ZA200109794B - Method of inhibiting amyloid protein aggregation and imaging amyloid deposits. - Google Patents
Method of inhibiting amyloid protein aggregation and imaging amyloid deposits. Download PDFInfo
- Publication number
- ZA200109794B ZA200109794B ZA200109794A ZA200109794A ZA200109794B ZA 200109794 B ZA200109794 B ZA 200109794B ZA 200109794 A ZA200109794 A ZA 200109794A ZA 200109794 A ZA200109794 A ZA 200109794A ZA 200109794 B ZA200109794 B ZA 200109794B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- phenylamino
- benzoic acid
- ethyl
- dichloro
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 128
- 208000037259 Amyloid Plaque Diseases 0.000 title claims description 43
- 102000009091 Amyloidogenic Proteins Human genes 0.000 title claims description 30
- 108010048112 Amyloidogenic Proteins Proteins 0.000 title claims description 30
- 230000002401 inhibitory effect Effects 0.000 title claims description 20
- 238000003384 imaging method Methods 0.000 title claims description 14
- 230000004845 protein aggregation Effects 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 201
- 229910052739 hydrogen Inorganic materials 0.000 claims description 165
- 239000001257 hydrogen Substances 0.000 claims description 153
- 239000005711 Benzoic acid Substances 0.000 claims description 146
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 119
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 106
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 101
- 239000000203 mixture Substances 0.000 claims description 90
- 235000010233 benzoic acid Nutrition 0.000 claims description 81
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 73
- -1 methylene-dioxy Chemical group 0.000 claims description 68
- 238000002360 preparation method Methods 0.000 claims description 65
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 45
- 239000000460 chlorine Substances 0.000 claims description 40
- 239000000126 substance Substances 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 22
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 21
- 239000011737 fluorine Substances 0.000 claims description 21
- 208000024827 Alzheimer disease Diseases 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 230000002776 aggregation Effects 0.000 claims description 17
- 238000004220 aggregation Methods 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000002883 imidazolyl group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 12
- PZTSRWJSPQKOLE-UHFFFAOYSA-N 2-[4-[2-(3,4-dimethylphenyl)ethyl]anilino]-5-nitrobenzoic acid Chemical compound C1=C(C)C(C)=CC=C1CCC(C=C1)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(O)=O PZTSRWJSPQKOLE-UHFFFAOYSA-N 0.000 claims description 11
- WFVPXVOOXSLFGZ-UHFFFAOYSA-N 2-[4-[2-[4-(dibutylamino)phenyl]ethyl]anilino]benzoic acid Chemical compound C1=CC(N(CCCC)CCCC)=CC=C1CCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O WFVPXVOOXSLFGZ-UHFFFAOYSA-N 0.000 claims description 11
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- MHPBLNUMNDIISA-UHFFFAOYSA-N 2-[4-[2-(3,4-dihydroxyphenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(O)C(O)=C1 MHPBLNUMNDIISA-UHFFFAOYSA-N 0.000 claims description 7
- GDQDZEVQJWEDAX-UHFFFAOYSA-N 2-[4-[2-(4-phenoxyphenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC(C=C1)=CC=C1OC1=CC=CC=C1 GDQDZEVQJWEDAX-UHFFFAOYSA-N 0.000 claims description 7
- ITPHQYGXXPWCKV-UHFFFAOYSA-N 2-[4-[4-(3,4-dichlorophenyl)butyl]anilino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC(C=C1)=CC=C1CCCCC1=CC=C(Cl)C(Cl)=C1 ITPHQYGXXPWCKV-UHFFFAOYSA-N 0.000 claims description 7
- WGQXBEBIRLBUKV-UHFFFAOYSA-N 2-[4-[5-(3,4-dichlorophenyl)pentyl]anilino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC(C=C1)=CC=C1CCCCCC1=CC=C(Cl)C(Cl)=C1 WGQXBEBIRLBUKV-UHFFFAOYSA-N 0.000 claims description 7
- UYLHXZKOAHIEQF-UHFFFAOYSA-N 4-(1-thiomorpholin-4-yl-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-yl)morpholine Chemical compound C1CCCC2C1CCNC2(N1CCSCC1)N1CCOCC1 UYLHXZKOAHIEQF-UHFFFAOYSA-N 0.000 claims description 7
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- JGIVSUQXWODQIS-UHFFFAOYSA-N 2-[4-(2-phenylethyl)anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=CC=C1 JGIVSUQXWODQIS-UHFFFAOYSA-N 0.000 claims description 6
- MQKIXQGKIHJOGE-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 MQKIXQGKIHJOGE-UHFFFAOYSA-N 0.000 claims description 6
- SSSLPBTWSJZQAO-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-6-nitrobenzoic acid Chemical compound C1=CC=C([N+]([O-])=O)C(C(=O)O)=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 SSSLPBTWSJZQAO-UHFFFAOYSA-N 0.000 claims description 6
- ZCQOSCDABPVAFB-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 ZCQOSCDABPVAFB-UHFFFAOYSA-N 0.000 claims description 6
- CNASVNVDKYZPEO-UHFFFAOYSA-N 2-[4-[2-(4-pyrrol-1-ylphenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(N2C=CC=C2)C=C1 CNASVNVDKYZPEO-UHFFFAOYSA-N 0.000 claims description 6
- OHGGDIMGQRRMAX-UHFFFAOYSA-N 2-[4-[3-(3,4-dichlorophenyl)propyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCCC1=CC=C(Cl)C(Cl)=C1 OHGGDIMGQRRMAX-UHFFFAOYSA-N 0.000 claims description 6
- CJEIRWQLNMMBHR-UHFFFAOYSA-N 5-nitro-2-[4-(2-phenylethyl)anilino]benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC(C=C1)=CC=C1CCC1=CC=CC=C1 CJEIRWQLNMMBHR-UHFFFAOYSA-N 0.000 claims description 6
- PNZXGBQELZNOKQ-UHFFFAOYSA-N 5-nitro-2-[4-[2-(4-phenylphenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(C=2C=CC=CC=2)C=C1 PNZXGBQELZNOKQ-UHFFFAOYSA-N 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- YMBSYFYVHJEVIQ-UHFFFAOYSA-N 2-[4-(3,4-dichlorophenyl)anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(C=2C=C(Cl)C(Cl)=CC=2)C=C1 YMBSYFYVHJEVIQ-UHFFFAOYSA-N 0.000 claims description 5
- GWKARODGJMADCF-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 GWKARODGJMADCF-UHFFFAOYSA-N 0.000 claims description 5
- ASCDGLGWFVVKPV-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(NC=2C=CC(CCC=3C=C(Cl)C(Cl)=CC=3)=CC=2)=C1 ASCDGLGWFVVKPV-UHFFFAOYSA-N 0.000 claims description 5
- NSCMXISQQMAVCE-UHFFFAOYSA-N 2-[4-[2-(4-phenylmethoxyphenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC(C=C1)=CC=C1OCC1=CC=CC=C1 NSCMXISQQMAVCE-UHFFFAOYSA-N 0.000 claims description 5
- DTOSGALOLCEIRX-UHFFFAOYSA-N 2-[4-[4-(3,4-dichlorophenyl)butyl]anilino]-3,5-dinitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1NC(C=C1)=CC=C1CCCCC1=CC=C(Cl)C(Cl)=C1 DTOSGALOLCEIRX-UHFFFAOYSA-N 0.000 claims description 5
- DUOAHQOVMPWYPR-UHFFFAOYSA-N 2-[4-[4-(3,4-dichlorophenyl)butyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCCCC1=CC=C(Cl)C(Cl)=C1 DUOAHQOVMPWYPR-UHFFFAOYSA-N 0.000 claims description 5
- HOFBDCIYDFDCHW-UHFFFAOYSA-N 2-[4-[(3,4-dichlorophenyl)methyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CC1=CC=C(Cl)C(Cl)=C1 HOFBDCIYDFDCHW-UHFFFAOYSA-N 0.000 claims description 4
- SRRSDBYBJJTGNS-UHFFFAOYSA-N 2-[4-[2-(3,4,5-trihydroxyphenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC(O)=C(O)C(O)=C1 SRRSDBYBJJTGNS-UHFFFAOYSA-N 0.000 claims description 4
- BDKLHMPKCYSDPU-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-3-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(F)(F)F)=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 BDKLHMPKCYSDPU-UHFFFAOYSA-N 0.000 claims description 4
- FVKQVZDNSQWSOK-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 FVKQVZDNSQWSOK-UHFFFAOYSA-N 0.000 claims description 4
- BWXOOVKBHPKGEV-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-5-methylbenzoic acid Chemical compound OC(=O)C1=CC(C)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 BWXOOVKBHPKGEV-UHFFFAOYSA-N 0.000 claims description 4
- LBIJPCUAMWBQOB-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-5-methylsulfonylbenzoic acid Chemical compound OC(=O)C1=CC(S(=O)(=O)C)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 LBIJPCUAMWBQOB-UHFFFAOYSA-N 0.000 claims description 4
- WKMUHXQVZVESBN-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-5-pyrrol-1-ylbenzoic acid Chemical compound OC(=O)C1=CC(N2C=CC=C2)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 WKMUHXQVZVESBN-UHFFFAOYSA-N 0.000 claims description 4
- ZJERLYUQRDVJTG-UHFFFAOYSA-N 2-[4-[2-(3,4-difluorophenyl)ethyl]anilino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(F)C(F)=C1 ZJERLYUQRDVJTG-UHFFFAOYSA-N 0.000 claims description 4
- ZDELDGCLNQHMKZ-UHFFFAOYSA-N 2-[4-[2-[4-(diethylamino)phenyl]ethyl]anilino]benzoic acid Chemical compound C1=CC(N(CC)CC)=CC=C1CCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O ZDELDGCLNQHMKZ-UHFFFAOYSA-N 0.000 claims description 4
- BWZSKFOYMUGUDI-UHFFFAOYSA-N 2-[4-[2-[4-(n-phenylanilino)phenyl]ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(N(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 BWZSKFOYMUGUDI-UHFFFAOYSA-N 0.000 claims description 4
- OUJCOMJAKHYJGQ-UHFFFAOYSA-N 2-[4-[2-[4-[(2-chloro-6-fluorophenyl)methoxy]phenyl]ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC(C=C1)=CC=C1OCC1=C(F)C=CC=C1Cl OUJCOMJAKHYJGQ-UHFFFAOYSA-N 0.000 claims description 4
- ZCMWBUITOPUMIQ-UHFFFAOYSA-N 2-[4-[3-[4-(diethylamino)phenyl]propyl]anilino]benzoic acid Chemical compound C1=CC(N(CC)CC)=CC=C1CCCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O ZCMWBUITOPUMIQ-UHFFFAOYSA-N 0.000 claims description 4
- KZZGAAOVOVAAKL-UHFFFAOYSA-N 4-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]benzene-1,3-dicarboxylic acid Chemical compound OC(=O)C1=CC(C(=O)O)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 KZZGAAOVOVAAKL-UHFFFAOYSA-N 0.000 claims description 4
- MPYQDYTWVYWYED-UHFFFAOYSA-N 5-cyano-2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC(C#N)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 MPYQDYTWVYWYED-UHFFFAOYSA-N 0.000 claims description 4
- PCAOYBFRBVUMRT-UHFFFAOYSA-N 6-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-2,3-difluorobenzoic acid Chemical compound OC(=O)C1=C(F)C(F)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 PCAOYBFRBVUMRT-UHFFFAOYSA-N 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- YWTGQVWIJCBZIP-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-3-methylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 YWTGQVWIJCBZIP-UHFFFAOYSA-N 0.000 claims description 3
- SZKFCYCDIJPCBH-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 SZKFCYCDIJPCBH-UHFFFAOYSA-N 0.000 claims description 3
- MVDMPRPWIYZZMK-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 MVDMPRPWIYZZMK-UHFFFAOYSA-N 0.000 claims description 3
- KTPUSFVOLQLFMY-UHFFFAOYSA-N 2-[4-[2-(3-aminophenyl)ethyl]anilino]benzoic acid Chemical compound NC1=CC=CC(CCC=2C=CC(NC=3C(=CC=CC=3)C(O)=O)=CC=2)=C1 KTPUSFVOLQLFMY-UHFFFAOYSA-N 0.000 claims description 3
- FAYUFDDIFZTIAE-UHFFFAOYSA-N 2-[4-[2-(4-acetamidophenyl)ethyl]anilino]benzoic acid Chemical compound C1=CC(NC(=O)C)=CC=C1CCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O FAYUFDDIFZTIAE-UHFFFAOYSA-N 0.000 claims description 3
- HLKUZYOXDRSGKI-UHFFFAOYSA-N 2-[4-[2-(4-octoxyphenyl)ethyl]anilino]benzoic acid Chemical compound C1=CC(OCCCCCCCC)=CC=C1CCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O HLKUZYOXDRSGKI-UHFFFAOYSA-N 0.000 claims description 3
- UIDDQRNFHBYVHB-UHFFFAOYSA-N 2-[4-[2-(4-octylphenyl)ethyl]anilino]benzoic acid Chemical compound C1=CC(CCCCCCCC)=CC=C1CCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O UIDDQRNFHBYVHB-UHFFFAOYSA-N 0.000 claims description 3
- UWHVNGAIUXGQKA-UHFFFAOYSA-N 2-[4-[2-(4-pyrazol-1-ylphenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(N2N=CC=C2)C=C1 UWHVNGAIUXGQKA-UHFFFAOYSA-N 0.000 claims description 3
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- VHEKRJOGMPFVAW-UHFFFAOYSA-N 2-[4-[5-(3,4-dichlorophenyl)pentyl]anilino]-4-methoxy-5-nitrobenzoic acid Chemical compound C1=C([N+]([O-])=O)C(OC)=CC(NC=2C=CC(CCCCCC=3C=C(Cl)C(Cl)=CC=3)=CC=2)=C1C(O)=O VHEKRJOGMPFVAW-UHFFFAOYSA-N 0.000 claims description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/402—1-aryl substituted, e.g. piretanide
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
- C07C229/58—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position having the nitrogen atom of at least one of the amino groups further bound to a carbon atom of a six-membered aromatic ring, e.g. N-phenyl-anthranilic acids
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/62—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino groups and at least two carboxyl groups bound to carbon atoms of the same six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/64—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by singly-bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/42—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/43—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/51—Y being a hydrogen or a carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
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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
- C07D233/66—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 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
- C07D233/88—Nitrogen atoms, e.g. allantoin
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- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
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- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Medicinal Preparation (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US13855099P | 1999-06-10 | 1999-06-10 |
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ZA200109794A ZA200109794B (en) | 1999-06-10 | 2001-11-28 | Method of inhibiting amyloid protein aggregation and imaging amyloid deposits. |
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EP (1) | EP1225886A2 (ru) |
JP (1) | JP2003504310A (ru) |
KR (1) | KR20020008224A (ru) |
CN (1) | CN1378446A (ru) |
AP (1) | AP2002002387A0 (ru) |
AU (1) | AU775157B2 (ru) |
BG (1) | BG106293A (ru) |
BR (1) | BR0011728A (ru) |
CA (1) | CA2375551A1 (ru) |
CR (1) | CR6528A (ru) |
DZ (1) | DZ3252A1 (ru) |
EA (1) | EA004632B1 (ru) |
EE (1) | EE200100673A (ru) |
GE (1) | GEP20053423B (ru) |
HK (1) | HK1048258A1 (ru) |
HR (1) | HRP20020026A2 (ru) |
HU (1) | HUP0202508A3 (ru) |
IL (1) | IL146971A0 (ru) |
IS (1) | IS6193A (ru) |
MA (1) | MA26805A1 (ru) |
MX (1) | MXPA01012318A (ru) |
NO (1) | NO20015995L (ru) |
NZ (1) | NZ515621A (ru) |
OA (1) | OA11963A (ru) |
PL (1) | PL352430A1 (ru) |
SK (1) | SK17632001A3 (ru) |
TR (1) | TR200103551T2 (ru) |
WO (1) | WO2000076489A2 (ru) |
YU (1) | YU86701A (ru) |
ZA (1) | ZA200109794B (ru) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2001070667A1 (fr) * | 2000-03-22 | 2001-09-27 | Bf Research Institute, Inc. | Sonde de diagnostic par image, a base d'azobenzene substitue ou d'un analogue de celui-ci, pour les maladies imputables a l'accumulation d'amyloide et composition pour le diagnostic par image le contenant |
CA2357450A1 (en) * | 2000-09-29 | 2002-03-29 | Warner-Lambert Company | Phenoxazine analogs useful as amyloid aggregation inhibitors and treatment of alzheimer's disease and disorders related to amyloidosis |
GB0225548D0 (en) | 2002-11-01 | 2002-12-11 | Glaxo Group Ltd | Compounds |
ES2327372B1 (es) * | 2007-04-23 | 2010-08-24 | Laboratorios Almirall S.A. | Nuevos derivados de los acidos amino-nicotinico y amino-isonicotinico. |
ES2319596B1 (es) | 2006-12-22 | 2010-02-08 | Laboratorios Almirall S.A. | Nuevos derivados de los acidos amino-nicotinico y amino-isonicotinico. |
US20100204230A1 (en) | 2007-02-12 | 2010-08-12 | Peter Blurton | Piperazine derivatives for treatment of ad and related conditions |
US20080253967A1 (en) * | 2007-04-13 | 2008-10-16 | Kung Hank F | Halo-Stilbene Derivatives And Their Use For Binding And Imaging Of Amyloid Plaques |
UY31272A1 (es) | 2007-08-10 | 2009-01-30 | Almirall Lab | Nuevos derivados de ácido azabifenilaminobenzoico |
EP2135610A1 (en) | 2008-06-20 | 2009-12-23 | Laboratorios Almirall, S.A. | Combination comprising DHODH inhibitors and methotrexate |
JP2012501344A (ja) * | 2008-08-29 | 2012-01-19 | トレヴェンティス コーポレイション | アミロイド症を治療する組成物及び方法 |
EP2239256A1 (en) | 2009-03-13 | 2010-10-13 | Almirall, S.A. | Sodium salt of 5-cyclopropyl-2-{[2-(2,6-difluorophenyl)pyrimidin-5-yl]amino}benzoic acid as DHODH inhibitor |
EP2228367A1 (en) * | 2009-03-13 | 2010-09-15 | Almirall, S.A. | Addition salts of amines containing hydroxyl and/or carboxylic groups with amino nicotinic acid derivatives as DHODH inhibitors |
EP2314577A1 (en) | 2009-10-16 | 2011-04-27 | Almirall, S.A. | Process for manufacturing 2-[(3,5-difluoro-3'-methoxy-1,1'-biphenyl-4-yl)amino]nicotinic acid |
WO2011101787A1 (en) * | 2010-02-16 | 2011-08-25 | Università Degli Studi Di Siena | Non peptidic 14-3-3 inhibitors and the use thereof |
EP2643303A1 (en) * | 2010-11-24 | 2013-10-02 | Allergan, Inc. | Modulators of s1p receptors |
CN108524482B (zh) * | 2017-03-02 | 2022-11-25 | 中国科学院上海药物研究所 | 2-(取代苯氨基)苯甲酸类fto抑制剂治疗白血病的用途 |
WO2019031472A1 (ja) * | 2017-08-07 | 2019-02-14 | 国立大学法人広島大学 | 新規アントラニル酸系化合物、並びにそれを用いたPin1阻害剤、炎症性疾患の治療剤及び癌の治療剤 |
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US5196444A (en) * | 1990-04-27 | 1993-03-23 | Takeda Chemical Industries, Ltd. | 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate and compositions and methods of pharmaceutical use thereof |
US5739169A (en) * | 1996-05-31 | 1998-04-14 | Procept, Incorporated | Aromatic compounds for inhibiting immune response |
SK17622001A3 (sk) * | 1999-06-10 | 2003-06-03 | Warner-Lambert Company | Izoindolínové deriváty, ich použitie a farmaceutické kompozície na ich báze |
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2000
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- 2000-05-31 SK SK1763-2001A patent/SK17632001A3/sk unknown
- 2000-05-31 PL PL00352430A patent/PL352430A1/xx not_active Application Discontinuation
- 2000-05-31 GE GE4687A patent/GEP20053423B/en unknown
- 2000-05-31 EE EEP200100673A patent/EE200100673A/xx unknown
- 2000-05-31 NZ NZ515621A patent/NZ515621A/en unknown
- 2000-05-31 MX MXPA01012318A patent/MXPA01012318A/es not_active Application Discontinuation
- 2000-05-31 EA EA200101135A patent/EA004632B1/ru not_active IP Right Cessation
- 2000-05-31 WO PCT/US2000/015071 patent/WO2000076489A2/en not_active Application Discontinuation
- 2000-05-31 TR TR2001/03551T patent/TR200103551T2/xx unknown
- 2000-05-31 IL IL14697100A patent/IL146971A0/xx unknown
- 2000-05-31 HU HU0202508A patent/HUP0202508A3/hu unknown
- 2000-05-31 OA OA1200100327A patent/OA11963A/en unknown
- 2000-05-31 KR KR1020017015879A patent/KR20020008224A/ko not_active Application Discontinuation
- 2000-05-31 BR BR0011728-5A patent/BR0011728A/pt not_active IP Right Cessation
- 2000-05-31 AP APAP/P/2002/002387A patent/AP2002002387A0/en unknown
- 2000-05-31 YU YU86701A patent/YU86701A/sh unknown
- 2000-05-31 DZ DZ003252A patent/DZ3252A1/fr active
- 2000-05-31 EP EP00939471A patent/EP1225886A2/en not_active Withdrawn
- 2000-05-31 CN CN00808672A patent/CN1378446A/zh active Pending
- 2000-05-31 CA CA002375551A patent/CA2375551A1/en not_active Abandoned
- 2000-05-31 AU AU54553/00A patent/AU775157B2/en not_active Ceased
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2001
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- 2001-12-07 CR CR6528A patent/CR6528A/es not_active Application Discontinuation
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2002
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- 2002-01-09 BG BG106293A patent/BG106293A/xx unknown
- 2002-01-10 HR HR20020026A patent/HRP20020026A2/hr not_active Application Discontinuation
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2003
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Also Published As
Publication number | Publication date |
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CA2375551A1 (en) | 2000-12-21 |
IL146971A0 (en) | 2002-08-14 |
JP2003504310A (ja) | 2003-02-04 |
KR20020008224A (ko) | 2002-01-29 |
EP1225886A2 (en) | 2002-07-31 |
AU775157B2 (en) | 2004-07-22 |
NO20015995D0 (no) | 2001-12-07 |
MXPA01012318A (es) | 2002-07-22 |
BG106293A (en) | 2002-06-28 |
GEP20053423B (en) | 2005-01-25 |
CN1378446A (zh) | 2002-11-06 |
HUP0202508A2 (hu) | 2002-12-28 |
HRP20020026A2 (en) | 2003-08-31 |
EA200101135A1 (ru) | 2002-06-27 |
NZ515621A (en) | 2004-05-28 |
BR0011728A (pt) | 2002-02-26 |
WO2000076489A3 (en) | 2002-05-30 |
CR6528A (es) | 2004-02-23 |
SK17632001A3 (sk) | 2003-03-04 |
DZ3252A1 (ru) | 2000-12-21 |
IS6193A (is) | 2001-12-07 |
OA11963A (en) | 2006-04-17 |
HK1048258A1 (zh) | 2003-03-28 |
PL352430A1 (en) | 2003-08-25 |
EE200100673A (et) | 2003-02-17 |
YU86701A (sh) | 2004-09-03 |
AU5455300A (en) | 2001-01-02 |
HUP0202508A3 (en) | 2003-03-28 |
AP2002002387A0 (en) | 2002-03-31 |
MA26805A1 (fr) | 2004-12-20 |
NO20015995L (no) | 2002-02-04 |
TR200103551T2 (tr) | 2002-12-23 |
EA004632B1 (ru) | 2004-06-24 |
WO2000076489A2 (en) | 2000-12-21 |
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