BG64126B1 - Заместени бензиламинопиперидини - Google Patents

Заместени бензиламинопиперидини Download PDF

Info

Publication number: BG64126B1
Authority: BG; Bulgaria
Prior art keywords: compound; halogen; trifluoromethyl; methoxy; phenylpiperidine
Prior art date: 1995-08-24

Application number

BG102288A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG102288A (en

Inventor

Kunio Satake

Yuji Shishido

Hiroaki Wakabayashi

Original Assignee

Pfizer Inc.

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

1995-08-24

Filing date

1998-02-27

Publication date

2004-01-30

1998-02-27 Application filed by Pfizer Inc. filed Critical Pfizer Inc.

1998-09-30 Publication of BG102288A publication Critical patent/BG102288A/xx

2004-01-30 Publication of BG64126B1 publication Critical patent/BG64126B1/bg

Links

QACOELYINOMVBY-UHFFFAOYSA-N n-benzylpiperidin-1-amine Chemical class C=1C=CC=CC=1CNN1CCCCC1 QACOELYINOMVBY-UHFFFAOYSA-N 0.000 title claims abstract description 4
-1 halogen-C1-C6-alkoxy Chemical group 0.000 claims abstract description 86
150000003839 salts Chemical class 0.000 claims abstract description 30
229910052736 halogen Inorganic materials 0.000 claims abstract description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
150000002367 halogens Chemical group 0.000 claims abstract description 16
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
208000035475 disorder Diseases 0.000 claims abstract description 12
125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
206010047700 Vomiting Diseases 0.000 claims abstract description 9
230000008673 vomiting Effects 0.000 claims abstract description 9
208000018522 Gastrointestinal disease Diseases 0.000 claims abstract description 8
208000019695 Migraine disease Diseases 0.000 claims abstract description 8
208000002193 Pain Diseases 0.000 claims abstract description 8
208000027866 inflammatory disease Diseases 0.000 claims abstract description 8
230000036407 pain Effects 0.000 claims abstract description 8
201000010099 disease Diseases 0.000 claims abstract description 7
206010042496 Sunburn Diseases 0.000 claims abstract description 6
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
239000001257 hydrogen Substances 0.000 claims abstract description 6
230000033115 angiogenesis Effects 0.000 claims abstract description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
229910052799 carbon Inorganic materials 0.000 claims abstract description 5
150000001721 carbon Chemical group 0.000 claims abstract description 5
206010027599 migraine Diseases 0.000 claims abstract description 5
229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
239000001301 oxygen Substances 0.000 claims abstract description 5
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 5
150000002431 hydrogen Chemical group 0.000 claims abstract description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 3
125000000753 cycloalkyl group Chemical group 0.000 claims abstract 2
150000001875 compounds Chemical class 0.000 claims description 229
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 56
238000002360 preparation method Methods 0.000 claims description 28
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
XQDSIGDVDWFZPP-UHFFFAOYSA-N 2-phenylpiperidin-1-amine Chemical compound NN1CCCCC1C1=CC=CC=C1 XQDSIGDVDWFZPP-UHFFFAOYSA-N 0.000 claims description 14
125000005843 halogen group Chemical group 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 10
210000003169 central nervous system Anatomy 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 6
206010046543 Urinary incontinence Diseases 0.000 claims description 5
230000002411 adverse Effects 0.000 claims description 5
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
UOYMONBFUXQTMB-ZXNYFWILSA-N (2s,3s)-n-[[3-methoxy-8-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl]-2-phenylpiperidin-3-amine Chemical compound C1([C@@H]2NCCC[C@@H]2NCC2=CC=3C(CCCC=3C=C2OC)C(F)(F)F)=CC=CC=C1 UOYMONBFUXQTMB-ZXNYFWILSA-N 0.000 claims description 2
VCXIYDHMYHPBJX-OXJNMPFZSA-N (2S,3S)-3-[[2-methoxy-5-(1,1,3,3,3-pentafluoroprop-1-en-2-yl)phenyl]methyl]-2-phenylpiperidin-1-amine Chemical compound FC(=C(C(F)(F)F)C=1C=CC(=C(C[C@H]2[C@H](N(CCC2)N)C2=CC=CC=C2)C=1)OC)F VCXIYDHMYHPBJX-OXJNMPFZSA-N 0.000 claims 1
230000002265 prevention Effects 0.000 claims 1
208000015114 central nervous system disease Diseases 0.000 abstract description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 5
241000590002 Helicobacter pylori Species 0.000 abstract description 3
229940037467 helicobacter pylori Drugs 0.000 abstract description 3
210000002700 urine Anatomy 0.000 abstract description 2
239000000243 solution Substances 0.000 description 96
238000005160 1H NMR spectroscopy Methods 0.000 description 50
239000000203 mixture Substances 0.000 description 49
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
239000003921 oil Substances 0.000 description 34
235000019198 oils Nutrition 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000012043 crude product Substances 0.000 description 32
229920006395 saturated elastomer Polymers 0.000 description 30
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 29
239000011541 reaction mixture Substances 0.000 description 28
238000000034 method Methods 0.000 description 25
238000005481 NMR spectroscopy Methods 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
239000007787 solid Substances 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
239000011780 sodium chloride Substances 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
238000000746 purification Methods 0.000 description 17
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
238000001816 cooling Methods 0.000 description 15
239000012044 organic layer Substances 0.000 description 15
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
229940125797 compound 12 Drugs 0.000 description 14
150000003053 piperidines Chemical class 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
239000010410 layer Substances 0.000 description 13
239000002904 solvent Substances 0.000 description 13
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 12
239000012458 free base Substances 0.000 description 12
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 11
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 11
TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 11
102100024304 Protachykinin-1 Human genes 0.000 description 11
101800003906 Substance P Proteins 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
229940125851 compound 27 Drugs 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
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239000000725 suspension Substances 0.000 description 11
UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
239000002253 acid Substances 0.000 description 10
239000002585 base Substances 0.000 description 10
239000011734 sodium Substances 0.000 description 10
YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 9
DCGKMADOLVRKCK-UHFFFAOYSA-N 2-phenylpiperidin-1-amine;dihydrochloride Chemical compound Cl.Cl.NN1CCCCC1C1=CC=CC=C1 DCGKMADOLVRKCK-UHFFFAOYSA-N 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
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229940125844 compound 46 Drugs 0.000 description 9
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KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
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UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 7
LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 7
229940125904 compound 1 Drugs 0.000 description 7
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IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
241000124008 Mammalia Species 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
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238000004587 chromatography analysis Methods 0.000 description 6
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FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 6
KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 5
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 5
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 5
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
229940125782 compound 2 Drugs 0.000 description 5
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WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 4
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JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
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Classifications

- 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
- C07D211/56—Nitrogen atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- 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
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Otolaryngology (AREA)
Urology & Nephrology (AREA)
Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

BG102288A 1995-08-24 1998-02-27 Заместени бензиламинопиперидини BG64126B1 (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IB9500683		1995-08-24
PCT/IB1996/000572 WO1997008144A1 (fr)	1995-08-24	1996-06-10	Composes de benzylaminopiperidine substitues

Publications (2)

Publication Number	Publication Date
BG102288A BG102288A (en)	1998-09-30
BG64126B1 true BG64126B1 (bg)	2004-01-30

Family

ID=11004362

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG102288A BG64126B1 (bg)	1995-08-24	1998-02-27	Заместени бензиламинопиперидини

Country Status (41)

Country	Link
US (1)	US6506775B1 (fr)
EP (2)	EP1114817B1 (fr)
JP (1)	JP3084069B2 (fr)
KR (1)	KR100288673B1 (fr)
CN (1)	CN1153764C (fr)
AP (1)	AP643A (fr)
AR (1)	AR006305A1 (fr)
AT (2)	ATE258166T1 (fr)
AU (1)	AU702698B2 (fr)
BG (1)	BG64126B1 (fr)
BR (1)	BR9609989A (fr)
CA (1)	CA2227814C (fr)
CO (1)	CO4480738A1 (fr)
CZ (1)	CZ297543B6 (fr)
DE (2)	DE69616817T2 (fr)
DK (2)	DK1114817T3 (fr)
DZ (1)	DZ2086A1 (fr)
ES (2)	ES2163017T3 (fr)
HR (1)	HRP960386B1 (fr)
HU (1)	HU225480B1 (fr)
IL (1)	IL119078A (fr)
IS (1)	IS1947B (fr)
MA (1)	MA23961A1 (fr)
MX (1)	MX9801467A (fr)
MY (1)	MY114800A (fr)
NO (1)	NO310720B1 (fr)
NZ (1)	NZ308207A (fr)
OA (1)	OA10666A (fr)
PE (2)	PE1398A1 (fr)
PL (1)	PL186773B1 (fr)
PT (2)	PT1114817E (fr)
RO (1)	RO119299B1 (fr)
RU (1)	RU2152930C2 (fr)
SI (2)	SI1114817T1 (fr)
SK (1)	SK282925B6 (fr)
TN (1)	TNSN96107A1 (fr)
TR (1)	TR199800300T1 (fr)
TW (1)	TW340842B (fr)
UA (1)	UA48981C2 (fr)
WO (1)	WO1997008144A1 (fr)
YU (1)	YU49122B (fr)

Families Citing this family (59)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MX9706196A (es) *	1996-08-14	1998-02-28	Pfizer	Compuestos triciclicos de piperidinilamino como antagonistas de la sustancia p.
TW426667B (en) *	1997-11-19	2001-03-21	Pfizer	Piperidinylaminomethyl trifluoromethyl cyclic ether compounds as substance P antagonists
US6777428B1 (en)	1999-02-10	2004-08-17	Eli Lilly And Company	5-HT1f agonist
IL145945A0 (en) *	1999-05-06	2002-07-25	Pfizer Prod Inc	Substituted benzolactam compounds
RS49964B (sr)	1999-05-17	2008-09-29	Pfizer Products Inc.,	Postupak za dobijanje 2-fenil-3-aminopiridina,njegovih supstituisanih fenil derivata, i njegovih soli
EE04719B1 (et) *	1999-05-21	2006-10-16	Pfizer Products Inc.	1-trifluorometüül-4-hüdroksü-7-piperidinüül-aminometüülkromaani derivaadid
DK1095939T3 (da) *	1999-10-18	2004-04-13	Pfizer Prod Inc	Fremgangsmåde til fremstilling af cykliske piperidinylaminomethyltrifluormethyletherforbindelser
CA2324116A1 (fr) *	1999-10-25	2001-04-25	Susan Beth Sobolov-Jaynes	Antagonistes du recepteur nk-1 et eletriptan pour le traitement de la migraine
CA2389306C (fr)	1999-11-03	2010-03-30	Albany Molecular Research, Inc.	Tetrahydroisoquinolines a substitution aryle et heteroaryle et utilisation de ces composes pour bloquer le recaptage de norepinephrine, de dopamine et de serotonine
US7163949B1 (en)	1999-11-03	2007-01-16	Amr Technology, Inc.	4-phenyl substituted tetrahydroisoquinolines and use thereof
BR0112350A (pt)	2000-07-11	2003-06-24	Albany Molecular Res Inc	Composto, composição farmacêutica, e, método de tratar um animal afligido por um distúrbio neurológico ou psicológico
PA8525601A1 (es) *	2000-08-21	2002-04-25	Hoffmann La Roche	Profarmacos de (3s,4s)-4-bencil-1-[2-(4-hidroxi-bencenosulfonil)-etil]-piperidin-3-ol
US20020049211A1 (en) *	2000-09-06	2002-04-25	Sobolov-Jaynes Susan Beth	Combination treatment for depression and anxiety
EP1192952A3 (fr) *	2000-09-28	2003-03-26	Pfizer Products Inc.	Composition pour le traitement de la dépression et de l'anxieté contenant un antagoniste du recepteur NK-3 et un antagoniste du récepteur NK-1
US6911544B2 (en)	2002-10-23	2005-06-28	Pfizer Inc.	Process for the preparation of (S,S)-cis-2-phenyl-3-aminopiperidine
CA2518839A1 (fr)	2003-04-18	2004-11-04	Eli Lilly And Company	Composes (piperidinyloxy)phenyle, (piperidinyloxy)pyridinyle, (piperidinylsulfanyl)phenyle et (piperidinylsulfanyl)pyridinyle utilises comme agonistes des recepteurs 5-ht<sb>1f</sb>
EP1753722A2 (fr) *	2004-05-21	2007-02-21	Pfizer Products Inc.	Metabolites de (+)-(2s, 3s)-3-(2-methoxy-5-trifluoromethoxybenzylamino)-2-phenyl-piperidine
AU2005274927B2 (en)	2004-07-15	2011-11-03	Albany Molecular Research, Inc.	Aryl-and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
ATE550019T1 (de)	2005-05-17	2012-04-15	Merck Sharp & Dohme	Cis-4-ä(4-chlorophenyl)sulfonylü-4-(2,5- difluorophenyl)cyclohexanepropansäure zur behandlug von krebs
JP5258561B2 (ja)	2005-07-15	2013-08-07	アルバニーモレキュラーリサーチ，インコーポレイテッド	アリール置換およびヘテロアリール置換テトラヒドロベンズアゼピンならびにノルエピネフリン、ドーパミンおよびセロトニンの再取り込みを遮断するためのその使用
AU2006297443B2 (en)	2005-09-29	2010-08-12	Merck Sharp & Dohme Corp.	Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators
SE529246C2 (sv) *	2005-10-13	2007-06-12	Neurosearch Sweden Ab	Nya disubstituerade fenyl-piperidiner som modulatorer för dopaminneurotransmission
GB0603041D0 (en)	2006-02-15	2006-03-29	Angeletti P Ist Richerche Bio	Therapeutic compounds
JP5489333B2 (ja)	2006-09-22	2014-05-14	メルク・シャープ・アンド・ドーム・コーポレーション	脂肪酸合成阻害剤を用いた治療の方法
US20110218176A1 (en)	2006-11-01	2011-09-08	Barbara Brooke Jennings-Spring	Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
PL2805945T3 (pl)	2007-01-10	2019-09-30	Msd Italia S.R.L.	Indazole podstawione grupą amidową jako inhibitory polimerazy poli(adp-rybozy) - (parp)
CA2682727C (fr)	2007-04-02	2016-03-22	Banyu Pharmaceutical Co., Ltd.	Derive d'indoledione
CA2690191C (fr)	2007-06-27	2015-07-28	Merck Sharp & Dohme Corp.	Derives de 4-carboxybenzylamino utilises en tant qu'inhibiteurs de l'histone desacetylase
CN102014631A (zh)	2008-03-03	2011-04-13	泰格尔医药科技公司	酪氨酸激酶抑制剂
EP2264029A4 (fr)	2008-03-31	2011-08-24	Kowa Co	Dérivé de 1,3-dihydroisobenzofurane
US9156812B2 (en)	2008-06-04	2015-10-13	Bristol-Myers Squibb Company	Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine
EP2413932A4 (fr)	2009-04-01	2012-09-19	Merck Sharp & Dohme	Inhibiteurs de l'activité akt
ES2528404T3 (es)	2009-05-12	2015-02-10	Bristol-Myers Squibb Company	Formas cristalinas de (S)-7-([1,2,4]triazol[1,5-a]piridin-6-il)-4-(3,4-diclorofenil)-1,2,3,4-tetrahidroisoquinolina y sus usos
WO2010132437A1 (fr)	2009-05-12	2010-11-18	Albany Molecular Research, Inc.	Aryle, hétéroaryle et tétrahydroisoquinolines à hétérocycle substitué et leur utilisation
CN102595902B (zh)	2009-05-12	2015-04-29	阿尔巴尼分子研究公司	7-([1,2,4]三唑并[1,5-a]吡啶-6-基)-4-(3,4-二氯苯基)-1,2,3,4-四氢异喹啉及其用途
NZ599343A (en)	2009-10-14	2014-05-30	Merck Sharp & Dohme	Substituted piperidines that increase p53 activity and the uses thereof
EP2584903B1 (fr)	2010-06-24	2018-10-24	Merck Sharp & Dohme Corp.	Nouveaux composés hétérocycliques utilisés comme inhibiteurs de erk
WO2012018754A2 (fr)	2010-08-02	2012-02-09	Merck Sharp & Dohme Corp.	Inhibition à médiation par interférence arn de caténine (protéine associée à cadhérine), expression du gène bêta 1 (ctnnb1) à l'aide de petit acide nucléique interférent (sian)
EP4079856A1 (fr)	2010-08-17	2022-10-26	Sirna Therapeutics, Inc.	Inhibition médiée par des arn interférents de l'expression génique du virus de l'hépatite b (vhb) à l'aide de petits acides nucléiques interférents (pani)
EP2608669B1 (fr)	2010-08-23	2016-06-22	Merck Sharp & Dohme Corp.	Nouveaux dérivés de pyrazolo[1,5-a]pyrimidine utilisés comme inhibiteurs de mtor
EP2613782B1 (fr)	2010-09-01	2016-11-02	Merck Sharp & Dohme Corp.	Dérivés d'indazole utilisables en tant qu'inhibiteurs de la voie erk
WO2012036997A1 (fr)	2010-09-16	2012-03-22	Schering Corporation	Dérivés condensés de pyrazole utilisés comme nouveaux inhibiteurs erk
ES2663009T3 (es)	2010-10-29	2018-04-10	Sirna Therapeutics, Inc.	Inhibición de la expresión génica mediada por interferencia por ARN utilizando ácidos nucleicos de interferencia cortos (ANic)
EP2654748B1 (fr)	2010-12-21	2016-07-27	Merck Sharp & Dohme Corp.	Dérivés d'indazole utiles en tant qu'inhibiteurs de erk
CA2831730A1 (fr)	2011-04-21	2012-10-26	Piramal Enterprises Limited	Forme cristalline d'un sel d'un derive de morpholinosulfonylindole et son procede de preparation
US9023865B2 (en)	2011-10-27	2015-05-05	Merck Sharp & Dohme Corp.	Compounds that are ERK inhibitors
EP3453762B1 (fr)	2012-05-02	2021-04-21	Sirna Therapeutics, Inc.	Compositions d'acide nucléique interférent court (sina)
US9233979B2 (en)	2012-09-28	2016-01-12	Merck Sharp & Dohme Corp.	Compounds that are ERK inhibitors
WO2014078568A1 (fr)	2012-11-14	2014-05-22	The Johns Hopkins University	Méthodes et compositions pour le traitement de la schizophrénie
BR112015012295A8 (pt)	2012-11-28	2023-03-14	Merck Sharp & Dohme	Uso de um inibidor de wee1, e, kit para identificar um paciente com câncer
BR112015013611A2 (pt)	2012-12-20	2017-11-14	Merck Sharp & Dohme	composto, e, composição farmacêutica
US9540377B2 (en)	2013-01-30	2017-01-10	Merck Sharp & Dohme Corp.	2,6,7,8 substituted purines as HDM2 inhibitors
US20160194368A1 (en)	2013-09-03	2016-07-07	Moderna Therapeutics, Inc.	Circular polynucleotides
US10975084B2 (en)	2016-10-12	2021-04-13	Merck Sharp & Dohme Corp.	KDM5 inhibitors
WO2019094311A1 (fr)	2017-11-08	2019-05-16	Merck Sharp & Dohme Corp.	Inhibiteurs de prmt5
EP3706747B1 (fr)	2017-11-08	2025-09-03	Merck Sharp & Dohme LLC	Inhibiteurs de prmt5
AU2019317549A1 (en)	2018-08-07	2021-02-25	Msd International Gmbh	PRMT5 inhibitors
EP3833667B1 (fr)	2018-08-07	2024-03-13	Merck Sharp & Dohme LLC	Inhibiteurs de prmt5
EP3833668B1 (fr)	2018-08-07	2025-03-19	Merck Sharp & Dohme LLC	Inhibiteurs de prmt5

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5232929A (en) *	1990-11-28	1993-08-03	Pfizer Inc.	3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use
US5364943A (en) *	1991-11-27	1994-11-15	Pfizer Inc.	Preparation of substituted piperidines
JPH0794440B2 (ja) *	1991-03-26	1995-10-11	フアイザー・インコーポレイテツド	置換ピペリジンの立体選択的製造
HU221634B1 (hu) *	1991-06-20	2002-12-28	Pfizer Inc.	Nitrogéntartalmú heterociklusos vegyületek fluor-alkoxi-benzilamino-származékai, eljárás előállításukra és az ezeket tartalmazó gyógyszerkészítmények
US5340826A (en) *	1993-02-04	1994-08-23	Pfizer Inc.	Pharmaceutical agents for treatment of urinary incontinence
US5393762A (en) *	1993-06-04	1995-02-28	Pfizer Inc.	Pharmaceutical agents for treatment of emesis
EP0653208A3 (fr) *	1993-11-17	1995-10-11	Pfizer	Antagonistes de la substance P pour le traitement et la prévention de l'erythème solaire.
EP0655246A1 (fr) *	1993-11-30	1995-05-31	Pfizer Inc.	Antagonistes de la substance P pour le traitement des maladies causées par Helicobacter Pylori ou d'autres bacteries spirales, ureare-positives, gram-négatives
CA2216701A1 (fr)	1995-03-27	1996-10-03	Akira Okayama	Derives de piperidine
ATE223896T1 (de) *	1995-12-21	2002-09-15	Pfizer	3-((5-substituierte benzyl)amino)-2- phenylpiperidine als substance-p-antagonisten
US5990125A (en)	1996-01-19	1999-11-23	Pfizer Inc.	NK-1 receptor antagonists for the treatment of cancer

1996
- 1996-06-04 TW TW085106675A patent/TW340842B/zh active
- 1996-06-10 JP JP09510015A patent/JP3084069B2/ja not_active Expired - Fee Related
- 1996-06-10 TN TNTNSN96107A patent/TNSN96107A1/fr unknown
- 1996-06-10 EP EP01108350A patent/EP1114817B1/fr not_active Expired - Lifetime
- 1996-06-10 CZ CZ0052198A patent/CZ297543B6/cs not_active IP Right Cessation
- 1996-06-10 PL PL96325332A patent/PL186773B1/pl not_active IP Right Cessation
- 1996-06-10 BR BR9609989A patent/BR9609989A/pt not_active Application Discontinuation
- 1996-06-10 SI SI9630670T patent/SI1114817T1/xx unknown
- 1996-06-10 MX MX9801467A patent/MX9801467A/es active IP Right Grant
- 1996-06-10 SK SK207-98A patent/SK282925B6/sk not_active IP Right Cessation
- 1996-06-10 DE DE69616817T patent/DE69616817T2/de not_active Expired - Fee Related
- 1996-06-10 AU AU57769/96A patent/AU702698B2/en not_active Ceased
- 1996-06-10 DK DK01108350T patent/DK1114817T3/da active
- 1996-06-10 ES ES96914375T patent/ES2163017T3/es not_active Expired - Lifetime
- 1996-06-10 CN CNB961965037A patent/CN1153764C/zh not_active Expired - Fee Related
- 1996-06-10 ES ES01108350T patent/ES2211684T3/es not_active Expired - Lifetime
- 1996-06-10 PT PT01108350T patent/PT1114817E/pt unknown
- 1996-06-10 DK DK96914375T patent/DK0861235T3/da active
- 1996-06-10 AT AT01108350T patent/ATE258166T1/de not_active IP Right Cessation
- 1996-06-10 CA CA002227814A patent/CA2227814C/fr not_active Expired - Fee Related
- 1996-06-10 SI SI9630374T patent/SI0861235T1/xx unknown
- 1996-06-10 RU RU98102959/04A patent/RU2152930C2/ru not_active IP Right Cessation
- 1996-06-10 PT PT96914375T patent/PT861235E/pt unknown
- 1996-06-10 EP EP96914375A patent/EP0861235B1/fr not_active Expired - Lifetime
- 1996-06-10 TR TR1998/00300T patent/TR199800300T1/xx unknown
- 1996-06-10 WO PCT/IB1996/000572 patent/WO1997008144A1/fr active IP Right Grant
- 1996-06-10 NZ NZ308207A patent/NZ308207A/en unknown
- 1996-06-10 DE DE69631390T patent/DE69631390T2/de not_active Expired - Fee Related
- 1996-06-10 KR KR1019980701310A patent/KR100288673B1/ko not_active Expired - Fee Related
- 1996-06-10 UA UA98020924A patent/UA48981C2/uk unknown
- 1996-06-10 RO RO98-00334A patent/RO119299B1/ro unknown
- 1996-06-10 HU HU9901159A patent/HU225480B1/hu not_active IP Right Cessation
- 1996-06-10 AT AT96914375T patent/ATE208377T1/de not_active IP Right Cessation
- 1996-08-15 IL IL11907896A patent/IL119078A/xx not_active IP Right Cessation
- 1996-08-20 AR ARP960104045A patent/AR006305A1/es active IP Right Grant
- 1996-08-21 PE PE1996000625A patent/PE1398A1/es not_active Application Discontinuation
- 1996-08-21 PE PE2001000276A patent/PE20010700A1/es not_active Application Discontinuation
- 1996-08-21 DZ DZ960130A patent/DZ2086A1/fr active
- 1996-08-22 HR HR960386A patent/HRP960386B1/xx not_active IP Right Cessation
- 1996-08-23 MY MYPI96003496A patent/MY114800A/en unknown
- 1996-08-23 YU YU47896A patent/YU49122B/sh unknown
- 1996-08-23 MA MA24339A patent/MA23961A1/fr unknown
- 1996-08-24 AP APAP/P/1996/000850A patent/AP643A/en active
- 1996-08-26 CO CO96045248A patent/CO4480738A1/es unknown
1997
- 1997-12-30 IS IS4644A patent/IS1947B/is unknown
1998
- 1998-02-23 NO NO19980751A patent/NO310720B1/no unknown
- 1998-02-23 OA OA9800023A patent/OA10666A/en unknown
- 1998-02-27 BG BG102288A patent/BG64126B1/bg unknown
2000
- 2000-05-01 US US09/564,398 patent/US6506775B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
SK282925B6 (sk)	2003-01-09
CA2227814C (fr)	2002-12-31
YU49122B (sh)	2004-03-12
OA10666A (en)	2002-11-25
US6506775B1 (en)	2003-01-14
DZ2086A1 (fr)	2002-07-22
DK0861235T3 (da)	2001-12-27
SI1114817T1 (en)	2004-06-30
CA2227814A1 (fr)	1997-03-06
EP0861235B1 (fr)	2001-11-07
CO4480738A1 (es)	1997-07-09
PL325332A1 (en)	1998-07-20
KR19990044077A (ko)	1999-06-25
JPH10510554A (ja)	1998-10-13
IS1947B (is)	2004-10-13
JP3084069B2 (ja)	2000-09-04
PE1398A1 (es)	1998-02-27
TW340842B (en)	1998-09-21
PT1114817E (pt)	2004-05-31
CN1153764C (zh)	2004-06-16
AP9600850A0 (en)	1996-10-31
PE20010700A1 (es)	2001-07-09
TNSN96107A1 (fr)	2005-03-15
YU47896A (sh)	1998-12-23
MX9801467A (es)	1998-05-31
IL119078A0 (en)	1996-11-14
TR199800300T1 (xx)	1998-06-22
WO1997008144A1 (fr)	1997-03-06
NO310720B1 (no)	2001-08-20
KR100288673B1 (ko)	2001-05-02
AP643A (en)	1998-04-24
IS4644A (is)	1997-12-30
AU5776996A (en)	1997-03-19
PT861235E (pt)	2002-03-28
HK1014935A1 (en)	1999-10-08
UA48981C2 (uk)	2002-09-16
CN1193961A (zh)	1998-09-23
ATE208377T1 (de)	2001-11-15
DK1114817T3 (da)	2004-04-26
SK20798A3 (en)	1999-03-12
SI0861235T1 (en)	2002-04-30
AU702698B2 (en)	1999-03-04
NZ308207A (en)	1998-07-28
MA23961A1 (fr)	1997-04-01
NO980751D0 (no)	1998-02-23
AR006305A1 (es)	1999-08-25
BG102288A (en)	1998-09-30
DE69631390T2 (de)	2004-11-25
EP1114817B1 (fr)	2004-01-21
HU225480B1 (en)	2006-12-28
DE69631390D1 (de)	2004-02-26
HRP960386B1 (en)	2002-04-30
CZ52198A3 (cs)	1999-01-13
IL119078A (en)	2003-11-23
MY114800A (en)	2003-01-31
HUP9901159A3 (en)	2000-05-29
BR9609989A (pt)	1999-07-06
ES2211684T3 (es)	2004-07-16
DE69616817D1 (de)	2001-12-13
EP1114817A1 (fr)	2001-07-11
ES2163017T3 (es)	2002-01-16
HUP9901159A2 (hu)	1999-07-28
HRP960386A2 (en)	1998-04-30
DE69616817T2 (de)	2002-04-04
NO980751L (no)	1998-02-23
ATE258166T1 (de)	2004-02-15
RO119299B1 (ro)	2004-07-30
CZ297543B6 (cs)	2007-02-07
PL186773B1 (pl)	2004-02-27
EP0861235A1 (fr)	1998-09-02
RU2152930C2 (ru)	2000-07-20

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