IL84235A - 6,11- Dihydro-11-) 4-Piperidylidene (-H5- Benzo-] 5,6 [Cyclohepta-] B-1,2 [Pyridines, process for their preparation and pharmaceutical preparations containing them - Google Patents

6,11- Dihydro-11-) 4-Piperidylidene (-H5- Benzo-] 5,6 [Cyclohepta-] B-1,2 [Pyridines, process for their preparation and pharmaceutical preparations containing them

Info

Publication number: IL84235A
Authority: IL; Israel
Prior art keywords: compound; alkyl; benzo; chloro; halo
Prior art date: 1987-04-28

Application number

IL8423587A

Other languages

English (en)

Hebrew (he)

Other versions

IL84235A0 (en

Original Assignee

Schering Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1987-04-28

Filing date

1987-10-21

Publication date

1994-10-21

1987-10-21 Application filed by Schering Corp filed Critical Schering Corp

1988-03-31 Publication of IL84235A0 publication Critical patent/IL84235A0/xx

1994-10-21 Publication of IL84235A publication Critical patent/IL84235A/en

Links

238000000034 method Methods 0.000 title claims description 20
238000002360 preparation method Methods 0.000 title claims description 20
239000008194 pharmaceutical composition Substances 0.000 title claims description 7
VEHMROQZMLRPSA-UHFFFAOYSA-N 11-piperidin-4-ylidene-5,6-dihydrobenzo[1,2]cyclohepta[3,4-b]pyridine Chemical class C1CNCCC1=C1C2=NC=CC=C2CCC2=CC=CC=C21 VEHMROQZMLRPSA-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 142
125000000217 alkyl group Chemical group 0.000 claims description 34
150000003839 salts Chemical class 0.000 claims description 22
-1 -CF-j Chemical group 0.000 claims description 19
125000001424 substituent group Chemical group 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 5
239000012453 solvate Substances 0.000 claims description 5
HCUOEKSZWPGJIM-YBRHCDHNSA-N (e,2e)-2-hydroxyimino-6-methoxy-4-methyl-5-nitrohex-3-enamide Chemical compound COCC([N+]([O-])=O)\C(C)=C\C(=N/O)\C(N)=O HCUOEKSZWPGJIM-YBRHCDHNSA-N 0.000 claims description 4
101001109689 Homo sapiens Nuclear receptor subfamily 4 group A member 3 Proteins 0.000 claims description 4
101000598778 Homo sapiens Protein OSCP1 Proteins 0.000 claims description 4
101001067395 Mus musculus Phospholipid scramblase 1 Proteins 0.000 claims description 4
102100022673 Nuclear receptor subfamily 4 group A member 3 Human genes 0.000 claims description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
210000002700 urine Anatomy 0.000 claims description 4
241000282693 Cercopithecidae Species 0.000 claims description 3
230000003266 anti-allergic effect Effects 0.000 claims description 3
DRTQHJPVMGBUCF-UCVXFZOQSA-N 1-[(2s,3s,4s,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@H]1[C@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UCVXFZOQSA-N 0.000 claims description 2
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 11
125000000524 functional group Chemical group 0.000 claims 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
UEQNVDYYIWHWNX-UHFFFAOYSA-N 8-chloro-11-piperidin-4-ylidene-5,6-dihydrobenzo[1,2]cyclohepta[2,4-b]pyridin-6-ol Chemical compound C12=CC=C(Cl)C=C2C(O)CC2=CC=CN=C2C1=C1CCNCC1 UEQNVDYYIWHWNX-UHFFFAOYSA-N 0.000 claims 1
GUXVBLYIIGICFV-UHFFFAOYSA-N 8-chloro-11-piperidin-4-ylidene-5h-benzo[1,2]cyclohepta[2,4-b]pyridin-6-one Chemical compound C=1C(Cl)=CC=C2C=1C(=O)CC1=CC=CN=C1C2=C1CCNCC1 GUXVBLYIIGICFV-UHFFFAOYSA-N 0.000 claims 1
229930194542 Keto Natural products 0.000 claims 1
230000000911 decarboxylating effect Effects 0.000 claims 1
125000000468 ketone group Chemical group 0.000 claims 1
239000000203 mixture Substances 0.000 description 52
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
239000007787 solid Substances 0.000 description 25
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 23
238000006243 chemical reaction Methods 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
239000012141 concentrate Substances 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000012300 argon atmosphere Substances 0.000 description 16
230000000694 effects Effects 0.000 description 15
239000007788 liquid Substances 0.000 description 15
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
229910052938 sodium sulfate Inorganic materials 0.000 description 14
235000011152 sodium sulphate Nutrition 0.000 description 14
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 13
DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 13
239000002253 acid Substances 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 12
239000012267 brine Substances 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
239000003826 tablet Substances 0.000 description 11
230000001387 anti-histamine Effects 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
150000001721 carbon Chemical group 0.000 description 9
239000000843 powder Substances 0.000 description 9
238000010992 reflux Methods 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
239000002775 capsule Substances 0.000 description 8
229940093499 ethyl acetate Drugs 0.000 description 8
235000019439 ethyl acetate Nutrition 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
239000002904 solvent Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
VZAWCLCJGSBATP-UHFFFAOYSA-N 1-cycloundecyl-1,2-diazacycloundecane Chemical compound C1CCCCCCCCCC1N1NCCCCCCCCC1 VZAWCLCJGSBATP-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000000739 antihistaminic agent Substances 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
125000005843 halogen group Chemical group 0.000 description 6
231100000225 lethality Toxicity 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
239000012043 crude product Substances 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
239000003814 drug Substances 0.000 description 5
239000000839 emulsion Substances 0.000 description 5
239000008187 granular material 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
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
238000010998 test method Methods 0.000 description 5
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 5
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
229940079593 drug Drugs 0.000 description 4
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 4
239000012458 free base Substances 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
239000003921 oil Substances 0.000 description 4
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 4
PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 4
229960001697 physostigmine Drugs 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000010791 quenching Methods 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 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
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
230000008485 antagonism Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
235000013305 food Nutrition 0.000 description 3
238000009472 formulation Methods 0.000 description 3
229960001340 histamine Drugs 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
239000008101 lactose Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000000463 material Substances 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
230000035939 shock Effects 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
239000008215 water for injection Substances 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
PPNCOQHHSGMKGI-UHFFFAOYSA-N 1-cyclononyldiazonane Chemical compound C1CCCCCCCC1N1NCCCCCCC1 PPNCOQHHSGMKGI-UHFFFAOYSA-N 0.000 description 2
NFDXQGNDWIPXQL-UHFFFAOYSA-N 1-cyclooctyldiazocane Chemical compound C1CCCCCCC1N1NCCCCCC1 NFDXQGNDWIPXQL-UHFFFAOYSA-N 0.000 description 2
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 2
MYGXGCCFTPKWIH-UHFFFAOYSA-N 4-chloro-1-methylpiperidine Chemical compound CN1CCC(Cl)CC1 MYGXGCCFTPKWIH-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
241000700198 Cavia Species 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
208000026935 allergic disease Diseases 0.000 description 2
230000007815 allergy Effects 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000000538 analytical sample Substances 0.000 description 2
229940125715 antihistaminic agent Drugs 0.000 description 2
238000003556 assay Methods 0.000 description 2
125000005605 benzo group Chemical group 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
239000003086 colorant Substances 0.000 description 2
239000012973 diazabicyclooctane Substances 0.000 description 2
230000008030 elimination Effects 0.000 description 2
238000003379 elimination reaction Methods 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
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229940075507 glyceryl monostearate Drugs 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
210000003141 lower extremity Anatomy 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
229910000069 nitrogen hydride Inorganic materials 0.000 description 2
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
235000019271 petrolatum Nutrition 0.000 description 2
239000012071 phase Substances 0.000 description 2
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 2
229920000573 polyethylene Polymers 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
230000002265 prevention Effects 0.000 description 2
239000000047 product Substances 0.000 description 2
239000008213 purified water Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000001624 sedative effect Effects 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(I) nitrate Inorganic materials [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
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 description 2
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239000001814 pectin Substances 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
229940096826 phenylmercuric acetate Drugs 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
HZOTZTANVBDFOF-PBCQUBLHSA-N physostigmine salicylate Chemical compound OC(=O)C1=CC=CC=C1O.C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C HZOTZTANVBDFOF-PBCQUBLHSA-N 0.000 description 1
229960002516 physostigmine salicylate Drugs 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
239000004033 plastic Substances 0.000 description 1
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235000011181 potassium carbonates Nutrition 0.000 description 1
239000002243 precursor Substances 0.000 description 1
ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
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235000015424 sodium Nutrition 0.000 description 1
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239000000126 substance Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
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239000000454 talc Substances 0.000 description 1
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DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 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
- C07D401/04—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
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pulmonology (AREA)
Immunology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

IL8423587A 1987-04-28 1987-10-21 6,11- Dihydro-11-) 4-Piperidylidene (-H5- Benzo-] 5,6 [Cyclohepta-] B-1,2 [Pyridines, process for their preparation and pharmaceutical preparations containing them IL84235A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/043,409 US4804666A (en)	1985-08-14	1987-04-28	Antiallergic 6,11-dihydro-11-(4-piperidylidene)-5H-benzo(5,6)cyclohepta(1,2-B)pyridines

Publications (2)

Publication Number	Publication Date
IL84235A0 IL84235A0 (en)	1988-03-31
IL84235A true IL84235A (en)	1994-10-21

Family

ID=21927034

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL8423587A IL84235A (en)	1987-04-28	1987-10-21	6,11- Dihydro-11-) 4-Piperidylidene (-H5- Benzo-] 5,6 [Cyclohepta-] B-1,2 [Pyridines, process for their preparation and pharmaceutical preparations containing them

Country Status (22)

Country	Link
US (1)	US4804666A (xx)
EP (1)	EP0288640B1 (xx)
JP (1)	JPH0780870B2 (xx)
KR (1)	KR960009426B1 (xx)
AR (1)	AR246520A1 (xx)
AT (1)	ATE80394T1 (xx)
AU (1)	AU612339B2 (xx)
CA (1)	CA1332172C (xx)
DE (1)	DE3781679T2 (xx)
DK (1)	DK540789A (xx)
ES (1)	ES2043665T3 (xx)
FI (1)	FI96858C (xx)
GR (1)	GR3006483T3 (xx)
HK (1)	HK135595A (xx)
HU (1)	HU202520B (xx)
IE (1)	IE61740B1 (xx)
IL (1)	IL84235A (xx)
MX (1)	MX9203282A (xx)
NZ (1)	NZ222253A (xx)
PH (1)	PH26157A (xx)
PT (1)	PT85975B (xx)
WO (1)	WO1988008423A1 (xx)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
KR950004004B1 (ko) *	1988-04-28	1995-04-22	쉐링코포레이션	신규한 벤조피리도 피페리딘, 피페리딜리덴 및 피페라진 화합물, 조성물, 제조방법 및 이용방법
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
US5595997A (en) *	1994-12-30	1997-01-21	Sepracor Inc.	Methods and compositions for treating allergic rhinitis and other disorders using descarboethoxyloratadine
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.
AU4387699A (en) *	1998-07-24	2000-02-14	Russinsky Limited	A process for preparing benzocycloheptapyridin-11-ones
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1987
- 1987-04-28 US US07/043,409 patent/US4804666A/en not_active Expired - Lifetime
- 1987-10-21 IL IL8423587A patent/IL84235A/en not_active IP Right Cessation
- 1987-10-21 NZ NZ222253A patent/NZ222253A/xx unknown
- 1987-10-21 AR AR87309067A patent/AR246520A1/es active
- 1987-10-22 PH PH35970A patent/PH26157A/en unknown
- 1987-10-22 AT AT87309349T patent/ATE80394T1/de not_active IP Right Cessation
- 1987-10-22 EP EP87309349A patent/EP0288640B1/en not_active Expired - Lifetime
- 1987-10-22 PT PT85975A patent/PT85975B/pt not_active IP Right Cessation
- 1987-10-22 DE DE8787309349T patent/DE3781679T2/de not_active Expired - Fee Related
- 1987-10-22 HU HU88308A patent/HU202520B/hu not_active IP Right Cessation
- 1987-10-22 CA CA000549987A patent/CA1332172C/en not_active Expired - Fee Related
- 1987-10-22 JP JP63500439A patent/JPH0780870B2/ja not_active Expired - Fee Related
- 1987-10-22 ES ES87309349T patent/ES2043665T3/es not_active Expired - Lifetime
- 1987-10-22 WO PCT/US1987/002689 patent/WO1988008423A1/en active IP Right Grant
- 1987-10-22 IE IE283987A patent/IE61740B1/en not_active IP Right Cessation
- 1987-10-22 AU AU10465/88A patent/AU612339B2/en not_active Ceased
1988
- 1988-12-28 KR KR88701743A patent/KR960009426B1/ko not_active IP Right Cessation
1989
- 1989-10-24 FI FI895034A patent/FI96858C/fi not_active IP Right Cessation
- 1989-10-30 DK DK540789A patent/DK540789A/da not_active Application Discontinuation
1992
- 1992-06-24 MX MX9203282A patent/MX9203282A/es unknown
- 1992-12-09 GR GR920402839T patent/GR3006483T3/el unknown
1995
- 1995-08-24 HK HK135595A patent/HK135595A/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
IE872839L (en)	1988-10-28
MX9203282A (es)	1992-07-01
IL84235A0 (en)	1988-03-31
EP0288640A1 (en)	1988-11-02
DE3781679D1 (de)	1992-10-15
AR246520A1 (es)	1994-08-31
FI96858C (fi)	1996-09-10
PH26157A (en)	1992-03-18
JPH0780870B2 (ja)	1995-08-30
AU612339B2 (en)	1991-07-11
FI96858B (fi)	1996-05-31
KR960009426B1 (en)	1996-07-19
WO1988008423A1 (en)	1988-11-03
AU1046588A (en)	1988-12-02
DE3781679T2 (de)	1993-01-28
KR890700583A (ko)	1989-04-25
CA1332172C (en)	1994-09-27
JPH02503909A (ja)	1990-11-15
HK135595A (en)	1995-09-01
HU202520B (en)	1991-03-28
IE61740B1 (en)	1994-11-30
EP0288640B1 (en)	1992-09-09
US4804666A (en)	1989-02-14
DK540789D0 (da)	1989-10-30
DK540789A (da)	1989-10-30
ES2043665T3 (es)	1994-01-01
ATE80394T1 (de)	1992-09-15
GR3006483T3 (xx)	1993-06-21
PT85975A (en)	1987-11-01
PT85975B (pt)	1992-07-31
FI895034A0 (fi)	1989-10-24
NZ222253A (en)	1990-08-28

Publication	Publication Date	Title
AU646878B2 (en)	1994-03-10	Bis-benzo or benzopyrido cyclo hepta piperidene, piperidylidene and piperazine compounds and compositions
CA2053903C (en)	1999-03-30	Heterocyclic n-oxide derivatives of substituted benzo[5,6]cycloheptapyridines, compositions and methods of use
KR930002489B1 (ko)	1993-04-02	벤조[5, 6]사이클로헵타피리딘 및 이의 제조방법
IL84235A (en)	1994-10-21	6,11- Dihydro-11-) 4-Piperidylidene (-H5- Benzo-] 5,6 [Cyclohepta-] B-1,2 [Pyridines, process for their preparation and pharmaceutical preparations containing them
JPH0678315B2 (ja)	1994-10-05	新規なベンゾピリド‐ピペリジン、ピペリジリデンおよびピペラジン化合物、組成物、製造法および利用法
US5514687A (en)	1996-05-07	Benzopyrido piperidylidene compounds, compositions, methods of manufacture and method of use
NO173062B (no)	1993-07-12	Analogifremgangsmaate for fremstilling av terapeutisk aktive benzo(5,6)cykloheptapyridiner

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Date	Code	Title
1998-03-10	KB	Patent renewed
2002-02-10	KB	Patent renewed
2006-08-01	MM9K	Patent not in force due to non-payment of renewal fees