ZA200204289B - Substituted 1 and 2 naphthol mannich bases. - Google Patents
Substituted 1 and 2 naphthol mannich bases. Download PDFInfo
- Publication number
- ZA200204289B ZA200204289B ZA200204289A ZA200204289A ZA200204289B ZA 200204289 B ZA200204289 B ZA 200204289B ZA 200204289 A ZA200204289 A ZA 200204289A ZA 200204289 A ZA200204289 A ZA 200204289A ZA 200204289 B ZA200204289 B ZA 200204289B
- Authority
- ZA
- South Africa
- Prior art keywords
- radical
- phenyl
- radicals
- aryl
- substituted
- Prior art date
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- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 title claims description 170
- KJCVRFUGPWSIIH-UHFFFAOYSA-N alpha-naphthol Natural products C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 title claims description 98
- 229950011260 betanaphthol Drugs 0.000 title claims description 85
- RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 title claims description 79
- 150000003254 radicals Chemical class 0.000 claims description 276
- -1 heteroaryl radical Chemical class 0.000 claims description 183
- 125000003118 aryl group Chemical group 0.000 claims description 78
- 150000004782 1-naphthols Chemical class 0.000 claims description 70
- 238000002360 preparation method Methods 0.000 claims description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 239000003814 drug Substances 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 150000005840 aryl radicals Chemical class 0.000 claims description 38
- 239000000243 solution Substances 0.000 claims description 35
- 150000001875 compounds Chemical class 0.000 claims description 30
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 29
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 28
- 229910052794 bromium Inorganic materials 0.000 claims description 27
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 24
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 15
- 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 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 15
- 239000012346 acetyl chloride Substances 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 14
- 150000007975 iminium salts Chemical class 0.000 claims description 14
- 230000036407 pain Effects 0.000 claims description 13
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 238000000746 purification Methods 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 8
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 150000003335 secondary amines Chemical class 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 6
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 208000007848 Alcoholism Diseases 0.000 claims description 5
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 5
- 206010012735 Diarrhoea Diseases 0.000 claims description 5
- 206010013654 Drug abuse Diseases 0.000 claims description 5
- 208000007882 Gastritis Diseases 0.000 claims description 5
- 208000010412 Glaucoma Diseases 0.000 claims description 5
- 206010020751 Hypersensitivity Diseases 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 208000025865 Ulcer Diseases 0.000 claims description 5
- 206010046543 Urinary incontinence Diseases 0.000 claims description 5
- 206010001584 alcohol abuse Diseases 0.000 claims description 5
- 208000025746 alcohol use disease Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- JKWMSGQKBLHBQQ-UHFFFAOYSA-N diboron trioxide Chemical compound O=BOB=O JKWMSGQKBLHBQQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 201000003631 narcolepsy Diseases 0.000 claims description 5
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 230000035939 shock Effects 0.000 claims description 5
- 208000011117 substance-related disease Diseases 0.000 claims description 5
- 229930192474 thiophene Natural products 0.000 claims description 5
- 231100000397 ulcer Toxicity 0.000 claims description 5
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 4
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 150000004786 2-naphthols Chemical class 0.000 claims description 3
- KRTGJZMJJVEKRX-UHFFFAOYSA-N 2-phenylethan-1-yl Chemical compound [CH2]CC1=CC=CC=C1 KRTGJZMJJVEKRX-UHFFFAOYSA-N 0.000 claims description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
- VVZADSMBUOMIGD-UHFFFAOYSA-N 4-[dimethylamino(phenyl)methyl]-3-hydroxynaphthalene-2-carboxylic acid Chemical compound OC=1C(C(O)=O)=CC2=CC=CC=C2C=1C(N(C)C)C1=CC=CC=C1 VVZADSMBUOMIGD-UHFFFAOYSA-N 0.000 claims description 3
- ZQVRRAFLJWZFHX-UHFFFAOYSA-N 6-[dimethylamino(phenyl)methyl]-5-hydroxynaphthalene-1-sulfonamide Chemical compound C=1C=C2C(S(N)(=O)=O)=CC=CC2=C(O)C=1C(N(C)C)C1=CC=CC=C1 ZQVRRAFLJWZFHX-UHFFFAOYSA-N 0.000 claims description 3
- 229920002536 Scavenger resin Polymers 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 238000007796 conventional method Methods 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- JENKBNCZGROHRS-UHFFFAOYSA-N methyl 4-[dimethylamino(phenyl)methyl]-3-hydroxynaphthalene-2-carboxylate Chemical compound OC=1C(C(=O)OC)=CC2=CC=CC=C2C=1C(N(C)C)C1=CC=CC=C1 JENKBNCZGROHRS-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 125000004188 dichlorophenyl group Chemical group 0.000 claims 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims 2
- 125000003944 tolyl group Chemical group 0.000 claims 2
- SOHOMVZGRJOXDG-UHFFFAOYSA-N 1-[dimethylamino(phenyl)methyl]naphthalen-2-ol Chemical compound OC=1C=CC2=CC=CC=C2C=1C(N(C)C)C1=CC=CC=C1 SOHOMVZGRJOXDG-UHFFFAOYSA-N 0.000 claims 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 claims 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 1
- OZBVAEZOKDPKIY-UHFFFAOYSA-N 3-propylbenzenethiol Chemical compound CCCC1=CC=CC(S)=C1 OZBVAEZOKDPKIY-UHFFFAOYSA-N 0.000 claims 1
- URRLYUGLJFIWRT-UHFFFAOYSA-N CN(C)C(C1=C2C=CC(=CC2=CC=C1O)C(=O)O)C1=CC=CC=C1.CN(C)C(C1=C(C(=CC2=CC(=CC=C12)OC)C(=O)O)O)C1=CC=CC=C1 Chemical compound CN(C)C(C1=C2C=CC(=CC2=CC=C1O)C(=O)O)C1=CC=CC=C1.CN(C)C(C1=C(C(=CC2=CC(=CC=C12)OC)C(=O)O)O)C1=CC=CC=C1 URRLYUGLJFIWRT-UHFFFAOYSA-N 0.000 claims 1
- FNFFOQPSUHOEEH-UHFFFAOYSA-N CN(C)C(c1ccccc1)c1cc(N)c2ccccc2c1O.CN(C)C(c1ccccc1)c1c(O)c(cc2ccccc12)C(=O)NN Chemical compound CN(C)C(c1ccccc1)c1cc(N)c2ccccc2c1O.CN(C)C(c1ccccc1)c1c(O)c(cc2ccccc12)C(=O)NN FNFFOQPSUHOEEH-UHFFFAOYSA-N 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- LQSIIDUEQLESNE-UHFFFAOYSA-M sodium;4-[dimethylamino(phenyl)methyl]-3-hydroxy-7-methoxynaphthalene-2-carboxylate Chemical compound [Na+].OC=1C(C([O-])=O)=CC2=CC(OC)=CC=C2C=1C(N(C)C)C1=CC=CC=C1 LQSIIDUEQLESNE-UHFFFAOYSA-M 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 description 89
- 238000003786 synthesis reaction Methods 0.000 description 87
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 40
- NNUFCPXGFRLSRB-UHFFFAOYSA-M benzylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CC1=CC=CC=C1 NNUFCPXGFRLSRB-UHFFFAOYSA-M 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 10
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- JVXJSWKEEBJQDG-UHFFFAOYSA-M 1-[(2-methoxyphenyl)methylidene]piperidin-1-ium;chloride Chemical compound [Cl-].COC1=CC=CC=C1C=[N+]1CCCCC1 JVXJSWKEEBJQDG-UHFFFAOYSA-M 0.000 description 6
- SSGKVPHXOGUKEU-UHFFFAOYSA-M 4-[(2-methoxyphenyl)methylidene]morpholin-4-ium;chloride Chemical compound [Cl-].COC1=CC=CC=C1C=[N+]1CCOCC1 SSGKVPHXOGUKEU-UHFFFAOYSA-M 0.000 description 6
- UNFNRIIETORURP-UHFFFAOYSA-N 7-methoxynaphthalen-2-ol Chemical compound C1=CC(O)=CC2=CC(OC)=CC=C21 UNFNRIIETORURP-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- DERGWVDOVNNILN-UHFFFAOYSA-M 1-[(2-methylphenyl)methylidene]piperidin-1-ium;chloride Chemical compound [Cl-].CC1=CC=CC=C1C=[N+]1CCCCC1 DERGWVDOVNNILN-UHFFFAOYSA-M 0.000 description 5
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- ZMWUARBYWJOZCB-UHFFFAOYSA-M 4-[(2,3-dimethoxyphenyl)methylidene]morpholin-4-ium;chloride Chemical compound [Cl-].COC1=CC=CC(C=[N+]2CCOCC2)=C1OC ZMWUARBYWJOZCB-UHFFFAOYSA-M 0.000 description 4
- XKDINSWAEFDFGD-UHFFFAOYSA-M 4-[(2-methylphenyl)methylidene]morpholin-4-ium;chloride Chemical compound [Cl-].CC1=CC=CC=C1C=[N+]1CCOCC1 XKDINSWAEFDFGD-UHFFFAOYSA-M 0.000 description 4
- LVSPDZAGCBEQAV-UHFFFAOYSA-N 4-chloronaphthalen-1-ol Chemical compound C1=CC=C2C(O)=CC=C(Cl)C2=C1 LVSPDZAGCBEQAV-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- 230000036592 analgesia Effects 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 4
- OKXKGBZOUANTMR-UHFFFAOYSA-M (2-methoxyphenyl)methylidene-dimethylazanium;chloride Chemical compound [Cl-].COC1=CC=CC=C1C=[N+](C)C OKXKGBZOUANTMR-UHFFFAOYSA-M 0.000 description 3
- NQLCGLIHNZVNFG-UHFFFAOYSA-M 1-[(2-chlorophenyl)methylidene]piperidin-1-ium;chloride Chemical compound [Cl-].ClC1=CC=CC=C1C=[N+]1CCCCC1 NQLCGLIHNZVNFG-UHFFFAOYSA-M 0.000 description 3
- WWPKRXOOVICNJY-UHFFFAOYSA-N 6-methoxynaphthalen-2-ol Chemical compound C1=C(O)C=CC2=CC(OC)=CC=C21 WWPKRXOOVICNJY-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 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
- 238000001514 detection method Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- ZGZBVRRPMNQEDK-UHFFFAOYSA-N 1-(3-bromo-1,4-dimethoxynaphthalen-2-yl)propan-2-ol Chemical compound C1=CC=C2C(OC)=C(Br)C(CC(C)O)=C(OC)C2=C1 ZGZBVRRPMNQEDK-UHFFFAOYSA-N 0.000 description 2
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 2
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- 230000020341 sensory perception of pain Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- IGPAQQGMTQUIIT-UHFFFAOYSA-M sodium;4-[dimethylamino(phenyl)methyl]-3-hydroxy-7-methoxynaphthalene-1-carboxylate Chemical compound [Na+].OC=1C=C(C([O-])=O)C2=CC(OC)=CC=C2C=1C(N(C)C)C1=CC=CC=C1 IGPAQQGMTQUIIT-UHFFFAOYSA-M 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960003107 tramadol hydrochloride Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/48—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups
- C07C215/50—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/58—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/26—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C219/28—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton having amino groups bound to acyclic carbon atoms of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/02—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton
- C07C225/14—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated
- C07C225/16—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/38—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/48—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring being part of a condensed ring system of the same carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/38—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to carbon atoms of six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Silver Salt Photography Or Processing Solution Therefor (AREA)
- Ceramic Products (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19963179A DE19963179B4 (de) | 1999-12-27 | 1999-12-27 | Substituierte 1- und 2-Naphthol-Mannichbasen |
Publications (1)
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ZA200204289B true ZA200204289B (en) | 2004-02-10 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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ZA200204289A ZA200204289B (en) | 1999-12-27 | 2002-05-29 | Substituted 1 and 2 naphthol mannich bases. |
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US (2) | US6774136B2 (cs) |
EP (1) | EP1246790B1 (cs) |
JP (1) | JP2003519115A (cs) |
KR (1) | KR20020062334A (cs) |
CN (1) | CN1247523C (cs) |
AT (1) | ATE294773T1 (cs) |
AU (1) | AU775709B2 (cs) |
BR (1) | BR0016781A (cs) |
CA (1) | CA2394098A1 (cs) |
CO (1) | CO5251380A1 (cs) |
CZ (1) | CZ20022240A3 (cs) |
DE (2) | DE19963179B4 (cs) |
DK (1) | DK1246790T3 (cs) |
ES (1) | ES2241688T3 (cs) |
HK (1) | HK1051845A1 (cs) |
HU (1) | HUP0203732A3 (cs) |
IL (1) | IL149920A (cs) |
MX (1) | MXPA02005865A (cs) |
NO (1) | NO20022896D0 (cs) |
NZ (1) | NZ519976A (cs) |
PE (1) | PE20010986A1 (cs) |
PL (1) | PL356523A1 (cs) |
PT (1) | PT1246790E (cs) |
RU (1) | RU2002120479A (cs) |
SK (1) | SK8532002A3 (cs) |
UY (1) | UY26507A1 (cs) |
WO (1) | WO2001047866A1 (cs) |
ZA (1) | ZA200204289B (cs) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
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DE102005033732B4 (de) * | 2005-05-27 | 2014-02-13 | Grünenthal GmbH | Trennung stereoisomerer N,N-Dialkylamino-2-alkyl-3-hydroxy-3-phenyl-alkane |
ATE509925T1 (de) | 2006-11-17 | 2011-06-15 | Pfizer | Substituierte bicyclocarbonsäureamidverbindungen |
CN104592090A (zh) | 2010-02-23 | 2015-05-06 | 康奈尔大学 | 脯氨酰羟化酶抑制剂及其使用方法 |
US8883850B2 (en) | 2010-05-28 | 2014-11-11 | Merck Sharp & Dohme Corp. | Naphthalene carboxamide M1 receptor positive allosteric modulators |
CN103193676B (zh) * | 2013-04-18 | 2014-03-19 | 安徽工业大学 | 一锅法合成1-氨甲酸酯基烷基-2-萘酚的方法 |
CN103664826B (zh) * | 2014-01-07 | 2016-06-29 | 西北师范大学 | 一种氨基萘酚类化合物的制备方法 |
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Publication number | Priority date | Publication date | Assignee | Title |
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AU4458996A (en) * | 1995-01-20 | 1996-08-07 | Nippon Shinyaku Co. Ltd. | Ethylamine derivatives and drugs |
DE19805370A1 (de) * | 1997-03-14 | 1998-09-17 | Gruenenthal Gmbh | Substituierte Aminoverbindungen und ihre Verwendung als analgetisch wirksame Substanzen |
WO1998058928A1 (fr) * | 1997-06-23 | 1998-12-30 | Yoshitomi Pharmaceutical Industries, Ltd. | Agent prophylactique ou therapeutique contre des maladies attribuables a une infection par des helicobacters |
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1999
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2000
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2002
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2003
- 2003-04-09 HK HK03102524A patent/HK1051845A1/xx not_active IP Right Cessation
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2004
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