KR20040027870A - Mch 선택적인 안타고니스트로서의 치환 아닐린 피페리딘 - Google Patents
Mch 선택적인 안타고니스트로서의 치환 아닐린 피페리딘 Download PDFInfo
- Publication number
- KR20040027870A KR20040027870A KR10-2004-7000087A KR20047000087A KR20040027870A KR 20040027870 A KR20040027870 A KR 20040027870A KR 20047000087 A KR20047000087 A KR 20047000087A KR 20040027870 A KR20040027870 A KR 20040027870A
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- phenyl
- branched
- straight
- alkyl
- 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.)
- Ceased
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- 239000005557 antagonist Substances 0.000 title claims abstract description 31
- 150000003053 piperidines Chemical class 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 385
- 150000001875 compounds Chemical class 0.000 claims abstract description 342
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
- 239000003937 drug carrier Substances 0.000 claims abstract description 12
- -1 cyclopentanyl Chemical group 0.000 claims description 225
- 239000000203 mixture Substances 0.000 claims description 137
- 125000000217 alkyl group Chemical group 0.000 claims description 105
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 96
- 125000003118 aryl group Chemical group 0.000 claims description 85
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 80
- 125000001072 heteroaryl group Chemical group 0.000 claims description 75
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 72
- 125000001246 bromo group Chemical group Br* 0.000 claims description 71
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 68
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 60
- 208000035475 disorder Diseases 0.000 claims description 48
- 208000019901 Anxiety disease Diseases 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 30
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 29
- 230000036506 anxiety Effects 0.000 claims description 28
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 27
- 239000007787 solid Substances 0.000 claims description 27
- 208000008589 Obesity Diseases 0.000 claims description 26
- 235000020824 obesity Nutrition 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 20
- 230000004580 weight loss Effects 0.000 claims description 20
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 17
- 239000007788 liquid Substances 0.000 claims description 16
- 208000024891 symptom Diseases 0.000 claims description 14
- 230000027939 micturition Effects 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 9
- 206010020853 Hypertonic bladder Diseases 0.000 claims description 8
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 8
- 208000020629 overactive bladder Diseases 0.000 claims description 8
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 239000000829 suppository Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- 101150104680 MCH1 gene Proteins 0.000 claims 4
- 101100382379 Rattus norvegicus Cap1 gene Proteins 0.000 claims 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims 1
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 333
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 260
- 239000000047 product Substances 0.000 description 189
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 170
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 142
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 140
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 134
- 238000005481 NMR spectroscopy Methods 0.000 description 119
- 239000000243 solution Substances 0.000 description 111
- 239000011541 reaction mixture Substances 0.000 description 99
- JETGTGYZDUEQTF-UHFFFAOYSA-N 2-methyl-n-(3-piperidin-4-ylphenyl)propanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCNCC2)=C1 JETGTGYZDUEQTF-UHFFFAOYSA-N 0.000 description 82
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 81
- 238000012746 preparative thin layer chromatography Methods 0.000 description 72
- 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 70
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 65
- 101800002739 Melanin-concentrating hormone Proteins 0.000 description 62
- 102000047659 melanin-concentrating hormone Human genes 0.000 description 62
- 239000003921 oil Substances 0.000 description 60
- 235000019198 oils Nutrition 0.000 description 60
- ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 59
- 239000000377 silicon dioxide Substances 0.000 description 59
- 235000019439 ethyl acetate Nutrition 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- 239000002904 solvent Substances 0.000 description 49
- 238000004587 chromatography analysis Methods 0.000 description 48
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 48
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 48
- 230000015572 biosynthetic process Effects 0.000 description 41
- 238000003786 synthesis reaction Methods 0.000 description 41
- 239000012267 brine Substances 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 239000012043 crude product Substances 0.000 description 37
- 239000010410 layer Substances 0.000 description 36
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 35
- 239000012044 organic layer Substances 0.000 description 35
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 35
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 34
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 34
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000000284 extract Substances 0.000 description 32
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 31
- 125000000753 cycloalkyl group Chemical group 0.000 description 31
- 230000002829 reductive effect Effects 0.000 description 31
- 239000000725 suspension Substances 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 28
- 125000003342 alkenyl group Chemical group 0.000 description 28
- 125000000392 cycloalkenyl group Chemical group 0.000 description 27
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 27
- 229920005989 resin Polymers 0.000 description 27
- 239000011347 resin Substances 0.000 description 27
- 125000000304 alkynyl group Chemical group 0.000 description 26
- 239000011734 sodium Substances 0.000 description 25
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 22
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 22
- 238000004809 thin layer chromatography Methods 0.000 description 21
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 20
- 238000000746 purification Methods 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 19
- 108020003175 receptors Proteins 0.000 description 19
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 18
- 102000005962 receptors Human genes 0.000 description 18
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 17
- 229910052786 argon Inorganic materials 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 241000700159 Rattus Species 0.000 description 16
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 16
- 235000009518 sodium iodide Nutrition 0.000 description 16
- 208000016261 weight loss Diseases 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 15
- LNVITZUWWUEILI-HSZRJFAPSA-N n-[3-[1-[(3r)-3-hydroxy-3-phenylpropyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CC[C@@H](O)C=3C=CC=CC=3)CC2)=C1 LNVITZUWWUEILI-HSZRJFAPSA-N 0.000 description 15
- 230000002485 urinary effect Effects 0.000 description 15
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- 230000005856 abnormality Effects 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 12
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 12
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- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 12
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- 230000003197 catalytic effect Effects 0.000 description 11
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
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- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 10
- 125000004103 aminoalkyl group Chemical group 0.000 description 10
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- 238000003756 stirring Methods 0.000 description 10
- BLCXBCYVCDPFEU-UHFFFAOYSA-N 4-(4-chlorophenoxy)benzaldehyde Chemical compound C1=CC(Cl)=CC=C1OC1=CC=C(C=O)C=C1 BLCXBCYVCDPFEU-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
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- 208000026935 allergic disease Diseases 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- 230000009610 hypersensitivity Effects 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
- SMFFZOQLHYIRDA-UHFFFAOYSA-N 3,4-dimethoxyphenol Chemical compound COC1=CC=C(O)C=C1OC SMFFZOQLHYIRDA-UHFFFAOYSA-N 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
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- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 8
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 8
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- PDAZPKYSSKIZGN-UHFFFAOYSA-N n-[3-[1-[3-(4-bromophenyl)-3-hydroxypropyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CCC(O)C=3C=CC(Br)=CC=3)CC2)=C1 PDAZPKYSSKIZGN-UHFFFAOYSA-N 0.000 description 7
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- PGMDHKOCPXCMBL-UHFFFAOYSA-N 2-(3-methylbutoxy)naphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(C=O)C(OCCC(C)C)=CC=C21 PGMDHKOCPXCMBL-UHFFFAOYSA-N 0.000 description 6
- JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical compound CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 description 6
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 6
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
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- 241000699670 Mus sp. Species 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
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- 239000003480 eluent Substances 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 235000012631 food intake Nutrition 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 125000003386 piperidinyl group Chemical group 0.000 description 6
- 229920000728 polyester Polymers 0.000 description 6
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- AGKLVMVJXDFIGC-UHFFFAOYSA-N tert-butyl 3-phenylprop-2-enoate Chemical compound CC(C)(C)OC(=O)C=CC1=CC=CC=C1 AGKLVMVJXDFIGC-UHFFFAOYSA-N 0.000 description 1
- RWTHEKXCENZVLI-UHFFFAOYSA-N tert-butyl 4-(3-acetamidophenyl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(=O)NC1=CC=CC(C=2CCN(CC=2)C(=O)OC(C)(C)C)=C1 RWTHEKXCENZVLI-UHFFFAOYSA-N 0.000 description 1
- OTFSYSDFFIZFPA-UHFFFAOYSA-N tert-butyl 4-(3-acetamidophenyl)piperidine-1-carboxylate Chemical compound CC(=O)NC1=CC=CC(C2CCN(CC2)C(=O)OC(C)(C)C)=C1 OTFSYSDFFIZFPA-UHFFFAOYSA-N 0.000 description 1
- VVDCRJGWILREQH-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(B2OC(C)(C)C(C)(C)O2)=C1 VVDCRJGWILREQH-UHFFFAOYSA-N 0.000 description 1
- PKYRLRVLXYAKPM-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenyl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C=CC(=CC=2)[N+]([O-])=O)=C1 PKYRLRVLXYAKPM-UHFFFAOYSA-N 0.000 description 1
- ISDZBATWANXXCN-UHFFFAOYSA-N tert-butyl 4-[3-(2-oxopyrrolidin-1-yl)phenyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=CC(N2C(CCC2)=O)=C1 ISDZBATWANXXCN-UHFFFAOYSA-N 0.000 description 1
- AEVMNSMWKABNOC-UHFFFAOYSA-N tert-butyl 4-[3-(4-chlorobutanoylamino)phenyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=CC(NC(=O)CCCCl)=C1 AEVMNSMWKABNOC-UHFFFAOYSA-N 0.000 description 1
- ULBJIVZLRYKWAD-UHFFFAOYSA-N tert-butyl 4-[3-(propanoylamino)phenyl]piperidine-1-carboxylate Chemical compound CCC(=O)NC1=CC=CC(C2CCN(CC2)C(=O)OC(C)(C)C)=C1 ULBJIVZLRYKWAD-UHFFFAOYSA-N 0.000 description 1
- ONORMRHQQDIGRT-UHFFFAOYSA-N tert-butyl 4-[6-(2-methylpropanoylamino)pyridin-2-yl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)C(=O)NC1=CC=CC(C=2CCN(CC=2)C(=O)OC(C)(C)C)=N1 ONORMRHQQDIGRT-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- NHURGMJVQTWHPE-UHFFFAOYSA-N tert-butyl n-[1-(3,4-difluorophenyl)-2-hydroxyethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CO)C1=CC=C(F)C(F)=C1 NHURGMJVQTWHPE-UHFFFAOYSA-N 0.000 description 1
- OZLMUCOAIWEYRW-UHFFFAOYSA-N tert-butyl n-[3-[4-(3-acetamidophenyl)-3,6-dihydro-2h-pyridin-1-yl]propyl]carbamate Chemical compound CC(=O)NC1=CC=CC(C=2CCN(CCCNC(=O)OC(C)(C)C)CC=2)=C1 OZLMUCOAIWEYRW-UHFFFAOYSA-N 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
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Classifications
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon 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
- C07D211/08—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
- C07D211/30—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 doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—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 doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
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- 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
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- 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
- C07D211/26—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 nitrogen atoms
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- 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
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- C07D211/26—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 nitrogen atoms
- C07D211/28—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 nitrogen atoms to which a second hetero atom is attached
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- 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
- C07D211/80—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 two double bonds between ring members or between ring members and non-ring members
- C07D211/84—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 two 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 directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89979401A | 2001-07-05 | 2001-07-05 | |
| US09/899,794 | 2001-07-05 | ||
| US4258202A | 2002-01-09 | 2002-01-09 | |
| US10/042,582 | 2002-01-09 | ||
| PCT/US2002/021063 WO2003004027A1 (en) | 2001-07-05 | 2002-07-03 | Substituted anilinic piperidines as mch selective antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20040027870A true KR20040027870A (ko) | 2004-04-01 |
Family
ID=26719414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2004-7000087A Ceased KR20040027870A (ko) | 2001-07-05 | 2002-07-03 | Mch 선택적인 안타고니스트로서의 치환 아닐린 피페리딘 |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP1411942A4 (https=) |
| JP (1) | JP2004536104A (https=) |
| KR (1) | KR20040027870A (https=) |
| CN (1) | CN1671386A (https=) |
| CA (1) | CA2454613A1 (https=) |
| CO (1) | CO5670352A2 (https=) |
| EA (1) | EA005934B1 (https=) |
| HU (1) | HUP0401880A2 (https=) |
| IL (1) | IL159697A0 (https=) |
| IS (1) | IS7085A (https=) |
| MX (1) | MXPA03011886A (https=) |
| NO (1) | NO20040028L (https=) |
| NZ (1) | NZ530221A (https=) |
| PL (1) | PL366624A1 (https=) |
| WO (1) | WO2003004027A1 (https=) |
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| FR2850379B1 (fr) * | 2003-01-28 | 2006-11-17 | Aventis Pharma Sa | Produits n-aryl-heteroaromatiques, compositions les contenant et utilisation |
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| EP3083601B1 (en) * | 2013-12-20 | 2020-09-09 | Esteve Pharmaceuticals, S.A. | Piperidine derivatives having multimodal activity against pain |
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| US11072602B2 (en) | 2016-12-06 | 2021-07-27 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
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| WO2020167701A1 (en) | 2019-02-13 | 2020-08-20 | Merck Sharp & Dohme Corp. | Pyrrolidine orexin receptor agonists |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9810671D0 (en) * | 1998-05-18 | 1998-07-15 | Pfizer Ltd | Anti-pruritic agents |
| GB9912413D0 (en) * | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| JP2004502423A (ja) * | 2000-07-05 | 2004-01-29 | シナプティック・ファーマスーティカル・コーポレーション | ヒトメラニン濃縮ホルモン受容体(mch1)をコードするdna及びその使用 |
-
2002
- 2002-07-03 EP EP02746843A patent/EP1411942A4/en not_active Withdrawn
- 2002-07-03 MX MXPA03011886A patent/MXPA03011886A/es not_active Application Discontinuation
- 2002-07-03 EA EA200400146A patent/EA005934B1/ru not_active IP Right Cessation
- 2002-07-03 JP JP2003510038A patent/JP2004536104A/ja not_active Withdrawn
- 2002-07-03 HU HU0401880A patent/HUP0401880A2/hu unknown
- 2002-07-03 WO PCT/US2002/021063 patent/WO2003004027A1/en not_active Ceased
- 2002-07-03 PL PL02366624A patent/PL366624A1/xx not_active Application Discontinuation
- 2002-07-03 CN CNA028172124A patent/CN1671386A/zh active Pending
- 2002-07-03 NZ NZ530221A patent/NZ530221A/xx unknown
- 2002-07-03 CA CA002454613A patent/CA2454613A1/en not_active Abandoned
- 2002-07-03 KR KR10-2004-7000087A patent/KR20040027870A/ko not_active Ceased
- 2002-07-03 IL IL15969702A patent/IL159697A0/xx unknown
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2003
- 2003-12-18 IS IS7085A patent/IS7085A/is unknown
-
2004
- 2004-01-05 NO NO20040028A patent/NO20040028L/no not_active Application Discontinuation
- 2004-02-02 CO CO04007748A patent/CO5670352A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EA005934B1 (ru) | 2005-08-25 |
| EP1411942A4 (en) | 2005-01-26 |
| EP1411942A1 (en) | 2004-04-28 |
| AU2002316531B2 (en) | 2007-09-13 |
| CN1671386A (zh) | 2005-09-21 |
| CA2454613A1 (en) | 2003-01-16 |
| CO5670352A2 (es) | 2006-08-31 |
| JP2004536104A (ja) | 2004-12-02 |
| NZ530221A (en) | 2006-03-31 |
| NO20040028L (no) | 2004-03-04 |
| MXPA03011886A (es) | 2005-03-07 |
| HUP0401880A2 (hu) | 2005-01-28 |
| WO2003004027A1 (en) | 2003-01-16 |
| IS7085A (is) | 2003-12-18 |
| EA200400146A1 (ru) | 2004-08-26 |
| PL366624A1 (en) | 2005-02-07 |
| IL159697A0 (en) | 2004-06-20 |
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