JP2003504310A - アミロイドタンパク質凝集阻害方法およびアミロイド沈着物の画像化方法 - Google Patents
アミロイドタンパク質凝集阻害方法およびアミロイド沈着物の画像化方法Info
- Publication number
- JP2003504310A JP2003504310A JP2001502823A JP2001502823A JP2003504310A JP 2003504310 A JP2003504310 A JP 2003504310A JP 2001502823 A JP2001502823 A JP 2001502823A JP 2001502823 A JP2001502823 A JP 2001502823A JP 2003504310 A JP2003504310 A JP 2003504310A
- Authority
- JP
- Japan
- Prior art keywords
- phenylamino
- phenyl
- ethyl
- benzoic acid
- dichloro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 120
- 208000037259 Amyloid Plaque Diseases 0.000 title claims abstract description 40
- 102000009091 Amyloidogenic Proteins Human genes 0.000 title claims abstract description 26
- 108010048112 Amyloidogenic Proteins Proteins 0.000 title claims abstract description 26
- 230000004845 protein aggregation Effects 0.000 title claims abstract description 18
- 238000003384 imaging method Methods 0.000 title claims abstract description 12
- 230000005764 inhibitory process Effects 0.000 title claims description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 225
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 18
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 17
- -1 -CF 3 Chemical group 0.000 claims description 121
- 229910052739 hydrogen Inorganic materials 0.000 claims description 115
- 239000001257 hydrogen Substances 0.000 claims description 115
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 103
- 239000000460 chlorine Substances 0.000 claims description 89
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 74
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 71
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 54
- 239000005711 Benzoic acid Substances 0.000 claims description 41
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 34
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 34
- 239000000126 substance Substances 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 28
- 235000010233 benzoic acid Nutrition 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 19
- 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
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 125000002883 imidazolyl group Chemical group 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 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
- 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 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
- 239000000654 additive Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 13
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 13
- 230000000996 additive effect Effects 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 230000002776 aggregation Effects 0.000 claims description 10
- 238000004220 aggregation Methods 0.000 claims description 10
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 10
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 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 9
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 9
- 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 8
- 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 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
- 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 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
- 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
- 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
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 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
- 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 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
- 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 7
- 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 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
- 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
- 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 7
- 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 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
- 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
- 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
- COJWXGVEMDSDRP-UHFFFAOYSA-N 2-[4-[2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]ethyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCC(C=C1)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 COJWXGVEMDSDRP-UHFFFAOYSA-N 0.000 claims description 6
- LWEWSOVHBLBXOH-UHFFFAOYSA-N 2-[4-[2-[4-[3-(dimethylamino)propoxy]phenyl]ethyl]anilino]benzoic acid Chemical compound C1=CC(OCCCN(C)C)=CC=C1CCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O LWEWSOVHBLBXOH-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 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 6
- 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 6
- 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 6
- 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 6
- 239000002253 acid Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 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 5
- JSYJOCYGORZKEJ-UHFFFAOYSA-N 2-[4-[3-(4-nitrophenyl)propyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCCC1=CC=C([N+]([O-])=O)C=C1 JSYJOCYGORZKEJ-UHFFFAOYSA-N 0.000 claims description 5
- BMSPAFDAZFNJBZ-UHFFFAOYSA-N 2-[4-[3-[4-(ethylamino)phenyl]propyl]anilino]benzoic acid Chemical compound C1=CC(NCC)=CC=C1CCCC(C=C1)=CC=C1NC1=CC=CC=C1C(O)=O BMSPAFDAZFNJBZ-UHFFFAOYSA-N 0.000 claims description 5
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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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- 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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- 229910052708 sodium Inorganic materials 0.000 description 1
- 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
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- 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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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
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- 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
- 210000001685 thyroid gland Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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- 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
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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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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
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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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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 |
ES2319596B1 (es) * | 2006-12-22 | 2010-02-08 | Laboratorios Almirall S.A. | Nuevos derivados de los acidos amino-nicotinico y amino-isonicotinico. |
ES2327372B1 (es) * | 2007-04-23 | 2010-08-24 | Laboratorios Almirall S.A. | Nuevos derivados de los acidos amino-nicotinico y amino-isonicotinico. |
CA2676715A1 (en) | 2007-02-12 | 2008-08-21 | Merck & Co., Inc. | 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 |
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 |
EP2536405A1 (en) * | 2010-02-16 | 2012-12-26 | Universita Degli Studi di Siena | Non peptidic 14-3-3 inhibitors and the use thereof |
WO2012071186A1 (en) * | 2010-11-24 | 2012-05-31 | Allergan, Inc. | Modulators of s1p receptors |
JP7046968B2 (ja) * | 2017-03-02 | 2022-04-04 | 上海 インスティテュート オブ マテリア メディカ、チャイニーズ アカデミー オブ サイエンシーズ | 2-(置換フェニルヘテロ)芳香族カルボン酸系fto阻害剤、その製造方法およびその使用 |
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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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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
JPWO2019031472A1 (ja) * | 2017-08-07 | 2020-12-03 | 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 |
JP7205830B2 (ja) | 2017-08-07 | 2023-01-17 | 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 |
US12357626B2 (en) | 2017-08-07 | 2025-07-15 | Amenis Bioscience, Inc. | Anthranilic acid-based compound, and Pin1 inhibitor, therapeutic agent for inflammatory diseases and therapeutic agent for cancer that use the same |
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