES2042421B1 (es) * | 1992-05-22 | 1994-08-01 | Uriach & Cia Sa J | Procedimiento para la obtencion de la 8-cloro-11-*1-*(5-metil-3-piridil)metil*-4-piperidiliden*-6,11-dihidro-5h-benzo*5,6*ciclohepta*1,2-b*piridina. |
| US5661152A (en) * | 1993-10-15 | 1997-08-26 | Schering Corporation | Tricyclic sulfonamide compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| US5719148A (en) * | 1993-10-15 | 1998-02-17 | Schering Corporation | Tricyclic amide and urea compounds useful for inhibition of g-protein function and for treatment of proliferative diseases |
| US6075025A (en) | 1993-10-15 | 2000-06-13 | Schering Corporation | Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| IL111235A (en) * | 1993-10-15 | 2001-03-19 | Schering Plough Corp | Medicinal preparations for inhibiting protein G activity and for the treatment of malignant diseases, containing tricyclic compounds, some such new compounds and a process for the preparation of some of them |
| US5721236A (en) * | 1993-10-15 | 1998-02-24 | Schering Corporation | Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| US6365588B1 (en) | 1993-10-15 | 2002-04-02 | Schering Corporation | Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| ES2087818B1 (es) * | 1993-11-24 | 1997-03-16 | Uriach & Cia Sa J | 8-cloro-11-(1-((5-metil-3-piridil)metil)-4-piperidiliden)-6,11-dihidro-5h-benzo-(5,6)cicloheptal(1,2-b)piridina, fumarato. |
| US5538986A (en) * | 1993-12-06 | 1996-07-23 | Schering Corporation | Tricyclic derivatives, compositions and methods of use |
| US5464840A (en) * | 1993-12-06 | 1995-11-07 | Schering Corporation | Tricyclic derivatives, compositions and methods of use |
| US5574173A (en) * | 1993-12-06 | 1996-11-12 | Schering Corporation | Tricyclic derivatives, compositions and methods of use |
| US6524832B1 (en) | 1994-02-04 | 2003-02-25 | Arch Development Corporation | DNA damaging agents in combination with tyrosine kinase inhibitors |
| ES2080699B1 (es) * | 1994-07-27 | 1996-10-16 | Farmahispania S A | Nuevos derivados de 2-(1-etoxicarbonil-4-piperidiliden)metil)piridina y un procedimiento para su obtencion. |
| ES2080700B1 (es) * | 1994-07-27 | 1996-10-16 | Farmihispania S A | Nuevo procedimiento para la obtencion de loratadina. |
| ES2087026B1 (es) * | 1994-07-28 | 1997-03-16 | Uriach & Cia Sa J | Nuevo derivado de la benzo(5,6)ciclohepta- (1.2-b) piridina. |
| US5595997A (en) * | 1994-12-30 | 1997-01-21 | Sepracor Inc. | Methods and compositions for treating allergic rhinitis and other disorders using descarboethoxyloratadine |
| US7211582B1 (en) | 1994-12-30 | 2007-05-01 | Sepracor Inc. | Methods for treating urticaria using descarboethoxyloratadine |
| US7214683B1 (en) | 1994-12-30 | 2007-05-08 | Sepracor Inc. | Compositions of descarboethoxyloratadine |
| US5700806A (en) * | 1995-03-24 | 1997-12-23 | Schering Corporation | Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| US5684013A (en) * | 1995-03-24 | 1997-11-04 | Schering Corporation | Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases |
| IL117798A (en) * | 1995-04-07 | 2001-11-25 | Schering Plough Corp | Tricyclic compounds useful for inhibiting the function of protein - G and for the treatment of malignant diseases, and pharmaceutical preparations containing them |
| US5801175A (en) | 1995-04-07 | 1998-09-01 | Schering Corporation | Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| US5891872A (en) * | 1995-04-07 | 1999-04-06 | Schering Corporation | Tricyclic compounds |
| US5712280A (en) * | 1995-04-07 | 1998-01-27 | Schering Corporation | Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| JP3779349B2 (ja) * | 1995-04-24 | 2006-05-24 | 興和株式会社 | ピペリジン誘導体 |
| TW350844B (en) * | 1995-12-22 | 1999-01-21 | Schering Corp | Tricyclic amides useful to inhibition of G-protein function and for treatment of proliferative diseases |
| AU769687B2 (en) * | 1995-12-22 | 2004-01-29 | Merck Sharp & Dohme Corp. | Tricyclic amides useful for inhibition of G-protein function and for treatment of proliferative diseases |
| US5874442A (en) * | 1995-12-22 | 1999-02-23 | Schering-Plough Corporation | Tricyclic amides useful for inhibition of G-protein function and for treatment of proliferative disease |
| US6323206B1 (en) | 1996-07-12 | 2001-11-27 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US5925757A (en) * | 1996-07-26 | 1999-07-20 | Schering Corporation | Method for preparing carboxamides |
| US5861395A (en) * | 1996-09-13 | 1999-01-19 | Schering Corporation | Compounds useful for inhibition of farnesyl proteins transferase |
| US5965570A (en) * | 1996-09-13 | 1999-10-12 | Schering Corporation | Tricyclic piperidinyl compounds useful as inhibitors of farnesyl-protein transferase |
| US5994364A (en) | 1996-09-13 | 1999-11-30 | Schering Corporation | Tricyclic antitumor farnesyl protein transferase inhibitors |
| ATE282036T1 (de) * | 1996-09-13 | 2004-11-15 | Schering Corp | Trizyklische antitumor verbindungen mit farnesyl protein transferase inhibierender wirkung |
| NZ334341A (en) * | 1996-09-13 | 2001-01-26 | Schering Corp | Substituted benzocycloheptapyridine useful as inhibitors of farnesyl-protein transferase |
| BR9712831A (pt) * | 1996-09-13 | 1999-11-16 | Schering Corp | Inibidores tricìclicos de farnesil proteìna transferase |
| US6030982A (en) | 1996-09-13 | 2000-02-29 | Schering Corporationm | Compounds useful for inhibition of farnesyl protein transferase |
| BR9712980A (pt) * | 1996-09-13 | 2000-04-18 | Schering Corp | Compostos úteis para inibição de transferase de proteina de farnesila |
| US5945429A (en) * | 1996-09-13 | 1999-08-31 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US5985879A (en) * | 1996-09-13 | 1999-11-16 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US5958890A (en) * | 1996-09-13 | 1999-09-28 | Schering Corporation | Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| US6071907A (en) * | 1996-09-13 | 2000-06-06 | Schering Corporation | Tricyclic compounds useful as FPT inhibitors |
| BR9712826A (pt) * | 1996-09-13 | 1999-11-16 | Schering Corp | Novos compostos de piperidinila tricìclica úteis como inibidores de transferase de proteìna farnesil |
| AU7243298A (en) * | 1996-09-13 | 1998-08-03 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US6040305A (en) * | 1996-09-13 | 2000-03-21 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US6130229A (en) * | 1996-10-09 | 2000-10-10 | Schering Corporation | Tricyclic compounds having activity as RAS-FPT inhibitors |
| US5900421A (en) * | 1997-02-11 | 1999-05-04 | Sepracor Inc. | Methods and compositions for treating allergic asthma and dermatitis using descarboethoxyloratadine |
| CH688412A5 (de) * | 1997-03-11 | 1997-09-15 | Cilag Ag | Verfahren zur Herstellung von 1,4-disubstituierten Piperidinverbindungen. |
| EP0977739B1 (de) * | 1997-03-25 | 2003-10-29 | Schering Corporation | Synthese von zwischenprodukten anwendbar in der herstellung von tricyclischen verbindungen |
| US5998620A (en) * | 1997-03-25 | 1999-12-07 | Schering Corporation | Synthesis of intermediates useful in preparing tricyclic compounds |
| GB2323783A (en) * | 1997-04-02 | 1998-10-07 | Ferring Bv Group Holdings | Inhibitors of farnesyl protein transferase |
| US5760232A (en) * | 1997-06-16 | 1998-06-02 | Schering Corporation | Synthesis of intermediates useful in preparing bromo-substituted tricyclic compounds |
| KR20010013828A (ko) * | 1997-06-17 | 2001-02-26 | 둘락 노먼 씨. | 파르네실 단백질 트랜스퍼라제의 억제에 유용한벤조(5,6)사이클로헵타(1,2b)피리딘 유도체 |
| US6051582A (en) * | 1997-06-17 | 2000-04-18 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US6218401B1 (en) | 1997-06-17 | 2001-04-17 | Schering Corporation | Phenyl-substituted tricyclic inhibitors of farnesyl-protein transferase |
| US6576639B1 (en) | 1997-06-17 | 2003-06-10 | Schering Corporation | Compounds for the inhibition of farnesyl protein transferase |
| US6689789B2 (en) | 1997-06-17 | 2004-02-10 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US5925639A (en) * | 1997-06-17 | 1999-07-20 | Schering Corporation | Keto amide derivatives useful as farnesyl protein transferase inhibitors |
| EP0988300B1 (de) * | 1997-06-17 | 2002-08-28 | Schering Corporation | Benzo[5,6]cyclohepta[1,2-b]pyridine derivate als farnesyl protein transferase inhibitoren |
| US6228865B1 (en) | 1997-06-17 | 2001-05-08 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US5939416A (en) * | 1997-06-17 | 1999-08-17 | Schering Corporation | Benzo (5,6) cycloheptapyridine compounds useful as farnesyl protein transferase inhibitors |
| US5877177A (en) * | 1997-06-17 | 1999-03-02 | Schering Corporation | Carboxy piperidylacetamide tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| US6211193B1 (en) | 1997-06-17 | 2001-04-03 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US5852034A (en) * | 1997-06-17 | 1998-12-22 | Schering Corporation | Benzo(5,6)cycloheptapyridine cyclic ureas and lactams useful as farnesyl protein transferase inhibitors |
| US6225322B1 (en) * | 1997-06-17 | 2001-05-01 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US6239140B1 (en) | 1997-06-17 | 2001-05-29 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US6159984A (en) * | 1997-06-17 | 2000-12-12 | Schering Corporation | Farnesyl protein transferase inhibitors |
| US5925648A (en) * | 1997-07-29 | 1999-07-20 | Schering Corporation | Tricyclic N-cyanoimines useful as inhibitors of a farnesyl-protein transferase |
| US5958940A (en) * | 1997-09-11 | 1999-09-28 | Schering Corporation | Tricyclic compounds useful as inhibitors of farnesyl-protein transferase |
| CA2305801A1 (en) * | 1997-10-10 | 1999-04-22 | Schering Corporation | Ethyl 4-(8-chloro-5, 6-dihydro-11h- benzo[5,6]cyclohepta [1,2-b]pyridin -11-ylidene)-1- piperidene carboxylate polymorph |
| US6632455B2 (en) | 1997-12-22 | 2003-10-14 | Schering Corporation | Molecular dispersion composition with enhanced bioavailability |
| US6433165B1 (en) | 1998-01-21 | 2002-08-13 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6509346B2 (en) | 1998-01-21 | 2003-01-21 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6613905B1 (en) | 1998-01-21 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| WO1999037651A1 (en) | 1998-01-21 | 1999-07-29 | Millenium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| DE69919720D1 (de) * | 1998-07-24 | 2004-09-30 | Russinsky Ltd | Verfahren zur herstellung von benzocycloheptapyridin-11-one |
| US7271176B2 (en) * | 1998-09-04 | 2007-09-18 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use thereof |
| AR028138A1 (es) | 1998-11-20 | 2003-04-30 | Schering Corp | Sintesis de intermediarios utiles para preparar compuestos triciclicos |
| US6372909B1 (en) | 1998-11-20 | 2002-04-16 | Schering Corporation | Synthesis of intermediates useful in preparing tricyclic compounds |
| US6316462B1 (en) | 1999-04-09 | 2001-11-13 | Schering Corporation | Methods of inducing cancer cell death and tumor regression |
| US6455554B1 (en) | 1999-06-07 | 2002-09-24 | Targacept, Inc. | Oxopyridinyl pharmaceutical compositions and methods for use |
| US6100274A (en) * | 1999-07-07 | 2000-08-08 | Schering Corporation | 8-chloro-6,11-dihydro-11- ](4-piperidylidine)-5H-benzo[5,6]cyclohepta[1,2-bpyridine oral compositions |
| WO2001009137A1 (en) * | 1999-07-28 | 2001-02-08 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6114346A (en) | 1999-10-22 | 2000-09-05 | Schering Corporation | Treating sleep disorders using desloratadine |
| WO2001045668A2 (en) * | 1999-12-20 | 2001-06-28 | Schering Corporation | Stable extended release oral dosage composition comprising pseudoephedrine and desloratadine |
| WO2001045676A2 (en) | 1999-12-20 | 2001-06-28 | Schering Corporation | Extended release oral dosage composition |
| US7405223B2 (en) | 2000-02-03 | 2008-07-29 | Schering Corporation | Treating allergic and inflammatory conditions |
| AU2001253602A1 (en) | 2000-04-18 | 2001-10-30 | Schering Corporation | Synthesis of intermediates useful in preparing tricyclic compounds |
| AR033680A1 (es) * | 2000-08-30 | 2004-01-07 | Schering Corp | Compuestos triciclicos utiles como inhibidores de la farnesil proteino transferasa y su uso para la manufactura de medicamentos como agentes antitumorales |
| US7342016B2 (en) * | 2000-08-30 | 2008-03-11 | Schering Corporation | Farnesyl protein transferase inhibitors as antitumor agents |
| US6645966B2 (en) | 2001-01-22 | 2003-11-11 | Schering Corporation | Treatment of malaria with farnesyl protein transferase inhibitors |
| US7541365B2 (en) * | 2001-11-21 | 2009-06-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| ATE320431T1 (de) | 2001-11-21 | 2006-04-15 | Millennium Pharm Inc | Chemokine rezeptor antagonisten und methoden zu deren anwendung |
| TWI291467B (en) * | 2002-11-13 | 2007-12-21 | Millennium Pharm Inc | CCR1 antagonists and methods of use therefor |
| CN103113348B (zh) * | 2013-02-18 | 2015-03-25 | 扬子江药业集团江苏海慈生物药业有限公司 | 枸地氯雷他定的假多晶型及其制备方法 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3419565A (en) * | 1963-04-24 | 1968-12-31 | Schering Corp | Aza-dibenzocycloheptenes |
| DE1470314B2 (de) * | 1963-04-24 | 1974-07-11 | Scherico Ltd., Luzern (Schweiz) | 5-Substituierte 4-Azadibenzocyloheptene und Verfahren zu ihrer Herstellung |
| NL132137C (de) * | 1963-04-24 | |||
| US3409621A (en) * | 1966-04-01 | 1968-11-05 | Schering Corp | Piperazino-aza-dibenzo-[a, d]-cycloheptenes |
| CH531000A (de) * | 1970-03-11 | 1972-11-30 | Sandoz Ag | Verfahren zur Herstellung neuer Benzocycloheptathiophene |
| US3717647A (en) * | 1971-04-09 | 1973-02-20 | Schering Corp | Alpha-nicotinoyl phenylacetonitriles |
| US3960894A (en) * | 1972-01-24 | 1976-06-01 | Sandoz Ltd. | 9-Bromo-or chloro-9,10-dihydro-10-dihydro-10-alkoxy-4H-benzo[4,5]cyclo-hepta[1,2-b]thiophen-4-ones |
| US4128549A (en) * | 1976-02-27 | 1978-12-05 | Sandoz Ltd. | Precursors of 4-(1-alkyl-4-piperidylidene-4H-benzo[4,5]cyclohepta-[1,2-b]thiophen-10(9H)-ones |
| US4356184A (en) * | 1980-06-04 | 1982-10-26 | G. D. Searle & Co. | Anti-allergic or antihypertensive 1-piperidinylmethyl benzenamines |
| US4282233B1 (en) * | 1980-06-19 | 2000-09-05 | Schering Corp | Antihistaminic 11-(4-piperidylidene)-5h-benzoÄ5,6Ü-cyclohepta-Ä1,2Ü-pyridines |
| US4355036A (en) * | 1980-06-19 | 1982-10-19 | Schering Corporation | Tricyclic-substituted piperidine antihistamines |
| EP0047226B1 (de) * | 1980-09-02 | 1985-05-15 | Sandoz Ag | Piperidyliden-Derivate, deren Herstellung und diese enthaltende pharmazeutische Zusammensetzungen |
| HU194864B (en) * | 1984-02-15 | 1988-03-28 | Schering Corp | Process for production of 8-chlor-6,11-dihydro-11-(4-piperidilidene)-5h-benzo (5,6)-cyclo-hepta (1,2-b) pyridine and its salts |
| US4616023A (en) * | 1984-04-05 | 1986-10-07 | Merck & Co., Inc. | Pharmaceutical compositions of 4-(dibenzo-[a,d]cycloalkenyl)piperazine compounds and methods |
| US4826853A (en) * | 1986-10-31 | 1989-05-02 | Schering Corporation | 6,11-Dihydro-11-(N-substituted-4-piperidylidene)-5H-benzo(5,6)cyclohepta(1,2-B)pyridines and compositions and methods of use |
| GB8717430D0 (en) * | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
| CA1341044C (en) * | 1988-04-28 | 2000-07-04 | Frank J. Villani | Benzopyrido piperidine, piperidylidene and peperazine compounds, compositions, methods of manufacture and methods of use |
-
1989
- 1989-05-01 US US07/345,604 patent/US5089496A/en not_active Expired - Lifetime
-
1990
- 1990-04-30 ZA ZA903303A patent/ZA903303B/xx unknown
- 1990-04-30 DK DK90108225.5T patent/DK0396083T3/da active
- 1990-04-30 ES ES90108225T patent/ES2064520T3/es not_active Expired - Lifetime
- 1990-04-30 CA CA002053903A patent/CA2053903C/en not_active Expired - Fee Related
- 1990-04-30 IE IE156390A patent/IE66392B1/en not_active IP Right Cessation
- 1990-04-30 EP EP90907629A patent/EP0471750A1/de active Pending
- 1990-04-30 AT AT90108225T patent/ATE114650T1/de not_active IP Right Cessation
- 1990-04-30 AU AU56420/90A patent/AU643946B2/en not_active Ceased
- 1990-04-30 JP JP2507516A patent/JP2863629B2/ja not_active Expired - Lifetime
- 1990-04-30 KR KR1019900702706A patent/KR950009859B1/ko not_active Expired - Fee Related
- 1990-04-30 EP EP90108225A patent/EP0396083B1/de not_active Expired - Lifetime
- 1990-04-30 DE DE69014393T patent/DE69014393T2/de not_active Expired - Fee Related
- 1990-04-30 WO PCT/US1990/002251 patent/WO1990013548A1/en not_active Ceased
- 1990-04-30 NZ NZ233495A patent/NZ233495A/xx unknown
- 1990-05-02 IL IL9425890A patent/IL94258A/en not_active IP Right Cessation
- 1990-12-10 US US07625261 patent/US5151423B1/en not_active Expired - Fee Related
-
1991
- 1991-10-31 OA OA60090A patent/OA09521A/en unknown
- 1991-10-31 NO NO914270A patent/NO179674C/no unknown
- 1991-10-31 FI FI915138A patent/FI102609B/fi active
- 1991-12-30 CZ CS914144A patent/CZ414491A3/cs unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NZ233495A (en) | 1992-11-25 |
| ATE114650T1 (de) | 1994-12-15 |
| NO179674B (no) | 1996-08-19 |
| NO914270D0 (no) | 1991-10-31 |
| NO914270L (no) | 1991-12-23 |
| NO179674C (no) | 1996-11-27 |
| FI102609B1 (fi) | 1999-01-15 |
| EP0471750A1 (de) | 1992-02-26 |
| JPH04504724A (ja) | 1992-08-20 |
| CA2053903A1 (en) | 1990-11-02 |
| DE69014393T2 (de) | 1995-06-01 |
| AU5642090A (en) | 1990-11-29 |
| OA09521A (en) | 1992-11-15 |
| IE901563L (en) | 1990-11-01 |
| IL94258A0 (en) | 1991-03-10 |
| EP0396083A1 (de) | 1990-11-07 |
| CA2053903C (en) | 1999-03-30 |
| KR920700209A (ko) | 1992-02-19 |
| KR950009859B1 (ko) | 1995-08-29 |
| FI102609B (fi) | 1999-01-15 |
| IE66392B1 (en) | 1995-12-27 |
| WO1990013548A1 (en) | 1990-11-15 |
| DK0396083T3 (da) | 1995-02-06 |
| AU643946B2 (en) | 1993-12-02 |
| CZ414491A3 (en) | 1993-05-12 |
| ZA903303B (en) | 1991-01-30 |
| JP2863629B2 (ja) | 1999-03-03 |
| FI915138A0 (fi) | 1991-10-31 |
| ES2064520T3 (es) | 1995-02-01 |
| EP0396083B1 (de) | 1994-11-30 |
| US5151423B1 (en) | 1994-08-30 |
| US5089496A (en) | 1992-02-18 |
| DE69014393D1 (de) | 1995-01-12 |
| US5151423A (en) | 1992-09-29 |
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