HRP20020026A2 - 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
- HRP20020026A2 HRP20020026A2 HR20020026A HRP20020026A HRP20020026A2 HR P20020026 A2 HRP20020026 A2 HR P20020026A2 HR 20020026 A HR20020026 A HR 20020026A HR P20020026 A HRP20020026 A HR P20020026A HR P20020026 A2 HRP20020026 A2 HR P20020026A2
- Authority
- HR
- Croatia
- Prior art keywords
- phenylamino
- ethyl
- acid
- dichlorophenyl
- benzoic acid
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 127
- 208000037259 Amyloid Plaque Diseases 0.000 title claims description 40
- 102000009091 Amyloidogenic Proteins Human genes 0.000 title claims description 27
- 108010048112 Amyloidogenic Proteins Proteins 0.000 title claims description 27
- 230000002401 inhibitory effect Effects 0.000 title description 7
- 230000004845 protein aggregation Effects 0.000 title description 7
- 238000003384 imaging method Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 218
- 229910052739 hydrogen Inorganic materials 0.000 claims description 110
- 239000001257 hydrogen Substances 0.000 claims description 110
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 84
- -1 -CO2C1-C6 alkyl Chemical group 0.000 claims description 81
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 76
- 239000000460 chlorine Substances 0.000 claims description 48
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 33
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 24
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 230000002776 aggregation Effects 0.000 claims description 21
- 238000004220 aggregation Methods 0.000 claims description 21
- 230000015572 biosynthetic process Effects 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 208000024827 Alzheimer disease Diseases 0.000 claims description 18
- 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 17
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 17
- 239000011737 fluorine Substances 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- DKXYNAFWDNXYCZ-UHFFFAOYSA-N 2-[4-[2-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(C(F)(F)F)=C1 DKXYNAFWDNXYCZ-UHFFFAOYSA-N 0.000 claims description 15
- 125000002883 imidazolyl group Chemical group 0.000 claims description 15
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 15
- BJZITOOHORBKQU-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC(C(F)(F)F)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 BJZITOOHORBKQU-UHFFFAOYSA-N 0.000 claims description 14
- 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 14
- 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 14
- 239000011230 binding agent Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 12
- 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 11
- 235000010233 benzoic acid Nutrition 0.000 claims description 11
- 238000001514 detection method Methods 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 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 9
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 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 8
- 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 8
- FMUXMGOMUFSCOU-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-6-(trifluoromethyl)benzoic acid Chemical compound C1=CC=C(C(F)(F)F)C(C(=O)O)=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 FMUXMGOMUFSCOU-UHFFFAOYSA-N 0.000 claims description 8
- 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 8
- 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 8
- 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 8
- OINYTMCUXWLARG-UHFFFAOYSA-N 2-[4-[3-(4-aminophenyl)propyl]anilino]benzoic acid Chemical compound C1=CC(N)=CC=C1CCCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O OINYTMCUXWLARG-UHFFFAOYSA-N 0.000 claims description 8
- 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 8
- 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 8
- 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 8
- JRFAKTZTBXPSEJ-UHFFFAOYSA-N 5-amino-2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC(N)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 JRFAKTZTBXPSEJ-UHFFFAOYSA-N 0.000 claims description 8
- 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 8
- 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 8
- 239000005711 Benzoic acid Substances 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 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 7
- 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 7
- 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 7
- 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
- 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 7
- 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 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
- 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
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 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 6
- RMDRQQNMYPTLNB-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-3,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(F)=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 RMDRQQNMYPTLNB-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 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 6
- PCQVMCCFNJATOU-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-4,6-difluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=C(F)C=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 PCQVMCCFNJATOU-UHFFFAOYSA-N 0.000 claims description 6
- XDILPRILIALQMZ-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 XDILPRILIALQMZ-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- BYPCDMSWQJNAAK-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-5-imidazol-1-ylbenzoic acid Chemical compound OC(=O)C1=CC(N2C=NC=C2)=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 BYPCDMSWQJNAAK-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 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 6
- VSNIZJPNLXRWGM-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]-6-fluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 VSNIZJPNLXRWGM-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
- 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 6
- 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 6
- 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 6
- 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 6
- 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 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
- ZVRPHQACWPRDTR-UHFFFAOYSA-N 2-[4-[2-[3-(3,5-dichlorophenoxy)phenyl]ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=CC(OC=2C=C(Cl)C=C(Cl)C=2)=C1 ZVRPHQACWPRDTR-UHFFFAOYSA-N 0.000 claims description 6
- CWRHCMVLQFWVFX-UHFFFAOYSA-N 2-[4-[2-[4-(1,3-diethoxypropan-2-yl)phenyl]ethyl]anilino]benzoic acid Chemical compound C1=CC(C(COCC)COCC)=CC=C1CCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O CWRHCMVLQFWVFX-UHFFFAOYSA-N 0.000 claims description 6
- MURZLDHUURDCGT-UHFFFAOYSA-N 2-[4-[2-[4-(2-phenylethenyl)phenyl]ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC(C=C1)=CC=C1C=CC1=CC=CC=C1 MURZLDHUURDCGT-UHFFFAOYSA-N 0.000 claims description 6
- YBRRAPJWHURFQS-UHFFFAOYSA-N 2-[4-[2-[4-(4-ethylphenyl)phenyl]ethyl]anilino]benzoic acid Chemical compound C1=CC(CC)=CC=C1C(C=C1)=CC=C1CCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O YBRRAPJWHURFQS-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 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 6
- 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 6
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- JHMNGIIQZJTKAG-UHFFFAOYSA-N methyl 2-[4-[3-(3,4-dichlorophenyl)propyl]anilino]-5-nitrobenzoate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=CC=C1NC(C=C1)=CC=C1CCCC1=CC=C(Cl)C(Cl)=C1 JHMNGIIQZJTKAG-UHFFFAOYSA-N 0.000 description 1
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- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
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- XXPOAKFSALGXEU-UHFFFAOYSA-M potassium 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 XXPOAKFSALGXEU-UHFFFAOYSA-M 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
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- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
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- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
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- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
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- 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 1
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- WXQVQXSIOBONMH-UHFFFAOYSA-M sodium 2-[4-[2-(3,4-dichlorophenyl)ethyl]anilino]benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC1=CC=C(Cl)C(Cl)=C1 WXQVQXSIOBONMH-UHFFFAOYSA-M 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- CIJQGPVMMRXSQW-UHFFFAOYSA-M sodium;2-aminoacetic acid;hydroxide Chemical compound O.[Na+].NCC([O-])=O CIJQGPVMMRXSQW-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
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- 125000005504 styryl group Chemical group 0.000 description 1
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- 150000003900 succinic acid esters Chemical class 0.000 description 1
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- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
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- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
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- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
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- 235000020357 syrup Nutrition 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
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- 125000005490 tosylate group Chemical group 0.000 description 1
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- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
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- 239000000080 wetting agent Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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- 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
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- 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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- 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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- 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
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- 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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- 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
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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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- 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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- Pharmacology & Pharmacy (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (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)
- Pyridine Compounds (AREA)
- Medicinal Preparation (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
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US13855099P | 1999-06-10 | 1999-06-10 | |
PCT/US2000/015071 WO2000076489A2 (en) | 1999-06-10 | 2000-05-31 | Method of inhibiting amyloid protein aggregation and imaging amyloid deposits |
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KR (1) | KR20020008224A (hu) |
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US20030138374A1 (en) * | 2000-03-22 | 2003-07-24 | Yukitsuda Kudo | Image diagnosis probe based on substituted azobenzene or analogue thereof for disease attributable to amyloid accumulation and composition for image diagnosis containing the same |
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. |
JP2010518064A (ja) | 2007-02-12 | 2010-05-27 | メルク・シャープ・エンド・ドーム・コーポレイション | Adおよび関連状態の治療のためのピペラジン誘導体 |
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 |
EP2320897B1 (en) * | 2008-08-29 | 2014-01-15 | Treventis Corporation | Compositions and methods of treating amyloid disease |
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 |
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 |
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 |
JP2014504280A (ja) * | 2010-11-24 | 2014-02-20 | アラーガン インコーポレイテッド | S1p受容体調節剤 |
WO2018157842A1 (zh) * | 2017-03-02 | 2018-09-07 | 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 |
KR20200042906A (ko) * | 2017-08-07 | 2020-04-24 | 고쿠리츠다이가쿠호진 히로시마다이가쿠 | 신규 안트라닐산계 화합물, 및 이것을 사용한 Pin1 저해제, 염증성 질환의 치료제 및 암의 치료제 |
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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 |
ES2223531T3 (es) * | 1999-06-10 | 2005-03-01 | Warner-Lambert Company Llc | Metodo de inhibir la agregacion de proteinas amiloides y de formacion de imagenes de depositos amiloides usando derivados de isoindolina. |
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SK17632001A3 (sk) | 2003-03-04 |
AU775157B2 (en) | 2004-07-22 |
DZ3252A1 (hu) | 2000-12-21 |
PL352430A1 (en) | 2003-08-25 |
ZA200109794B (en) | 2003-07-01 |
MA26805A1 (fr) | 2004-12-20 |
AP2002002387A0 (en) | 2002-03-31 |
HUP0202508A2 (hu) | 2002-12-28 |
CN1378446A (zh) | 2002-11-06 |
AU5455300A (en) | 2001-01-02 |
GEP20053423B (en) | 2005-01-25 |
EE200100673A (et) | 2003-02-17 |
EP1225886A2 (en) | 2002-07-31 |
BR0011728A (pt) | 2002-02-26 |
BG106293A (en) | 2002-06-28 |
IL146971A0 (en) | 2002-08-14 |
HUP0202508A3 (en) | 2003-03-28 |
EA004632B1 (ru) | 2004-06-24 |
YU86701A (sh) | 2004-09-03 |
NO20015995D0 (no) | 2001-12-07 |
MXPA01012318A (es) | 2002-07-22 |
OA11963A (en) | 2006-04-17 |
TR200103551T2 (tr) | 2002-12-23 |
JP2003504310A (ja) | 2003-02-04 |
WO2000076489A2 (en) | 2000-12-21 |
CA2375551A1 (en) | 2000-12-21 |
IS6193A (is) | 2001-12-07 |
WO2000076489A3 (en) | 2002-05-30 |
KR20020008224A (ko) | 2002-01-29 |
CR6528A (es) | 2004-02-23 |
NO20015995L (no) | 2002-02-04 |
HK1048258A1 (zh) | 2003-03-28 |
NZ515621A (en) | 2004-05-28 |
EA200101135A1 (ru) | 2002-06-27 |
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