FI92065B - Förfarande för framställning av farmaceutiska piperidinderivat - Google Patents
Förfarande för framställning av farmaceutiska piperidinderivat Download PDFInfo
- Publication number
- FI92065B FI92065B FI886057A FI886057A FI92065B FI 92065 B FI92065 B FI 92065B FI 886057 A FI886057 A FI 886057A FI 886057 A FI886057 A FI 886057A FI 92065 B FI92065 B FI 92065B
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- FI
- Finland
- Prior art keywords
- formula
- ethyl
- compound
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- mmol
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- 238000000034 method Methods 0.000 title claims description 20
- 150000003053 piperidines Chemical class 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- -1 2- (4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl) ethyl Chemical group 0.000 claims description 65
- 150000001875 compounds Chemical class 0.000 claims description 58
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 2
- 239000012429 reaction media Substances 0.000 claims 2
- WAEPFBHQEHYGFN-UHFFFAOYSA-N 1-(2-phenylethyl)piperidin-2-one Chemical compound O=C1CCCCN1CCC1=CC=CC=C1 WAEPFBHQEHYGFN-UHFFFAOYSA-N 0.000 claims 1
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000004132 cross linking Methods 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 159000000000 sodium salts Chemical group 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 150000003536 tetrazoles Chemical class 0.000 claims 1
- 239000000243 solution Substances 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000000460 chlorine Substances 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- 239000002253 acid Substances 0.000 description 12
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 229910004298 SiO 2 Inorganic materials 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 230000000202 analgesic effect Effects 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- WLCAJVVSNAVBSM-UHFFFAOYSA-N oxalic acid;piperidine Chemical compound C1CCNCC1.OC(=O)C(O)=O WLCAJVVSNAVBSM-UHFFFAOYSA-N 0.000 description 5
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 150000004985 diamines Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000008227 sterile water for injection Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- JBKBUTIAVRKFCR-UHFFFAOYSA-N 1-benzyl-n-(2-fluorophenyl)-4-(2h-tetrazol-5-yl)piperidin-4-amine Chemical compound FC1=CC=CC=C1NC1(C=2NN=NN=2)CCN(CC=2C=CC=CC=2)CC1 JBKBUTIAVRKFCR-UHFFFAOYSA-N 0.000 description 2
- SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
- YPURWWNSSQJPQR-UHFFFAOYSA-N 2-oxo-2-piperidin-1-yloxyacetic acid Chemical compound OC(=O)C(=O)ON1CCCCC1 YPURWWNSSQJPQR-UHFFFAOYSA-N 0.000 description 2
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- QMHIMXFNBOYPND-UHFFFAOYSA-N 4-methylthiazole Chemical compound CC1=CSC=N1 QMHIMXFNBOYPND-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000003891 oxalate salts Chemical class 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 125000001401 1,2,4-triazol-4-yl group Chemical group N=1N=C([H])N([*])C=1[H] 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- VUCWMAJEUOWLEY-UHFFFAOYSA-N 1-$l^{1}-azanylpiperidine Chemical compound [N]N1CCCCC1 VUCWMAJEUOWLEY-UHFFFAOYSA-N 0.000 description 1
- DHORCQPBZSDOIQ-UHFFFAOYSA-N 1-benzyl-4-(2-fluoroanilino)piperidine-4-carbonitrile Chemical compound FC1=CC=CC=C1NC1(C#N)CCN(CC=2C=CC=CC=2)CC1 DHORCQPBZSDOIQ-UHFFFAOYSA-N 0.000 description 1
- WRFDXBMXHLRNLO-UHFFFAOYSA-N 1-benzyl-n-phenyl-4-(2h-tetrazol-5-yl)piperidin-4-amine Chemical compound C=1C=CC=CC=1CN(CC1)CCC1(C=1NN=NN=1)NC1=CC=CC=C1 WRFDXBMXHLRNLO-UHFFFAOYSA-N 0.000 description 1
- MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 description 1
- 125000004345 1-phenyl-2-propyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- FMOIXKQKOWLYEK-UHFFFAOYSA-N 2-(2-chloroethyl)thiophene Chemical compound ClCCC1=CC=CS1 FMOIXKQKOWLYEK-UHFFFAOYSA-N 0.000 description 1
- KWVPFECTOKLOBL-KTKRTIGZSA-N 2-[(z)-octadec-9-enoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCO KWVPFECTOKLOBL-KTKRTIGZSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 1
- IFRIJXPBIJQSSL-UHFFFAOYSA-N 4-[[[3-(4-fluorophenyl)-3-(furan-2-yl)propyl]amino]methyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1CNCCC(C=1C=CC(F)=CC=1)C1=CC=CO1 IFRIJXPBIJQSSL-UHFFFAOYSA-N 0.000 description 1
- AYYPQRMTCMCFSL-UHFFFAOYSA-N 4-anilino-1-benzylpiperidine-4-carbonitrile Chemical compound C1CC(C#N)(NC=2C=CC=CC=2)CCN1CC1=CC=CC=C1 AYYPQRMTCMCFSL-UHFFFAOYSA-N 0.000 description 1
- 101100256985 Arabidopsis thaliana SIS3 gene Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 240000008415 Lactuca sativa Species 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010038678 Respiratory depression Diseases 0.000 description 1
- CDKIEBFIMCSCBB-CALJPSDSSA-N SIS3 Chemical compound Cl.C1C=2C=C(OC)C(OC)=CC=2CCN1C(=O)\C=C\C(C1=CC=CN=C1N1C)=C1C1=CC=CC=C1 CDKIEBFIMCSCBB-CALJPSDSSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 239000002869 intravenous anesthetic agent Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- VHHVWBQKVQEXHC-UHFFFAOYSA-N n-[1-benzyl-4-(1-methyltetrazol-5-yl)piperidin-4-yl]-n-phenylpropanamide Chemical compound C1CN(CC=2C=CC=CC=2)CCC1(C=1N(N=NN=1)C)N(C(=O)CC)C1=CC=CC=C1 VHHVWBQKVQEXHC-UHFFFAOYSA-N 0.000 description 1
- BBJPCWPTUBXKGB-UHFFFAOYSA-N n-[1-benzyl-4-(2-methyl-1,2,4-triazol-3-yl)piperidin-4-yl]-n-phenylpropanamide Chemical compound C1CN(CC=2C=CC=CC=2)CCC1(C=1N(N=CN=1)C)N(C(=O)CC)C1=CC=CC=C1 BBJPCWPTUBXKGB-UHFFFAOYSA-N 0.000 description 1
- UHGGLJLFYJQXKY-UHFFFAOYSA-N n-[1-benzyl-4-(2h-tetrazol-5-yl)piperidin-1-ium-4-yl]-n-phenylpropanamide;propanoate Chemical compound CCC([O-])=O.C1C[NH+](CC=2C=CC=CC=2)CCC1(C=1NN=NN=1)N(C(=O)CC)C1=CC=CC=C1 UHGGLJLFYJQXKY-UHFFFAOYSA-N 0.000 description 1
- CDKUYHQVLGJJHD-UHFFFAOYSA-N n-[1-benzyl-4-(4-methyl-1,3-thiazol-2-yl)piperidin-4-yl]-n-phenylpropanamide Chemical compound C1CN(CC=2C=CC=CC=2)CCC1(C=1SC=C(C)N=1)N(C(=O)CC)C1=CC=CC=C1 CDKUYHQVLGJJHD-UHFFFAOYSA-N 0.000 description 1
- INBDMSIHZXMADB-UHFFFAOYSA-N n-[4-(4-methyl-1,3-thiazol-2-yl)-1-(2-pyrazol-1-ylethyl)piperidin-4-yl]-n-phenylpropanamide Chemical compound C1CN(CCN2N=CC=C2)CCC1(C=1SC=C(C)N=1)N(C(=O)CC)C1=CC=CC=C1 INBDMSIHZXMADB-UHFFFAOYSA-N 0.000 description 1
- FJXQREDWAGAOAF-UHFFFAOYSA-N n-[4-(5-ethyl-1,3,4-oxadiazol-2-yl)piperidin-4-yl]-n-phenylpropanamide Chemical compound C1CNCCC1(C=1OC(CC)=NN=1)N(C(=O)CC)C1=CC=CC=C1 FJXQREDWAGAOAF-UHFFFAOYSA-N 0.000 description 1
- YDJXNYNKKXZBMP-UHFFFAOYSA-N n-phenethyl-4-piperidinone Chemical compound C1CC(=O)CCN1CCC1=CC=CC=C1 YDJXNYNKKXZBMP-UHFFFAOYSA-N 0.000 description 1
- LKRMTUUCKBQGFO-UHFFFAOYSA-N n-phenylpiperidin-4-amine Chemical class C1CNCCC1NC1=CC=CC=C1 LKRMTUUCKBQGFO-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 238000004634 pharmacological analysis method Methods 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 235000012045 salad Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 150000001420 substituted heterocyclic compounds Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- NZARHKBYDXFVPP-UHFFFAOYSA-N tetrathiolane Chemical compound C1SSSS1 NZARHKBYDXFVPP-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/66—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having a hetero atom as the second substituent in position 4
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (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)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Claims (9)
1. Förfarande för framställning av ett farmaceutiskt pipe-ridinderivat med formeln I 4* V_/ i vilken formel R1 är oxadiazolyl, imidazolyl, triazolyl, tetrazolyl eller tiazolyl, som är osubstituerad eller substituerad, varvid minst en av substituenter är en C^C^alkoxi-Ci-CValkylgrup eller en Q-CValkylgrup; R2 är fenyl eller 2-fluorfenyl; R3 är C,-C4-alkylgrup; och L är 2-fenyletyl, 2-(4-etyl-4,5-dihydro-5-oxo-lH-tetra-zol-l-yl)etyl, bensyl, 2-(2-tienyl)etyl, 2-(3-tienyl)etyl, 2-(lH-pyrazol-l-yl)etyl, 2-(2-pyridinyl)etyl, 2-metylbutyl, 2-etoxietyl, 2-oxo-2-fenyletyl, 2-(4-trifluorometyl)fenyl-etyl, 2-(4-fluorofenyl)etyl, 2-(2-fluorofenyl)etyl, 2-(N-ftalmodo)etyl, 2-metylpropyl, 2-(4-metyltiazol-5-yl)etyl, eller 2-(3,3-dietyl-2,4-(lH,3H)pyridindion-l-yl)etyl, kännetecknat av att (a) man omsätter en förening med vids-täende formeln R'>^n -L R2 - NH"^ \_/ vilken R1, R2 och L är som ovan, med ett acylerande ämne, 2 som är R3(COX) eller (R3CO)20, väri R3 är som ovan och reak- 3 tionsblandningen värmes under reaktionen eller (b) man omsätter en förening med vidstäende formeln 92065 R1 8 \/—\ R1 - C - N--V N - H A* V7 i vilken R1, R2 och R1 är som ovan, med föreningen LX, väri L är som ovan och X är en halogen, och reaktionen utförs i ett inert organiskt lösningsmedel i närvaro av en bas.
2. Förfarande enligt patentkrav 1(a), kännetecknat av att föreningen med formeln (II) frsunställs N - L (II) R2 - HN—\_/ genom omsättning av en piperidon med följande formeln .. Q..> med en amin med formeln R2NH för bildning av en Schiff's bas med följande formeln R2N = ^ - L och genom omsättning av den Schiff's bas med en förening med formeln RLi för bildning av en förening med formeln (II). „.:x> Förfarande enligt patentkrav 1(a), kännetecknat av att föreningen med formeln (II) 92065 bildas genom omsättning av en amin med formeln I^NHjOch ett oorganiskt cyanidsalt med en piperidon med följande formeln L - N y = O för bildning av en cyanmellanprodukt med vidstäende formeln /-\ CN l - n \_/ NHR2 och genom ersättning därefter cyangruppen med en R*-grupp för bildning av en förening med nämnda formel (II).
4. Förfarande enligt patentkrav 3, k&nnetecknat av att substitution utförs genom omsättning av nämnda cyanmellanprodukt med föreningen med formeln R'lii.
5. Förfarande enligt patentkrav 1(b), kannetecknat av att en förening med formeln o Rl,^\ /—\ R3 - C - N-—NH k framställs genom katalytisk hydrering av en förening med formeln (III) , S R3 - C - N-NCI^Ph R2 \-/ eller genom omsättning av föreningen med nämnda formeln (I-II) med alfa-kloretylkloroformat och genom metanolysering därefter av den bildade blandningen, och den nämnda föreningen med formeln (III) framställs med ett förfarande enligt nägot av patentkraven 1-3, varvid L är PhCHj-grupp.
6. Förfarande enligt patentkrav 1(a), kännetecknat av att R1 är tetrazol, R2 är fenyl eller fluorofenyl och L är f e- 92065 nyletyl och att nämnda förening med formeln (II) framställs genom förändring av cyanogruppen i föreningen med följande formeln O'·' Cxi till en tetrazolgrupp.
7. Förfarande enligt patentkrav 6, kännetecknat av att cyan(eller nitril)-gruppen förändras till en tetrazolgrupp i en reaktion med ett azidsalt i ett vattenfritt reaktionsme-dium.
8. Förfarande enligt patentkrav 7, kännetecknat av att azidsaltet är natriumsalt.
9. Förfarande enligt patentkrav 7 eller 8, kännetecknat av att reaktionsmediet är tetrahydrofuran.
10. Förfarande enligt nägot av patentkraven 6-9, kännetecknat av att föreningen med följande formeln O'·* oc bildas genom omsättning av N-fenyletylpiperidon med ett cyanidsalt och med en amin med formeln 11¾¾. M
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13989987 | 1987-12-31 | ||
| US07/139,899 US4791120A (en) | 1987-12-31 | 1987-12-31 | 4-heteropentacyclic-4-[N-(phenyl)amino] piperidine derivatives and pharmaceutical compositions and method employing such compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI886057A FI886057A (sv) | 1989-07-01 |
| FI92065B true FI92065B (sv) | 1994-06-15 |
| FI92065C FI92065C (sv) | 1994-09-26 |
Family
ID=22488798
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI886057A FI92065C (sv) | 1987-12-31 | 1988-12-30 | Förfarande för framställning av farmaceutiska piperidinderivat |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4791120A (sv) |
| JP (1) | JPH01213278A (sv) |
| KR (1) | KR890009921A (sv) |
| CN (1) | CN1023010C (sv) |
| AU (1) | AU616708B2 (sv) |
| DK (1) | DK732888A (sv) |
| FI (1) | FI92065C (sv) |
| IL (1) | IL88645A (sv) |
| NO (1) | NO174553C (sv) |
| NZ (1) | NZ227172A (sv) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4871749A (en) * | 1987-12-31 | 1989-10-03 | Boc, Inc. | 4-heteropentacyclic-4-(N-(phenyl)amido) piperidine derivatives and pharamaceutical compositions and method employing such compounds |
| USRE34201E (en) * | 1989-04-20 | 1993-03-23 | Anaquest, Inc. | N-aryl-N-[4-(1-heterocyclicalkyl)piperidinyl]amides and pharmaceutical compositions and methods employing such compounds |
| US5053411A (en) * | 1989-04-20 | 1991-10-01 | Anaquest, Inc. | N-aryl-N-[4-(1-heterocyclicalkyl)piperidinyl]amides and pharmaceutical compositions and methods employing such compounds |
| US5145967A (en) * | 1989-04-20 | 1992-09-08 | Anaquest, Inc. | Method for preparing 4-alkoxyalkyl-4-phenylaminopiperdines and derivatives thereof |
| FR2725986B1 (fr) * | 1994-10-21 | 1996-11-29 | Adir | Nouveaux derives de piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US6677332B1 (en) | 1999-05-25 | 2004-01-13 | Sepracor, Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| US7361666B2 (en) * | 1999-05-25 | 2008-04-22 | Sepracor, Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| US6635661B2 (en) | 2000-05-25 | 2003-10-21 | Sepracor Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| US6693099B2 (en) * | 2000-10-17 | 2004-02-17 | The Procter & Gamble Company | Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance |
| US6376514B1 (en) | 2000-10-17 | 2002-04-23 | The Procter & Gamble Co. | Substituted six-membered heterocyclic compounds useful for treating multidrug resistance and compositions and methods thereof |
| AU2003277552A1 (en) * | 2002-11-06 | 2004-06-07 | Takeda Pharmaceutical Company Limited | Receptor regulator |
| EP1966140A1 (en) * | 2005-11-17 | 2008-09-10 | Mallinckrodt, Inc. | Process for synthesizing remifentanil |
| RU2612970C1 (ru) * | 2015-10-05 | 2017-03-14 | Федеральное государственное казённое военное образовательное учреждение высшего профессионального образования "Военная академия радиационной, химической и биологической защиты имени Маршала Советского Союза С.К. Тимошенко" г. Кострома Министерства обороны Российской Федерации | Способ получения 1-бензил-4-пропиоанилидо-4-пиперидинкарбонитрила |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE623427A (sv) * | 1961-10-10 | |||
| US3998834A (en) * | 1975-03-14 | 1976-12-21 | Janssen Pharmaceutica N.V. | N-(4-piperidinyl)-n-phenylamides and -carbamates |
| US4584303A (en) * | 1984-04-09 | 1986-04-22 | The Boc Group, Inc. | N-aryl-N-(4-piperidinyl)amides and pharmaceutical compositions and method employing such compounds |
-
1987
- 1987-12-31 US US07/139,899 patent/US4791120A/en not_active Expired - Fee Related
-
1988
- 1988-12-02 NZ NZ227172A patent/NZ227172A/en unknown
- 1988-12-06 AU AU26604/88A patent/AU616708B2/en not_active Ceased
- 1988-12-08 NO NO885463A patent/NO174553C/no unknown
- 1988-12-09 IL IL88645A patent/IL88645A/xx unknown
- 1988-12-28 JP JP63332752A patent/JPH01213278A/ja active Pending
- 1988-12-30 CN CN89100056A patent/CN1023010C/zh not_active Expired - Fee Related
- 1988-12-30 DK DK732888A patent/DK732888A/da not_active Application Discontinuation
- 1988-12-30 FI FI886057A patent/FI92065C/sv not_active IP Right Cessation
- 1988-12-30 KR KR1019880018227A patent/KR890009921A/ko not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NO885463L (no) | 1989-07-03 |
| US4791120A (en) | 1988-12-13 |
| DK732888A (da) | 1989-07-01 |
| KR890009921A (ko) | 1989-08-04 |
| IL88645A0 (en) | 1989-07-31 |
| FI886057A (sv) | 1989-07-01 |
| NO174553C (no) | 1994-05-25 |
| DK732888D0 (da) | 1988-12-30 |
| AU2660488A (en) | 1989-07-13 |
| JPH01213278A (ja) | 1989-08-28 |
| IL88645A (en) | 1993-07-08 |
| CN1035285A (zh) | 1989-09-06 |
| CN1023010C (zh) | 1993-12-08 |
| NO885463D0 (no) | 1988-12-08 |
| FI92065C (sv) | 1994-09-26 |
| NZ227172A (en) | 1990-06-26 |
| AU616708B2 (en) | 1991-11-07 |
| NO174553B (no) | 1994-02-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BB | Publication of examined application | ||
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: BOC, INC. |