JP4865113B2 - ピペリジン誘導体の製法 - Google Patents
ピペリジン誘導体の製法 Download PDFInfo
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- JP4865113B2 JP4865113B2 JP52309597A JP52309597A JP4865113B2 JP 4865113 B2 JP4865113 B2 JP 4865113B2 JP 52309597 A JP52309597 A JP 52309597A JP 52309597 A JP52309597 A JP 52309597A JP 4865113 B2 JP4865113 B2 JP 4865113B2
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- Prior art keywords
- formula
- derivative
- hydrogen
- moiety
- compound
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 28
- 150000003053 piperidines Chemical class 0.000 title claims description 64
- -1 piperidine derivative compound Chemical class 0.000 claims abstract description 216
- 239000001257 hydrogen Substances 0.000 claims abstract description 106
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 106
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 90
- 238000000034 method Methods 0.000 claims abstract description 87
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 74
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 61
- 150000002367 halogens Chemical class 0.000 claims abstract description 61
- 125000003118 aryl group Chemical group 0.000 claims abstract description 58
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 32
- 125000001424 substituent group Chemical group 0.000 claims abstract description 32
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 25
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 54
- 239000002243 precursor Substances 0.000 claims description 50
- 150000005172 methylbenzenes Chemical class 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 35
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical class CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 claims description 27
- 229910052710 silicon Inorganic materials 0.000 claims description 26
- 239000010703 silicon Substances 0.000 claims description 25
- 238000005917 acylation reaction Methods 0.000 claims description 22
- 150000001412 amines Chemical class 0.000 claims description 22
- 230000010933 acylation Effects 0.000 claims description 18
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 229910000272 alkali metal oxide Inorganic materials 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 15
- 238000007069 methylation reaction Methods 0.000 claims description 14
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 13
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 13
- 230000011987 methylation Effects 0.000 claims description 13
- 230000009466 transformation Effects 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 7
- 230000001035 methylating effect Effects 0.000 claims description 6
- 239000012022 methylating agents Substances 0.000 claims description 5
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims 11
- 230000003301 hydrolyzing effect Effects 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
- 239000002904 solvent Substances 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- 239000000203 mixture Substances 0.000 description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- 239000000243 solution Substances 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 20
- 229960000351 terfenadine Drugs 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 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 17
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 14
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Chemical class 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 150000003839 salts Chemical class 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
- 0 CC1(*)CCN(C)CC1 Chemical compound CC1(*)CCN(C)CC1 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical class CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 12
- 125000000468 ketone group Chemical group 0.000 description 12
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 238000005804 alkylation reaction Methods 0.000 description 11
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 239000004215 Carbon black (E152) Substances 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 229930195733 hydrocarbon Natural products 0.000 description 9
- 150000002430 hydrocarbons Chemical class 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 150000008282 halocarbons Chemical class 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 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 7
- 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
- 229910052799 carbon Inorganic materials 0.000 description 7
- 239000002207 metabolite Substances 0.000 description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 125000003944 tolyl group Chemical group 0.000 description 7
- 125000005023 xylyl group Chemical group 0.000 description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-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
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000002524 organometallic group Chemical group 0.000 description 6
- XMGMFRIEKMMMSU-UHFFFAOYSA-N phenylmethylbenzene Chemical group C=1C=CC=CC=1[C]C1=CC=CC=C1 XMGMFRIEKMMMSU-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 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
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 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 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 150000007522 mineralic acids Chemical class 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
- 239000012044 organic layer Substances 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 4
- 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 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 4
- 150000008041 alkali metal carbonates Chemical class 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 206010003119 arrhythmia Diseases 0.000 description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 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
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-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
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 230000006793 arrhythmia Effects 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- 125000006267 biphenyl group Chemical group 0.000 description 3
- 150000001721 carbon Chemical group 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
- 238000001816 cooling Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229940071870 hydroiodic acid Drugs 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
- 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 3
- ULWORPZJUIFPIC-UHFFFAOYSA-N methyl 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)C1=CC=C(C(=O)CCCCl)C=C1 ULWORPZJUIFPIC-UHFFFAOYSA-N 0.000 description 3
- GOUQSHOAAGQXNJ-UHFFFAOYSA-N methyl 2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoate Chemical compound C1=CC(C(C)(C)C(=O)OC)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GOUQSHOAAGQXNJ-UHFFFAOYSA-N 0.000 description 3
- PGQMZSGBFIPEKX-UHFFFAOYSA-N methyl 2-[4-[4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butanoyl]phenyl]-2-methylpropanoate Chemical compound C1=CC(C(C)(C)C(=O)OC)=CC=C1C(=O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 PGQMZSGBFIPEKX-UHFFFAOYSA-N 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
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Classifications
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- 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
- C07D211/36—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
- C07D211/54—Sulfur 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/575,344 | 1995-12-21 | ||
| US08/575,344 US6201124B1 (en) | 1995-12-21 | 1995-12-21 | Process for production of piperidine derivatives |
| PCT/US1996/020769 WO1997022344A1 (en) | 1995-12-21 | 1996-12-19 | Process for production of piperidine derivatives |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008227513A Division JP2009019059A (ja) | 1995-12-21 | 2008-09-04 | ピペリジン誘導体の製法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2000502105A JP2000502105A (ja) | 2000-02-22 |
| JP2000502105A5 JP2000502105A5 (cg-RX-API-DMAC7.html) | 2004-11-04 |
| JP4865113B2 true JP4865113B2 (ja) | 2012-02-01 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52309597A Expired - Lifetime JP4865113B2 (ja) | 1995-12-21 | 1996-12-19 | ピペリジン誘導体の製法 |
| JP2008227513A Pending JP2009019059A (ja) | 1995-12-21 | 2008-09-04 | ピペリジン誘導体の製法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008227513A Pending JP2009019059A (ja) | 1995-12-21 | 2008-09-04 | ピペリジン誘導体の製法 |
Country Status (16)
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|---|---|
| US (7) | US6201124B1 (cg-RX-API-DMAC7.html) |
| EP (2) | EP0877733B1 (cg-RX-API-DMAC7.html) |
| JP (2) | JP4865113B2 (cg-RX-API-DMAC7.html) |
| KR (2) | KR100591212B1 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE335726T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU723759B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BR9612099A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2240735C (cg-RX-API-DMAC7.html) |
| DE (1) | DE69636439T2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK0877733T3 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2268715T3 (cg-RX-API-DMAC7.html) |
| HU (1) | HUP9900947A3 (cg-RX-API-DMAC7.html) |
| NO (1) | NO311718B1 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ326228A (cg-RX-API-DMAC7.html) |
| PT (1) | PT877733E (cg-RX-API-DMAC7.html) |
| WO (1) | WO1997022344A1 (cg-RX-API-DMAC7.html) |
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| HU226037B1 (en) * | 1993-06-25 | 2008-03-28 | Aventis Inc | Process for producing antihistaminic 4-diphenylmethyl/diphenylmethoxy piperidine derivatives and novel intermediates |
| US6153754A (en) * | 1995-12-21 | 2000-11-28 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| US6201124B1 (en) * | 1995-12-21 | 2001-03-13 | 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. |
| US20030021849A1 (en) * | 2001-04-09 | 2003-01-30 | Ben-Zion Dolitzky | Polymorphs of fexofenadine hydrochloride |
| KR20040012747A (ko) * | 2001-04-09 | 2004-02-11 | 테바 파마슈티컬 인더스트리즈 리미티드 | 펙소페나딘 염산염의 다형체 |
| 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 |
| EP1453509A2 (en) * | 2001-11-08 | 2004-09-08 | Teva Pharmaceutical Industries Ltd. | Polymorphs of fexofenadine base |
| JP2005532356A (ja) * | 2002-06-10 | 2005-10-27 | 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 | 塩酸フェキソフェナジンの多型体ｘｖｉ |
| US6949765B2 (en) | 2002-11-05 | 2005-09-27 | Chartered Semiconductor Manufacturing Ltd. | Padless structure design for easy identification of bridging defects in lines by passive voltage contrast |
| 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 |
| US7498345B2 (en) | 2004-09-17 | 2009-03-03 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| WO2006037042A1 (en) * | 2004-09-28 | 2006-04-06 | Teva Pharmaceutical Industries Ltd. | Fexofenadine crystal form and processes for its preparation thereof |
| RU2008122978A (ru) | 2005-11-09 | 2009-12-20 | Комбинаторкс, Инкорпорейтед (Us) | Способы, композиции и наборы для лечения медицинских состояний |
| CN100443470C (zh) * | 2006-07-21 | 2008-12-17 | 杭州保灵有限公司 | 一种依巴斯汀的制备方法 |
| ITMI20061492A1 (it) * | 2006-07-27 | 2008-01-28 | Archimica Srl | Processo per la preparazione di fexofenadina. |
| ITMI20061491A1 (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 |
| US20110130711A1 (en) * | 2009-11-19 | 2011-06-02 | Follica, Inc. | Hair growth treatment |
| EP2371817A1 (en) * | 2010-04-01 | 2011-10-05 | Arevipharma GmbH | Process for the preparation of 1-[4-(1,1-dimethylethyl)phenyl]-4-[4-(diphenylmethoxy)-1-piperidinyl]-1-butanone and acid addition salts thereof |
| CN105254579A (zh) * | 2015-09-19 | 2016-01-20 | 万全万特制药江苏有限公司 | 一种一锅法制备比拉斯汀中间体的方法 |
| CN114621083A (zh) * | 2022-03-30 | 2022-06-14 | 西安万隆制药股份有限公司 | 一种抗组胺药物盐酸非索非那定杂质及其合成方法和应用 |
| CN114671802B (zh) * | 2022-04-14 | 2024-05-17 | 江苏联环药业股份有限公司 | 一种高纯度依巴斯汀的制备方法 |
| EP4647423A1 (en) * | 2023-01-03 | 2025-11-12 | Chengdu Shibeikang Biomedical Technology Co., Ltd. | Crystal form and amorphous form of carebastine p-toluenesulfonate |
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| US3839431A (en) | 1970-07-13 | 1974-10-01 | Squibb & Sons Inc | Cyclopropylmethylphenylacetic acids and derivatives |
| US3787217A (en) * | 1970-12-25 | 1974-01-22 | Kumiai Chemical Industry Co | Method for controlling sea organisms |
| US3898271A (en) | 1971-06-08 | 1975-08-05 | Squibb & Sons Inc | Cyclopropylmethylphenylacetic acids and derivatives |
| BE794598A (fr) | 1972-01-28 | 1973-05-16 | Richardson Merrell Inc | Nouveaux derives olefiniques de piperidines substituees en 4 et leur procede de preparation |
| 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 |
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| DD141422A5 (de) | 1978-01-27 | 1980-04-30 | Schering Ag | Verfahren zur herstellung von phenylessigsaeure-derivaten |
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| 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 |
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| CA2141572C (en) | 1992-08-03 | 2001-02-06 | James W. Young | Terfenadine metabolites and their optically pure isomers for treating allergic disorders |
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| US20020007068A1 (en) * | 1999-07-16 | 2002-01-17 | D'ambra Thomas E. | Piperidine derivatives and process for their production |
| 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 |
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-
1995
- 1995-12-21 US US08/575,344 patent/US6201124B1/en not_active Expired - Lifetime
-
1996
- 1996-12-19 JP JP52309597A patent/JP4865113B2/ja not_active Expired - Lifetime
- 1996-12-19 BR BR9612099-1A patent/BR9612099A/pt not_active IP Right Cessation
- 1996-12-19 EP EP96945097A patent/EP0877733B1/en not_active Expired - Lifetime
- 1996-12-19 HU HU9900947A patent/HUP9900947A3/hu unknown
- 1996-12-19 PT PT96945097T patent/PT877733E/pt unknown
- 1996-12-19 DE DE69636439T patent/DE69636439T2/de not_active Expired - Lifetime
- 1996-12-19 CA CA002240735A patent/CA2240735C/en not_active Expired - Lifetime
- 1996-12-19 WO PCT/US1996/020769 patent/WO1997022344A1/en not_active Ceased
- 1996-12-19 KR KR1020057009030A patent/KR100591212B1/ko not_active Expired - Lifetime
- 1996-12-19 ES ES96945097T patent/ES2268715T3/es not_active Expired - Lifetime
- 1996-12-19 AU AU13547/97A patent/AU723759B2/en not_active Expired
- 1996-12-19 KR KR10-1998-0704760A patent/KR100516869B1/ko not_active Expired - Lifetime
- 1996-12-19 AT AT96945097T patent/ATE335726T1/de active
- 1996-12-19 NZ NZ326228A patent/NZ326228A/en not_active IP Right Cessation
- 1996-12-19 DK DK96945097T patent/DK0877733T3/da active
- 1996-12-19 EP EP03077248A patent/EP1362849A3/en not_active Withdrawn
-
1998
- 1998-06-18 NO NO19982806A patent/NO311718B1/no not_active IP Right Cessation
-
2000
- 2000-08-09 US US09/634,775 patent/US6448406B1/en not_active Expired - Lifetime
- 2000-08-09 US US09/634,169 patent/US6452011B1/en not_active Expired - Lifetime
-
2002
- 2002-08-05 US US10/212,854 patent/US6974872B2/en not_active Expired - Fee Related
-
2005
- 2005-05-06 US US11/123,275 patent/US7560561B2/en not_active Expired - Fee Related
-
2008
- 2008-09-04 JP JP2008227513A patent/JP2009019059A/ja active Pending
-
2009
- 2009-06-11 US US12/483,002 patent/US8022220B2/en not_active Expired - Fee Related
-
2011
- 2011-08-11 US US13/207,850 patent/US20110295014A1/en not_active Abandoned
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