NO311717B1 - Fremgangsmåte for fremstilling av piperidinderivater - Google Patents
Fremgangsmåte for fremstilling av piperidinderivater Download PDFInfo
- Publication number
- NO311717B1 NO311717B1 NO19982770A NO982770A NO311717B1 NO 311717 B1 NO311717 B1 NO 311717B1 NO 19982770 A NO19982770 A NO 19982770A NO 982770 A NO982770 A NO 982770A NO 311717 B1 NO311717 B1 NO 311717B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- group
- hydrogen
- disubstituted
- derivative
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 85
- 230000008569 process Effects 0.000 title claims abstract description 18
- 150000003053 piperidines Chemical class 0.000 title claims description 54
- 238000002360 preparation method Methods 0.000 title claims description 29
- -1 piperidine derivative compounds Chemical class 0.000 claims abstract description 90
- 239000001257 hydrogen Substances 0.000 claims abstract description 84
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 84
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 69
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 55
- 150000002367 halogens Chemical class 0.000 claims abstract description 54
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 50
- 125000001424 substituent group Chemical group 0.000 claims abstract description 41
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 17
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 14
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 100
- 238000006243 chemical reaction Methods 0.000 claims description 56
- 150000001875 compounds Chemical class 0.000 claims description 53
- 239000002253 acid Substances 0.000 claims description 52
- 239000002243 precursor Substances 0.000 claims description 51
- 125000000732 arylene group Chemical group 0.000 claims description 34
- 238000005917 acylation reaction Methods 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 230000010933 acylation Effects 0.000 claims description 19
- 150000001412 amines Chemical class 0.000 claims description 15
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 15
- 125000002524 organometallic group Chemical group 0.000 claims description 14
- 238000005859 coupling reaction Methods 0.000 claims description 13
- 238000007069 methylation reaction Methods 0.000 claims description 12
- 150000003459 sulfonic acid esters Chemical class 0.000 claims description 12
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 11
- 229910000272 alkali metal oxide Inorganic materials 0.000 claims description 11
- UKXSKSHDVLQNKG-UHFFFAOYSA-N benzilic acid Chemical class C=1C=CC=CC=1C(O)(C(=O)O)C1=CC=CC=C1 UKXSKSHDVLQNKG-UHFFFAOYSA-N 0.000 claims description 11
- 238000005658 halogenation reaction Methods 0.000 claims description 11
- 230000011987 methylation Effects 0.000 claims description 11
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 8
- 230000026030 halogenation Effects 0.000 claims description 8
- 239000012022 methylating agents Substances 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 4
- 230000032050 esterification Effects 0.000 claims description 3
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- 230000009466 transformation Effects 0.000 claims 3
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 15
- 238000004519 manufacturing process Methods 0.000 abstract description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 55
- 239000002904 solvent Substances 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 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 23
- 239000000243 solution Substances 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 229960000351 terfenadine Drugs 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000002585 base Substances 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 14
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000008096 xylene Substances 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 12
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 238000005804 alkylation reaction Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 229910001868 water Inorganic materials 0.000 description 11
- 125000000468 ketone group Chemical group 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- 239000004215 Carbon black (E152) Substances 0.000 description 9
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 9
- 229930195733 hydrocarbon Natural products 0.000 description 9
- 150000002430 hydrocarbons Chemical class 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 229910052710 silicon Inorganic materials 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- ZEUXAIYYDDCIRX-UHFFFAOYSA-N losartan carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 ZEUXAIYYDDCIRX-UHFFFAOYSA-N 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 239000010703 silicon Substances 0.000 description 8
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 7
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 150000008282 halocarbons Chemical class 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000003944 tolyl group Chemical group 0.000 description 6
- 125000005023 xylyl group Chemical group 0.000 description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
- VBTJEFSCACXENO-UHFFFAOYSA-N 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)C1=CC=C(C(=O)CCCCl)C=C1 VBTJEFSCACXENO-UHFFFAOYSA-N 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 5
- 239000002841 Lewis acid Substances 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 5
- 150000008041 alkali metal carbonates Chemical class 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 150000007517 lewis acids Chemical class 0.000 description 5
- 150000005172 methylbenzenes Chemical class 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 239000012038 nucleophile Substances 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000005456 alcohol based solvent Substances 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 206010003119 arrhythmia Diseases 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 229940071870 hydroiodic acid Drugs 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
- HRVZFJDYABWCQS-UHFFFAOYSA-N 2-[(4-bromophenyl)methyl]-4,4-dimethyl-1,2-oxazolidine Chemical compound C1C(C)(C)CON1CC1=CC=C(Br)C=C1 HRVZFJDYABWCQS-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical class NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 description 3
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 3
- 150000002334 glycols Chemical class 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 230000033444 hydroxylation Effects 0.000 description 3
- 238000005805 hydroxylation reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- 230000001035 methylating effect Effects 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- UWCWUCKPEYNDNV-LBPRGKRZSA-N 2,6-dimethyl-n-[[(2s)-pyrrolidin-2-yl]methyl]aniline Chemical compound CC1=CC=CC(C)=C1NC[C@H]1NCCC1 UWCWUCKPEYNDNV-LBPRGKRZSA-N 0.000 description 2
- NTZHXKLMSWWUPY-UHFFFAOYSA-N 2-[4-(4-chloro-1-hydroxybutyl)phenyl]-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)C1=CC=C(C(O)CCCCl)C=C1 NTZHXKLMSWWUPY-UHFFFAOYSA-N 0.000 description 2
- LMPCSCOVKHFVKE-UHFFFAOYSA-N 2-[4-[1-hydroxy-4-[4-[hydroxy-bis(4-methylphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid Chemical compound C1=CC(C)=CC=C1C(O)(C=1C=CC(C)=CC=1)C1CCN(CCCC(O)C=2C=CC(=CC=2)C(C)(C)C(O)=O)CC1 LMPCSCOVKHFVKE-UHFFFAOYSA-N 0.000 description 2
- NGAKDIWPTMPPFP-UHFFFAOYSA-N 2-[4-[4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butanoyl]phenyl]-2-methylpropanoic acid Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(=O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 NGAKDIWPTMPPFP-UHFFFAOYSA-N 0.000 description 2
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 210000001567 regular cardiac muscle cell of ventricle Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 150000003377 silicon compounds Chemical class 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- 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
-
- 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
-
- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
-
- 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/576,068 US6153754A (en) | 1995-12-21 | 1995-12-21 | Process for production of piperidine derivatives |
| PCT/US1996/020189 WO1997023213A1 (en) | 1995-12-21 | 1996-12-19 | Process for production of piperidine derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO982770D0 NO982770D0 (no) | 1998-06-16 |
| NO982770L NO982770L (no) | 1998-06-16 |
| NO311717B1 true NO311717B1 (no) | 2002-01-14 |
Family
ID=24302845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19982770A NO311717B1 (no) | 1995-12-21 | 1998-06-16 | Fremgangsmåte for fremstilling av piperidinderivater |
Country Status (15)
| Country | Link |
|---|---|
| US (7) | US6153754A (ja) |
| EP (1) | EP0868182B1 (ja) |
| JP (2) | JP4865114B2 (ja) |
| KR (2) | KR100573943B1 (ja) |
| AT (1) | ATE248595T1 (ja) |
| AU (1) | AU723231B2 (ja) |
| BR (1) | BR9612216A (ja) |
| CA (1) | CA2240927C (ja) |
| DE (1) | DE69629831T2 (ja) |
| DK (1) | DK0868182T3 (ja) |
| ES (1) | ES2206618T3 (ja) |
| NO (1) | NO311717B1 (ja) |
| NZ (1) | NZ326085A (ja) |
| PT (1) | PT868182E (ja) |
| WO (1) | WO1997023213A1 (ja) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU226037B1 (en) * | 1993-06-25 | 2008-03-28 | Aventis Inc | Process for producing antihistaminic 4-diphenylmethyl/diphenylmethoxy piperidine derivatives and novel intermediates |
| US6201124B1 (en) | 1995-12-21 | 2001-03-13 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| US6153754A (en) * | 1995-12-21 | 2000-11-28 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| ES2151442B1 (es) * | 1999-01-11 | 2001-07-01 | Espanola Prod Quimicos | Nuevo derivado del bencenoetanol. |
| WO2002069254A2 (en) * | 2001-02-22 | 2002-09-06 | Classen Immunotherapies, Inc. | Improved algorithms and methods for products safety |
| PL366576A1 (en) * | 2001-04-09 | 2005-02-07 | Teva Pharmaceutical Industries Ltd. | Polymorphs of fexofenadine hydrochloride |
| US20030021849A1 (en) * | 2001-04-09 | 2003-01-30 | Ben-Zion Dolitzky | Polymorphs of fexofenadine hydrochloride |
| ITRM20010260A1 (it) | 2001-05-17 | 2002-11-18 | Dinamite Dipharma S P A In For | Processo per la preparazione della fexofenadina o acido 4 1-idrossi-4-4- (idrossidifenilmetil)-1-piperidinil|-butil|-alfa,alfa-dimetilbenz |
| US7700779B2 (en) | 2001-06-18 | 2010-04-20 | Dr. Reddy's Laboratories Limited | Crystalline forms of fexofenadine and its hydrochloride |
| CZ20033358A3 (en) * | 2001-06-18 | 2004-04-14 | Dr. Reddy's Laboratories Ltd. | Novel crystalline forms of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl] -1-hydroxybutyl] -a,a-dimethylbenzene acetic acid and its hydrochloride |
| TWI263497B (en) * | 2002-03-29 | 2006-10-11 | Lilly Co Eli | Pyridinoylpiperidines as 5-HT1F agonists |
| US20040044038A1 (en) * | 2002-06-10 | 2004-03-04 | Barnaba Krochmal | Polymorphic form XVI of fexofenadine hydrochloride |
| TW200517114A (en) | 2003-10-15 | 2005-06-01 | Combinatorx Inc | Methods and reagents for the treatment of immunoinflammatory disorders |
| EP1628959A2 (en) * | 2004-04-26 | 2006-03-01 | Teva Pharmaceutical Industries Ltd | Crystalline forms of fexofenadine hydrochloride and processes for their preparation |
| US7498443B2 (en) * | 2004-09-17 | 2009-03-03 | Albany Molecular Research, Inc. | Process for production of carebastine |
| JP2008514641A (ja) * | 2004-09-28 | 2008-05-08 | テバ ファーマシューティカル インダストリーズ リミティド | 結晶形フェキソフェナジン、およびその調製方法 |
| EP1956906A4 (en) | 2005-11-09 | 2009-12-30 | Combinatorx Inc | METHODS, COMPOSITIONS AND KITS FOR THE TREATMENT OF PATHOLOGIES |
| ITMI20061492A1 (it) * | 2006-07-27 | 2008-01-28 | Archimica Srl | Processo per la preparazione di fexofenadina. |
| ITMI20070987A1 (it) | 2007-05-16 | 2008-11-17 | Dipharma Francis Srl | Procedimento per la preparazione di composti chetonici |
| US20100092479A1 (en) * | 2008-08-18 | 2010-04-15 | Combinatorx (Singapore) Pte. Ltd. | Compositions and methods for treatment of viral diseases |
| EP2289867A3 (en) | 2009-08-19 | 2012-04-25 | Jubilant Organosys Limited | A process for producing 4-(4-halo-1-oxybutyl)-alpha,alpha-dimethylbenzene acetic acid or alkyl esters thereof |
| US20110130711A1 (en) * | 2009-11-19 | 2011-06-02 | Follica, Inc. | Hair growth treatment |
| SI3545906T1 (sl) | 2013-08-14 | 2021-04-30 | Mitral Valve Technologies Sarl | Sestav nadomestne srčne zaklopke |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2919274A (en) * | 1957-09-17 | 1959-12-29 | Sahyun Melville | Amidines |
| US4028404A (en) * | 1967-07-31 | 1977-06-07 | Allen & Hanburys Limited | Acetic acid derivatives |
| GB1242169A (en) * | 1969-04-09 | 1971-08-11 | Ucb Sa | Piperidine derivatives |
| US3839431A (en) * | 1970-07-13 | 1974-10-01 | Squibb & Sons Inc | Cyclopropylmethylphenylacetic acids and derivatives |
| US3898271A (en) * | 1971-06-08 | 1975-08-05 | Squibb & Sons Inc | Cyclopropylmethylphenylacetic acids and derivatives |
| US3965257A (en) * | 1972-01-28 | 1976-06-22 | Richardson-Merrell Inc. | Compositions and methods for the treatment of the symptoms of histamine induced allergic reactions |
| US3806526A (en) * | 1972-01-28 | 1974-04-23 | Richardson Merrell Inc | 1-aroylalkyl-4-diphenylmethyl piperidines |
| US3878217A (en) * | 1972-01-28 | 1975-04-15 | Richardson Merrell Inc | Alpha-aryl-4-substituted piperidinoalkanol derivatives |
| BE794596A (fr) * | 1972-01-28 | 1973-05-16 | Richardson Merrell Inc | Piperidinoalcanone-oximes substituees et leur procede de preparation |
| BE794598A (fr) * | 1972-01-28 | 1973-05-16 | Richardson Merrell Inc | Nouveaux derives olefiniques de piperidines substituees en 4 et leur procede de preparation |
| US3941795A (en) * | 1974-02-08 | 1976-03-02 | Richardson-Merrell Inc. | α-ARYL-4-SUBSTITUTED PIPERIDINOALKANOL DERIVATIVES |
| US3931197A (en) * | 1974-02-08 | 1976-01-06 | Richardson-Merrell Inc. | Substituted piperidine derivatives |
| US3946022A (en) * | 1974-03-04 | 1976-03-23 | Richardson-Merrell Inc. | Piperidine derivatives |
| US3922276A (en) * | 1974-12-11 | 1975-11-25 | Robins Co Inc A H | 1-Substituted-4-benzylidenepiperidines |
| US3956296A (en) * | 1974-12-11 | 1976-05-11 | A. H. Robins Company, Incorporated | 1-Substituted-4-benzylpiperidines |
| DD141422A5 (de) * | 1978-01-27 | 1980-04-30 | Schering Ag | Verfahren zur herstellung von phenylessigsaeure-derivaten |
| US4254130A (en) * | 1979-04-10 | 1981-03-03 | Richardson-Merrell Inc. | Piperidine derivatives |
| US4285958A (en) * | 1979-04-10 | 1981-08-25 | Richardson-Merrell Inc. | 1-Piperidine-alkylene ketones, pharmaceutical compositions thereof and method of use thereof |
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| GB8321157D0 (en) * | 1983-08-05 | 1983-09-07 | Fordonal Sa | Piperidine derivatives |
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| FR2636946B1 (fr) * | 1988-09-23 | 1990-11-02 | Lipha | ((diarylmethoxy)alcoyl)-1 pyrrolidines et piperidines, procedes de preparation et medicaments les contenant |
| DE4034218A1 (de) | 1990-10-27 | 1992-04-30 | Merck Patent Gmbh | Verfahren zur herstellung von carebastin |
| HU211019B (en) * | 1991-12-02 | 1995-09-28 | Richter Gedeon Vegyeszet | Process for producing new 1,2,3,6-tetrahydropyridine and piperidine derivatives substituted with n-(hydroxylalkyl) group and compositions comprising such compounds |
| MX9302076A (es) * | 1992-04-10 | 1994-03-31 | Merrell Dow Pharma | Proceso novedoso para preparar derivados de piperidina. |
| ES2257757T3 (es) * | 1992-08-03 | 2006-08-01 | Sepracor Inc. | Carboxilato de terfenadina y el tratamiento de trastornos alergicos. |
| US20020007068A1 (en) | 1999-07-16 | 2002-01-17 | D'ambra Thomas E. | Piperidine derivatives and process for their production |
| JP3034047B2 (ja) | 1993-06-24 | 2000-04-17 | オールバニー・モレキュラー・リサーチ・インコーポレイテッド | ピペリジン誘導体及びそれらの製造法 |
| HU226037B1 (en) * | 1993-06-25 | 2008-03-28 | Aventis Inc | Process for producing antihistaminic 4-diphenylmethyl/diphenylmethoxy piperidine derivatives and novel intermediates |
| US6201124B1 (en) | 1995-12-21 | 2001-03-13 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| AU1335897A (en) | 1995-12-21 | 1997-07-17 | Du Pont Merck Pharmaceutical Company, The | Isoxazoline, isothiazoline and pyrazoline factor xa inhibitors |
| US6153754A (en) | 1995-12-21 | 2000-11-28 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| US5925761A (en) * | 1997-02-04 | 1999-07-20 | Sepracor Inc. | Synthesis of terfenadine and derivatives |
| US7498345B2 (en) | 2004-09-17 | 2009-03-03 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
-
1995
- 1995-12-21 US US08/576,068 patent/US6153754A/en not_active Expired - Lifetime
-
1996
- 1996-12-19 BR BR9612216-1A patent/BR9612216A/pt not_active Application Discontinuation
- 1996-12-19 KR KR1020057009028A patent/KR100573943B1/ko not_active IP Right Cessation
- 1996-12-19 JP JP52379097A patent/JP4865114B2/ja not_active Expired - Lifetime
- 1996-12-19 DK DK96944868T patent/DK0868182T3/da active
- 1996-12-19 PT PT96944868T patent/PT868182E/pt unknown
- 1996-12-19 KR KR10-1998-0704759A patent/KR100516868B1/ko not_active IP Right Cessation
- 1996-12-19 AU AU13371/97A patent/AU723231B2/en not_active Expired
- 1996-12-19 ES ES96944868T patent/ES2206618T3/es not_active Expired - Lifetime
- 1996-12-19 AT AT96944868T patent/ATE248595T1/de active
- 1996-12-19 NZ NZ326085A patent/NZ326085A/en not_active IP Right Cessation
- 1996-12-19 CA CA002240927A patent/CA2240927C/en not_active Expired - Lifetime
- 1996-12-19 EP EP96944868A patent/EP0868182B1/en not_active Expired - Lifetime
- 1996-12-19 DE DE69629831T patent/DE69629831T2/de not_active Expired - Lifetime
- 1996-12-19 WO PCT/US1996/020189 patent/WO1997023213A1/en not_active Application Discontinuation
-
1998
- 1998-06-16 NO NO19982770A patent/NO311717B1/no not_active IP Right Cessation
-
2000
- 2000-08-09 US US09/634,983 patent/US6444824B1/en not_active Expired - Lifetime
- 2000-08-09 US US09/637,127 patent/US6458958B1/en not_active Expired - Lifetime
-
2002
- 2002-08-05 US US10/212,829 patent/US6919458B2/en not_active Expired - Fee Related
-
2005
- 2005-05-06 US US11/123,511 patent/US20050209279A1/en not_active Abandoned
-
2006
- 2006-09-15 US US11/521,820 patent/US7678915B2/en not_active Expired - Fee Related
-
2008
- 2008-09-04 JP JP2008227504A patent/JP2009019058A/ja active Pending
-
2010
- 2010-01-13 US US12/686,516 patent/US8476445B2/en not_active Expired - Fee Related
Also Published As
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| Publication | Publication Date | Title |
|---|---|---|
| NO311717B1 (no) | Fremgangsmåte for fremstilling av piperidinderivater | |
| US6201124B1 (en) | Process for production of piperidine derivatives | |
| MXPA98004894A (en) | Procedure for the production of piperid derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |