CA2732280A1 - Benzoimidazole derivatives and glycogen synthase kinase-3 beta inhibitors containing the same - Google Patents
Benzoimidazole derivatives and glycogen synthase kinase-3 beta inhibitors containing the same Download PDFInfo
- Publication number
- CA2732280A1 CA2732280A1 CA2732280A CA2732280A CA2732280A1 CA 2732280 A1 CA2732280 A1 CA 2732280A1 CA 2732280 A CA2732280 A CA 2732280A CA 2732280 A CA2732280 A CA 2732280A CA 2732280 A1 CA2732280 A1 CA 2732280A1
- Authority
- CA
- Canada
- Prior art keywords
- benzo
- imidazole
- hydroxy
- thiophen
- carboxamide
- 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.)
- Abandoned
Links
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 title claims abstract description 21
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 title claims abstract description 21
- 239000003112 inhibitor Substances 0.000 title claims abstract description 10
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical class C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 123
- 238000000034 method Methods 0.000 claims description 108
- -1 p-toluenesulfonylamino Chemical group 0.000 claims description 104
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 59
- ZBNZAJFNDPPMDT-UHFFFAOYSA-N 1h-imidazole-5-carboxamide Chemical compound NC(=O)C1=CNC=N1 ZBNZAJFNDPPMDT-UHFFFAOYSA-N 0.000 claims description 54
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 239000012453 solvate Substances 0.000 claims description 28
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 150000001408 amides Chemical class 0.000 claims description 18
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 18
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 14
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 10
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 7
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- UVKHHBRUBXLKTP-QPJJXVBHSA-N (e)-3-(1h-imidazol-5-yl)-n-(7-methoxy-2-thiophen-2-yl-1h-benzimidazol-4-yl)prop-2-enamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1NC(=O)\C=C\C1=CN=CN1 UVKHHBRUBXLKTP-QPJJXVBHSA-N 0.000 claims description 5
- KMTNZCAGMPTVOX-UHFFFAOYSA-N 7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxylic acid Chemical compound N1C=2C(C(=O)O)=CC=C(O)C=2N=C1C1=CC=CS1 KMTNZCAGMPTVOX-UHFFFAOYSA-N 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 5
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 4
- 206010026749 Mania Diseases 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 150000001409 amidines Chemical class 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- MZHSZYCOVLPFLX-UHFFFAOYSA-N 1-(2-cyclopropyl-7-hydroxy-1h-benzimidazol-4-yl)-3-(4-hydroxyphenyl)urea Chemical compound C1=CC(O)=CC=C1NC(=O)NC1=CC=C(O)C2=C1N=C(C1CC1)N2 MZHSZYCOVLPFLX-UHFFFAOYSA-N 0.000 claims description 3
- HVIMPUISPMUNPS-UHFFFAOYSA-N 2-cyclopropyl-7-hydroxy-n-[2-(4-sulfamoylphenyl)ethyl]-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)C1=CC=C(O)C2=C1NC(C1CC1)=N2 HVIMPUISPMUNPS-UHFFFAOYSA-N 0.000 claims description 3
- BBIVHOWFUCOWKO-UHFFFAOYSA-N 7-hydroxy-n-[2-(4-nitrophenoxy)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCOC1=CC=C([N+]([O-])=O)C=C1 BBIVHOWFUCOWKO-UHFFFAOYSA-N 0.000 claims description 3
- GOPDFXUMARJJEA-UHFFFAOYSA-N amino(nitro)azanide Chemical compound N[N-][N+]([O-])=O GOPDFXUMARJJEA-UHFFFAOYSA-N 0.000 claims description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- TWGFJXFYAIVMSD-LBPRGKRZSA-N methyl (2s)-2-[(7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carbonyl)amino]-3-(1h-imidazol-5-yl)propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C=1C=2N=C(NC=2C(O)=CC=1)C=1SC=CC=1)C1=CN=CN1 TWGFJXFYAIVMSD-LBPRGKRZSA-N 0.000 claims description 3
- UQBQUPKEQYLNEP-KRWDZBQOSA-N methyl (2s)-2-[(7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carbonyl)amino]-3-(1h-indol-3-yl)propanoate Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)OC)C(=O)C(C=1N=2)=CC=C(O)C=1NC=2C1=CC=CS1 UQBQUPKEQYLNEP-KRWDZBQOSA-N 0.000 claims description 3
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 3
- VSWOMRSVSRDHTQ-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N=1C=2C(C(=O)NCCN(C)C)=CC=C(O)C=2NC=1C1=CC=CS1 VSWOMRSVSRDHTQ-UHFFFAOYSA-N 0.000 claims description 3
- HCDYZIZXEZAMPG-UHFFFAOYSA-N n-[5-hydroxy-2-(piperidin-3-ylcarbamoyl)phenyl]thiophene-2-carboxamide Chemical compound C=1C=CSC=1C(=O)NC1=CC(O)=CC=C1C(=O)NC1CCCNC1 HCDYZIZXEZAMPG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- ZUVFATUZMPMHOH-NSHDSACASA-N (2s)-2-[(7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carbonyl)amino]-3-(1h-imidazol-5-yl)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=2N=C(NC=2C(O)=CC=1)C=1SC=CC=1)C1=CN=CN1 ZUVFATUZMPMHOH-NSHDSACASA-N 0.000 claims description 2
- MUVKYWUUGPEPCZ-INIZCTEOSA-N (2s)-2-[(7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carbonyl)amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(C=1N=2)=CC=C(O)C=1NC=2C1=CC=CS1 MUVKYWUUGPEPCZ-INIZCTEOSA-N 0.000 claims description 2
- WEPGUFPFXZWBCK-UHFFFAOYSA-N 2-(furan-2-yl)-7-hydroxy-n-(1,3-thiazol-2-yl)-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3OC=CC=3)NC=2C(O)=CC=C1C(=O)NC1=NC=CS1 WEPGUFPFXZWBCK-UHFFFAOYSA-N 0.000 claims description 2
- SBZNOMSJFLVNDA-UHFFFAOYSA-N 2-(furan-2-yl)-7-hydroxy-n-(2-phenylethyl)-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3OC=CC=3)NC=2C(O)=CC=C1C(=O)NCCC1=CC=CC=C1 SBZNOMSJFLVNDA-UHFFFAOYSA-N 0.000 claims description 2
- SKWUVECPMONQGU-UHFFFAOYSA-N 2-(furan-2-yl)-7-hydroxy-n-phenyl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3OC=CC=3)NC=2C(O)=CC=C1C(=O)NC1=CC=CC=C1 SKWUVECPMONQGU-UHFFFAOYSA-N 0.000 claims description 2
- CUPJXQFPTJBZOZ-UHFFFAOYSA-N 2-cyclopentyl-7-hydroxy-n-[2-(4-hydroxyphenyl)ethyl]-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(O)=CC=C1CCNC(=O)C1=CC=C(O)C2=C1NC(C1CCCC1)=N2 CUPJXQFPTJBZOZ-UHFFFAOYSA-N 0.000 claims description 2
- MXQIXJJYQFBVJN-UHFFFAOYSA-N 2-cyclopropyl-n-(2,3-dihydroxypropyl)-7-hydroxy-1h-benzimidazole-4-carboxamide Chemical compound N1C=2C(C(=O)NCC(O)CO)=CC=C(O)C=2N=C1C1CC1 MXQIXJJYQFBVJN-UHFFFAOYSA-N 0.000 claims description 2
- HHGDSAWNMROJTC-UHFFFAOYSA-N 2-cyclopropyl-n-[2-(4-fluorophenyl)ethyl]-7-hydroxy-1h-benzimidazole-4-carboxamide Chemical compound C1=2NC(C3CC3)=NC=2C(O)=CC=C1C(=O)NCCC1=CC=C(F)C=C1 HHGDSAWNMROJTC-UHFFFAOYSA-N 0.000 claims description 2
- KSMCYMNDVNDOEW-UHFFFAOYSA-N 7-fluoro-n-[2-(1h-imidazol-5-yl)ethyl]-2-thiophen-2-yl-3h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(F)=CC=C1C(=O)NCCC1=CN=CN1 KSMCYMNDVNDOEW-UHFFFAOYSA-N 0.000 claims description 2
- VLBUEFFYBHGVQX-UHFFFAOYSA-N 7-hydroxy-2-phenyl-n-(2-phenylethyl)-1h-benzimidazole-4-carboxamide Chemical compound C1=2NC(C=3C=CC=CC=3)=NC=2C(O)=CC=C1C(=O)NCCC1=CC=CC=C1 VLBUEFFYBHGVQX-UHFFFAOYSA-N 0.000 claims description 2
- JPQBWJWUGVSDBA-UHFFFAOYSA-N 7-hydroxy-2-thiophen-2-yl-3h-benzimidazole-5-carboxamide Chemical compound N=1C2=CC(C(=O)N)=CC(O)=C2NC=1C1=CC=CS1 JPQBWJWUGVSDBA-UHFFFAOYSA-N 0.000 claims description 2
- NZBRUYFITVWYNU-UHFFFAOYSA-N 7-hydroxy-2-thiophen-2-yl-n-(2-thiophen-2-ylethyl)-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCC1=CC=CS1 NZBRUYFITVWYNU-UHFFFAOYSA-N 0.000 claims description 2
- BMDGRFFORKPVDW-UHFFFAOYSA-N 7-hydroxy-n-(1,3-thiazol-2-yl)-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NC1=NC=CS1 BMDGRFFORKPVDW-UHFFFAOYSA-N 0.000 claims description 2
- RQWPXWYHCDTLCQ-UHFFFAOYSA-N 7-hydroxy-n-(3-imidazol-1-ylpropyl)-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCCN1C=CN=C1 RQWPXWYHCDTLCQ-UHFFFAOYSA-N 0.000 claims description 2
- AOUOLQCMFOELTQ-CYBMUJFWSA-N 7-hydroxy-n-[(2s)-1-hydroxy-3,3-dimethylbutan-2-yl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N=1C=2C(C(=O)N[C@H](CO)C(C)(C)C)=CC=C(O)C=2NC=1C1=CC=CS1 AOUOLQCMFOELTQ-CYBMUJFWSA-N 0.000 claims description 2
- KPMGOOQJFZUQKN-UHFFFAOYSA-N 7-hydroxy-n-[(4-sulfamoylphenyl)methyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 KPMGOOQJFZUQKN-UHFFFAOYSA-N 0.000 claims description 2
- BTRMVOSUMNXHFE-UHFFFAOYSA-N 7-hydroxy-n-[2-(1h-imidazol-2-yl)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCC1=NC=CN1 BTRMVOSUMNXHFE-UHFFFAOYSA-N 0.000 claims description 2
- KIBQEHLLMWSGFX-UHFFFAOYSA-N 7-hydroxy-n-[2-(1h-imidazol-5-yl)ethyl]-1h-indole-3-carboxamide Chemical compound C=1NC=2C(O)=CC=CC=2C=1C(=O)NCCC1=CN=CN1 KIBQEHLLMWSGFX-UHFFFAOYSA-N 0.000 claims description 2
- UHNVSGAVJLZCOT-UHFFFAOYSA-N 7-hydroxy-n-[2-(1h-imidazol-5-yl)ethyl]-2-thiophen-2-yl-3h-benzimidazole-5-carboxamide Chemical compound N1C=2C(O)=CC(C(=O)NCCC=3NC=NC=3)=CC=2N=C1C1=CC=CS1 UHNVSGAVJLZCOT-UHFFFAOYSA-N 0.000 claims description 2
- MROBEFRBDYTTSK-UHFFFAOYSA-N 7-hydroxy-n-[2-(4-hydroxyphenyl)ethyl]-2-phenyl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(O)=CC=C1CCNC(=O)C1=CC=C(O)C2=C1NC(C=1C=CC=CC=1)=N2 MROBEFRBDYTTSK-UHFFFAOYSA-N 0.000 claims description 2
- FLPCFXRGUFUVHJ-UHFFFAOYSA-N 7-hydroxy-n-[2-(4-sulfamoylphenyl)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 FLPCFXRGUFUVHJ-UHFFFAOYSA-N 0.000 claims description 2
- FUGLJOSMSYGJAU-UHFFFAOYSA-N 7-hydroxy-n-[2-(pyridin-4-ylsulfonylamino)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCNS(=O)(=O)C1=CC=NC=C1 FUGLJOSMSYGJAU-UHFFFAOYSA-N 0.000 claims description 2
- LOVNJIKQQJSSDK-UHFFFAOYSA-N 7-hydroxy-n-[3-(2-hydroxyethylamino)propyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N=1C=2C(C(=O)NCCCNCCO)=CC=C(O)C=2NC=1C1=CC=CS1 LOVNJIKQQJSSDK-UHFFFAOYSA-N 0.000 claims description 2
- QJHCQFHTMOZFOW-UHFFFAOYSA-N 7-hydroxy-n-[3-(propan-2-ylamino)propyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N=1C=2C(C(=O)NCCCNC(C)C)=CC=C(O)C=2NC=1C1=CC=CS1 QJHCQFHTMOZFOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 2
- NCFOCOFBHNWJDC-UHFFFAOYSA-N methyl 3-hydroxy-2-[(7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carbonyl)amino]propanoate Chemical compound N=1C=2C(C(=O)NC(CO)C(=O)OC)=CC=C(O)C=2NC=1C1=CC=CS1 NCFOCOFBHNWJDC-UHFFFAOYSA-N 0.000 claims description 2
- HZQOAXBFUCEICD-UHFFFAOYSA-N n-(2-acetamidoethyl)-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N=1C=2C(C(=O)NCCNC(=O)C)=CC=C(O)C=2NC=1C1=CC=CS1 HZQOAXBFUCEICD-UHFFFAOYSA-N 0.000 claims description 2
- COKWCLRPCPQRHW-UHFFFAOYSA-N n-(2-cyclopropyl-7-hydroxy-1h-benzimidazol-4-yl)-2-(4-hydroxyphenyl)acetamide Chemical compound C1=CC(O)=CC=C1CC(=O)NC1=CC=C(O)C2=C1N=C(C1CC1)N2 COKWCLRPCPQRHW-UHFFFAOYSA-N 0.000 claims description 2
- MVIYVSVLUFCKPM-UHFFFAOYSA-N n-(7-hydroxy-2-thiophen-2-yl-1h-benzimidazol-4-yl)-3-(1h-imidazol-5-yl)propanamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1NC(=O)CCC1=CN=CN1 MVIYVSVLUFCKPM-UHFFFAOYSA-N 0.000 claims description 2
- KAXYSAVZDDUQAY-UHFFFAOYSA-N n-[(2,4-difluorophenyl)methyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCC1=CC=C(F)C=C1F KAXYSAVZDDUQAY-UHFFFAOYSA-N 0.000 claims description 2
- CYEZNUPYHKNUEM-UHFFFAOYSA-N n-[2-(4-aminophenyl)ethyl]-2-cyclopentyl-7-hydroxy-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(N)=CC=C1CCNC(=O)C1=CC=C(O)C2=C1NC(C1CCCC1)=N2 CYEZNUPYHKNUEM-UHFFFAOYSA-N 0.000 claims description 2
- QSMNQEMSVXJRQS-UHFFFAOYSA-N n-[2-(4-aminophenyl)ethyl]-7-hydroxy-2-phenyl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(N)=CC=C1CCNC(=O)C1=CC=C(O)C2=C1NC(C=1C=CC=CC=1)=N2 QSMNQEMSVXJRQS-UHFFFAOYSA-N 0.000 claims description 2
- VDMPWEXEHQWQKM-UHFFFAOYSA-N n-[2-(4-fluorophenyl)ethyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCC1=CC=C(F)C=C1 VDMPWEXEHQWQKM-UHFFFAOYSA-N 0.000 claims description 2
- BDRBZSPAJPBMKA-UHFFFAOYSA-N n-[2-(5-carbamoylpyridin-2-yl)oxyethyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1OCCNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 BDRBZSPAJPBMKA-UHFFFAOYSA-N 0.000 claims description 2
- PNYYRFDFEXVEPN-UHFFFAOYSA-N n-[2-(benzenesulfonamido)ethyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCNS(=O)(=O)C1=CC=CC=C1 PNYYRFDFEXVEPN-UHFFFAOYSA-N 0.000 claims description 2
- NGQAEUFCTRTCCT-UHFFFAOYSA-N n-[2-[(5-acetamidopyridin-2-yl)amino]ethyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N1=CC(NC(=O)C)=CC=C1NCCNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 NGQAEUFCTRTCCT-UHFFFAOYSA-N 0.000 claims description 2
- DWOUPRLHBBTUHD-UHFFFAOYSA-N n-[2-hydroxy-5-[2-(1h-imidazol-5-yl)ethylcarbamoyl]phenyl]thiophene-2-carboxamide Chemical compound OC1=CC=C(C(=O)NCCC=2NC=NC=2)C=C1NC(=O)C1=CC=CS1 DWOUPRLHBBTUHD-UHFFFAOYSA-N 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims 10
- 229910052717 sulfur Inorganic materials 0.000 claims 10
- 230000008878 coupling Effects 0.000 claims 7
- 238000010168 coupling process Methods 0.000 claims 7
- 238000005859 coupling reaction Methods 0.000 claims 7
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 3
- 150000001448 anilines Chemical class 0.000 claims 2
- 150000001556 benzimidazoles Chemical class 0.000 claims 2
- 230000003301 hydrolyzing effect Effects 0.000 claims 2
- ODQBWZNQIHEVET-UHFFFAOYSA-N 2-(furan-2-yl)-7-hydroxy-n-[2-[[5-[(4-methylphenyl)sulfonylamino]pyridin-2-yl]amino]ethyl]-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(C=N1)=CC=C1NCCNC(=O)C1=CC=C(O)C2=C1N=C(C=1OC=CC=1)N2 ODQBWZNQIHEVET-UHFFFAOYSA-N 0.000 claims 1
- XUYLZESPGHLNED-LLVKDONJSA-N 7-hydroxy-n-[(2r)-1-hydroxy-3-(1h-imidazol-5-yl)propan-2-yl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C([C@H](CO)NC(=O)C=1C=2N=C(NC=2C(O)=CC=1)C=1SC=CC=1)C1=CNC=N1 XUYLZESPGHLNED-LLVKDONJSA-N 0.000 claims 1
- BSGKOICCPIZSNX-UHFFFAOYSA-N 7-hydroxy-n-[2-(pyridin-2-ylamino)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCNC1=CC=CC=N1 BSGKOICCPIZSNX-UHFFFAOYSA-N 0.000 claims 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 claims 1
- 150000002475 indoles Chemical class 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 239000000047 product Substances 0.000 description 160
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 139
- 239000007787 solid Substances 0.000 description 139
- 239000011541 reaction mixture Substances 0.000 description 131
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 110
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 91
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 88
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
- 238000004128 high performance liquid chromatography Methods 0.000 description 60
- 238000005481 NMR spectroscopy Methods 0.000 description 58
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 53
- 239000000243 solution Substances 0.000 description 51
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- PZXAAFAJWASTJT-UHFFFAOYSA-N 7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxylic acid Chemical compound N=1C=2C(OC)=CC=C(C(O)=O)C=2NC=1C1=CC=CS1 PZXAAFAJWASTJT-UHFFFAOYSA-N 0.000 description 35
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
- 230000015572 biosynthetic process Effects 0.000 description 33
- 238000003786 synthesis reaction Methods 0.000 description 33
- 239000000377 silicon dioxide Substances 0.000 description 27
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 24
- 235000017557 sodium bicarbonate Nutrition 0.000 description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 229910052740 iodine Inorganic materials 0.000 description 23
- 239000007821 HATU Substances 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 239000007832 Na2SO4 Substances 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 14
- 238000002953 preparative HPLC Methods 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- 238000005342 ion exchange Methods 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
- 150000004677 hydrates Chemical class 0.000 description 12
- 230000026731 phosphorylation Effects 0.000 description 12
- 238000006366 phosphorylation reaction Methods 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 10
- 229910015845 BBr3 Inorganic materials 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 7
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- 229940086542 triethylamine Drugs 0.000 description 7
- QCQAZAFKSFCSIP-UHFFFAOYSA-N 2-(furan-2-yl)-7-hydroxy-1h-benzimidazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=C(O)C=2NC=1C1=CC=CO1 QCQAZAFKSFCSIP-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- VMKKFYFBTBSQCI-UHFFFAOYSA-N 2-(furan-2-yl)-7-methoxy-1h-benzimidazole-4-carboxylic acid Chemical compound N1C=2C(OC)=CC=C(C(O)=O)C=2N=C1C1=CC=CO1 VMKKFYFBTBSQCI-UHFFFAOYSA-N 0.000 description 5
- ZXTKGGYXRGFGQZ-UHFFFAOYSA-N 2-cyclopropyl-7-methoxy-1h-benzimidazole-4-carboxylic acid Chemical compound N=1C=2C(OC)=CC=C(C(O)=O)C=2NC=1C1CC1 ZXTKGGYXRGFGQZ-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 229960000956 coumarin Drugs 0.000 description 5
- 235000001671 coumarin Nutrition 0.000 description 5
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- QVDWKLDUBSJEOG-UHFFFAOYSA-N methyl 3-amino-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(N)=C1 QVDWKLDUBSJEOG-UHFFFAOYSA-N 0.000 description 5
- ANXCBFTZWJXBSY-UHFFFAOYSA-N 2-cyclopropyl-7-hydroxy-1h-benzimidazole-4-carboxylic acid Chemical compound N1C=2C(C(=O)O)=CC=C(O)C=2N=C1C1CC1 ANXCBFTZWJXBSY-UHFFFAOYSA-N 0.000 description 4
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- SJZOWOQBEAFCJP-UHFFFAOYSA-N 7-hydroxy-2-phenyl-1h-benzimidazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=C(O)C=2NC=1C1=CC=CC=C1 SJZOWOQBEAFCJP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- OVWBPUJHPMWTLQ-UHFFFAOYSA-N 2-cyclopentyl-7-hydroxy-1h-benzimidazole-4-carboxylic acid Chemical compound N1C=2C(C(=O)O)=CC=C(O)C=2N=C1C1CCCC1 OVWBPUJHPMWTLQ-UHFFFAOYSA-N 0.000 description 3
- HSZICKWKNHDWAD-UHFFFAOYSA-N 2-cyclopropyl-7-methoxy-1h-benzimidazol-4-amine Chemical compound N1C=2C(OC)=CC=C(N)C=2N=C1C1CC1 HSZICKWKNHDWAD-UHFFFAOYSA-N 0.000 description 3
- NTTTURJGCKSVGE-UHFFFAOYSA-N 7-methoxy-2-thiophen-2-yl-3h-benzimidazole-5-carboxylic acid Chemical compound N1C=2C(OC)=CC(C(O)=O)=CC=2N=C1C1=CC=CS1 NTTTURJGCKSVGE-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 description 3
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229960001340 histamine Drugs 0.000 description 3
- 150000001261 hydroxy acids Chemical class 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000000021 kinase assay Methods 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 238000011445 neoadjuvant hormone therapy Methods 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 2
- URCWFFJUMVIZQA-UHFFFAOYSA-N 1,3-bis(2-cyclopropyl-7-methoxy-1h-benzimidazol-4-yl)urea Chemical compound C1=2N=C(C3CC3)NC=2C(OC)=CC=C1NC(=O)NC(C=1N=2)=CC=C(OC)C=1NC=2C1CC1 URCWFFJUMVIZQA-UHFFFAOYSA-N 0.000 description 2
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 2
- SXOVYMCCZGKLGI-UHFFFAOYSA-N 1-(2-cyclopropyl-7-methoxy-1h-benzimidazol-4-yl)-3-(4-methoxyphenyl)urea Chemical compound C1=CC(OC)=CC=C1NC(=O)NC1=CC=C(OC)C2=C1N=C(C1CC1)N2 SXOVYMCCZGKLGI-UHFFFAOYSA-N 0.000 description 2
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 2
- DEURIUYJZZLADZ-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)ethanamine Chemical compound NCCC1=NC=CN1 DEURIUYJZZLADZ-UHFFFAOYSA-N 0.000 description 2
- CKLFJWXRWIQYOC-UHFFFAOYSA-N 2-(4-fluorophenyl)ethanamine Chemical compound NCCC1=CC=C(F)C=C1 CKLFJWXRWIQYOC-UHFFFAOYSA-N 0.000 description 2
- QIEMOKUVCNROKE-UHFFFAOYSA-N 2-(furan-2-yl)-7-hydroxy-n-[2-[(5-nitropyridin-2-yl)amino]ethyl]-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3OC=CC=3)NC=2C(O)=CC=C1C(=O)NCCNC1=CC=C([N+]([O-])=O)C=N1 QIEMOKUVCNROKE-UHFFFAOYSA-N 0.000 description 2
- LXMDEJJZMNUHHS-UHFFFAOYSA-N 2-(furan-2-yl)-7-methoxy-n-(1,3-thiazol-2-yl)-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3OC=CC=3)NC=2C(OC)=CC=C1C(=O)NC1=NC=CS1 LXMDEJJZMNUHHS-UHFFFAOYSA-N 0.000 description 2
- GEJVLAIJXQDLML-UHFFFAOYSA-N 2-(furan-2-yl)-7-methoxy-n-[2-(1-methylpyrrol-2-yl)ethyl]-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3OC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCC1=CC=CN1C GEJVLAIJXQDLML-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- QQDXOCYCKJVEPP-UHFFFAOYSA-N 2-[3-[1-(4-methylphenyl)sulfonylimidazol-2-yl]propyl]isoindole-1,3-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(CCCN2C(C3=CC=CC=C3C2=O)=O)=NC=C1 QQDXOCYCKJVEPP-UHFFFAOYSA-N 0.000 description 2
- QCEWNYUNJMJBCI-UHFFFAOYSA-N 2-cyclopropyl-7-methoxy-n-[2-(4-sulfamoylphenyl)ethyl]-1h-benzimidazole-4-carboxamide Chemical compound C1=2NC(C3CC3)=NC=2C(OC)=CC=C1C(=O)NCCC1=CC=C(S(N)(=O)=O)C=C1 QCEWNYUNJMJBCI-UHFFFAOYSA-N 0.000 description 2
- RTXLXMIUTNUIGC-UHFFFAOYSA-N 2-cyclopropyl-n-[2-(4-fluorophenyl)ethyl]-7-methoxy-1h-benzimidazole-4-carboxamide Chemical compound C1=2NC(C3CC3)=NC=2C(OC)=CC=C1C(=O)NCCC1=CC=C(F)C=C1 RTXLXMIUTNUIGC-UHFFFAOYSA-N 0.000 description 2
- HQNOODJDSFSURF-UHFFFAOYSA-N 3-(1h-imidazol-2-yl)propan-1-amine Chemical compound NCCCC1=NC=CN1 HQNOODJDSFSURF-UHFFFAOYSA-N 0.000 description 2
- HNHTUQFIYSEUMO-UHFFFAOYSA-N 3-[1-(4-methylphenyl)sulfonylimidazol-2-yl]propan-1-ol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(CCCO)=NC=C1 HNHTUQFIYSEUMO-UHFFFAOYSA-N 0.000 description 2
- LNPMZQXEPNWCMG-UHFFFAOYSA-N 4-(2-aminoethyl)aniline Chemical compound NCCC1=CC=C(N)C=C1 LNPMZQXEPNWCMG-UHFFFAOYSA-N 0.000 description 2
- FXNSVEQMUYPYJS-UHFFFAOYSA-N 4-(2-aminoethyl)benzenesulfonamide Chemical compound NCCC1=CC=C(S(N)(=O)=O)C=C1 FXNSVEQMUYPYJS-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- XVSGAPXSUQKKQJ-UHFFFAOYSA-N 7-fluoro-2-thiophen-2-yl-3h-benzimidazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=C(F)C=2NC=1C1=CC=CS1 XVSGAPXSUQKKQJ-UHFFFAOYSA-N 0.000 description 2
- PEELIBUMTXGKIM-UHFFFAOYSA-N 7-hydroxy-n-[2-(3-methoxyphenyl)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound COC1=CC=CC(CCNC(=O)C=2C=3N=C(NC=3C(O)=CC=2)C=2SC=CC=2)=C1 PEELIBUMTXGKIM-UHFFFAOYSA-N 0.000 description 2
- YNPZYIACHQGCJT-UHFFFAOYSA-N 7-hydroxy-n-[2-[(5-nitropyridin-2-yl)amino]ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCNC1=CC=C([N+]([O-])=O)C=N1 YNPZYIACHQGCJT-UHFFFAOYSA-N 0.000 description 2
- CEWDBJZCSBURSD-UHFFFAOYSA-N 7-methoxy-2-thiophen-2-yl-1h-benzimidazol-4-amine;hydrochloride Chemical compound Cl.N1C=2C(OC)=CC=C(N)C=2N=C1C1=CC=CS1 CEWDBJZCSBURSD-UHFFFAOYSA-N 0.000 description 2
- BVOPAEYMEDOKRZ-UHFFFAOYSA-N 7-methoxy-2-thiophen-2-yl-3h-benzimidazole-5-carboxamide Chemical compound N1C=2C(OC)=CC(C(N)=O)=CC=2N=C1C1=CC=CS1 BVOPAEYMEDOKRZ-UHFFFAOYSA-N 0.000 description 2
- MBIRMGLAOUIYQA-UHFFFAOYSA-N 7-methoxy-2-thiophen-2-yl-n-[2-[5-(trifluoromethyl)pyridin-2-yl]oxyethyl]-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCOC1=CC=C(C(F)(F)F)C=N1 MBIRMGLAOUIYQA-UHFFFAOYSA-N 0.000 description 2
- YYDDPZLBNSICAV-UHFFFAOYSA-N 7-methoxy-n-[2-(3-methylimidazol-4-yl)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCC1=CN=CN1C YYDDPZLBNSICAV-UHFFFAOYSA-N 0.000 description 2
- YKYVRHJEVIGDGY-UHFFFAOYSA-N 7-methoxy-n-[2-(pyridin-4-ylsulfonylamino)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCNS(=O)(=O)C1=CC=NC=C1 YKYVRHJEVIGDGY-UHFFFAOYSA-N 0.000 description 2
- XOHNBHXAPQLKBN-UHFFFAOYSA-N 7-methoxy-n-[2-[(4-methylbenzoyl)amino]ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCNC(=O)C1=CC=C(C)C=C1 XOHNBHXAPQLKBN-UHFFFAOYSA-N 0.000 description 2
- IQVCWYNOVLXABW-UHFFFAOYSA-N 7-methoxy-n-[3-(propan-2-ylamino)propyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N1C=2C(OC)=CC=C(C(=O)NCCCNC(C)C)C=2N=C1C1=CC=CS1 IQVCWYNOVLXABW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 2
- VPLLZMWJHRUCMF-UHFFFAOYSA-N methyl 2-cyclopentyl-7-methoxy-1h-benzimidazole-4-carboxylate Chemical compound N1C=2C(C(=O)OC)=CC=C(OC)C=2N=C1C1CCCC1 VPLLZMWJHRUCMF-UHFFFAOYSA-N 0.000 description 2
- PRGGQJGVQYYFGX-UHFFFAOYSA-N methyl 2-cyclopropyl-7-methoxy-1h-benzimidazole-4-carboxylate Chemical compound N1C=2C(C(=O)OC)=CC=C(OC)C=2N=C1C1CC1 PRGGQJGVQYYFGX-UHFFFAOYSA-N 0.000 description 2
- DSXKVMFEUNHVGE-UHFFFAOYSA-N methyl 3-[1-(4-methylphenyl)sulfonylimidazol-2-yl]prop-2-enoate Chemical compound COC(=O)C=CC1=NC=CN1S(=O)(=O)C1=CC=C(C)C=C1 DSXKVMFEUNHVGE-UHFFFAOYSA-N 0.000 description 2
- UNSGMGDVIYSRCM-UHFFFAOYSA-N methyl 3-[1-(4-methylphenyl)sulfonylimidazol-2-yl]propanoate Chemical compound COC(=O)CCC1=NC=CN1S(=O)(=O)C1=CC=C(C)C=C1 UNSGMGDVIYSRCM-UHFFFAOYSA-N 0.000 description 2
- VHIJRAZXPZVVMT-UHFFFAOYSA-N methyl 3-[[amino(cyclopentyl)methylidene]amino]-4-methoxybenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(OC)C(NC(=N)C2CCCC2)=C1 VHIJRAZXPZVVMT-UHFFFAOYSA-N 0.000 description 2
- ZPLDKFGQLDZAJL-UHFFFAOYSA-N methyl 3-[[amino(cyclopropyl)methylidene]amino]-4-methoxybenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(OC)C(NC(=N)C2CC2)=C1 ZPLDKFGQLDZAJL-UHFFFAOYSA-N 0.000 description 2
- QHLFPSCMDZCUPE-UHFFFAOYSA-N methyl 3-[[amino(furan-2-yl)methylidene]amino]-4-methoxybenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(OC)C(NC(=N)C=2OC=CC=2)=C1 QHLFPSCMDZCUPE-UHFFFAOYSA-N 0.000 description 2
- AHYAHJHNDLZBNZ-UHFFFAOYSA-N methyl 3-[[amino(phenyl)methylidene]amino]-4-methoxybenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(OC)C(NC(=N)C=2C=CC=CC=2)=C1 AHYAHJHNDLZBNZ-UHFFFAOYSA-N 0.000 description 2
- DLIXZLCMFADBDS-UHFFFAOYSA-N methyl 3-[[amino(thiophen-2-yl)methylidene]amino]-4-fluorobenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(F)C(NC(=N)C=2SC=CC=2)=C1 DLIXZLCMFADBDS-UHFFFAOYSA-N 0.000 description 2
- KLHIPTAXBMETKI-UHFFFAOYSA-N methyl 4-[[amino(thiophen-2-yl)methylidene]amino]-3-methoxybenzoate;hydrochloride Chemical compound Cl.COC1=CC(C(=O)OC)=CC=C1NC(=N)C1=CC=CS1 KLHIPTAXBMETKI-UHFFFAOYSA-N 0.000 description 2
- XZWKHHKDPCUEOZ-UHFFFAOYSA-N methyl 4-methoxy-3-(thiophene-2-carbonylamino)benzoate Chemical compound COC(=O)C1=CC=C(OC)C(NC(=O)C=2SC=CC=2)=C1 XZWKHHKDPCUEOZ-UHFFFAOYSA-N 0.000 description 2
- OUINOQYRLVBCMS-UHFFFAOYSA-N methyl 7-fluoro-2-thiophen-2-yl-3h-benzimidazole-4-carboxylate Chemical compound N=1C=2C(C(=O)OC)=CC=C(F)C=2NC=1C1=CC=CS1 OUINOQYRLVBCMS-UHFFFAOYSA-N 0.000 description 2
- YBKCCRRVBMZAOB-UHFFFAOYSA-N methyl 7-methoxy-2-phenyl-1h-benzimidazole-4-carboxylate Chemical compound N=1C=2C(C(=O)OC)=CC=C(OC)C=2NC=1C1=CC=CC=C1 YBKCCRRVBMZAOB-UHFFFAOYSA-N 0.000 description 2
- OKWMXUZNFRSEJX-UHFFFAOYSA-N methyl 7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxylate Chemical compound N=1C=2C(C(=O)OC)=CC=C(OC)C=2NC=1C1=CC=CS1 OKWMXUZNFRSEJX-UHFFFAOYSA-N 0.000 description 2
- WUZGRQPEXDLKQN-UHFFFAOYSA-N methyl 7-methoxy-2-thiophen-2-yl-3h-benzimidazole-5-carboxylate Chemical compound N=1C2=CC(C(=O)OC)=CC(OC)=C2NC=1C1=CC=CS1 WUZGRQPEXDLKQN-UHFFFAOYSA-N 0.000 description 2
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 2
- CJVFQZXNHIWPBZ-UHFFFAOYSA-N n-(2-acetamidoethyl)-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N1C=2C(OC)=CC=C(C(=O)NCCNC(C)=O)C=2N=C1C1=CC=CS1 CJVFQZXNHIWPBZ-UHFFFAOYSA-N 0.000 description 2
- HUOMQECEWYETBW-UHFFFAOYSA-N n-(2-cyclopropyl-7-methoxy-1h-benzimidazol-4-yl)-2-(4-methoxyphenyl)acetamide Chemical compound C1=CC(OC)=CC=C1CC(=O)NC1=CC=C(OC)C2=C1N=C(C1CC1)N2 HUOMQECEWYETBW-UHFFFAOYSA-N 0.000 description 2
- BOZMVONDDOSKJB-UHFFFAOYSA-N n-(3-imidazol-1-ylpropyl)-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCCN1C=CN=C1 BOZMVONDDOSKJB-UHFFFAOYSA-N 0.000 description 2
- GNQXGIRJZAGFLD-UHFFFAOYSA-N n-[(3,4-dimethoxyphenyl)methyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CNC(=O)C1=CC=C(OC)C2=C1N=C(C=1SC=CC=1)N2 GNQXGIRJZAGFLD-UHFFFAOYSA-N 0.000 description 2
- MDAPGWXHICTIHL-UHFFFAOYSA-N n-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]-2-(furan-2-yl)-7-methoxy-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3OC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCC=1C(C)=NOC=1C MDAPGWXHICTIHL-UHFFFAOYSA-N 0.000 description 2
- DCLDFGXUQVRFCZ-UHFFFAOYSA-N n-[2-(4-fluorophenyl)ethyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCC1=CC=C(F)C=C1 DCLDFGXUQVRFCZ-UHFFFAOYSA-N 0.000 description 2
- YEMDPAGCOOMZSE-UHFFFAOYSA-N n-[2-(4-hydroxyphenyl)ethyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCC1=CC=C(O)C=C1 YEMDPAGCOOMZSE-UHFFFAOYSA-N 0.000 description 2
- SXTFLHJIMWRWPZ-UHFFFAOYSA-N n-[2-(5-carbamoylpyridin-2-yl)oxyethyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCOC1=CC=C(C(N)=O)C=N1 SXTFLHJIMWRWPZ-UHFFFAOYSA-N 0.000 description 2
- UMNDDQAYXARJBV-UHFFFAOYSA-N n-[2-(benzenesulfonamido)ethyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCNS(=O)(=O)C1=CC=CC=C1 UMNDDQAYXARJBV-UHFFFAOYSA-N 0.000 description 2
- GETFDLMXWYOKKJ-UHFFFAOYSA-N n-[2-[(4-chlorophenyl)sulfonylamino]ethyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCNS(=O)(=O)C1=CC=C(Cl)C=C1 GETFDLMXWYOKKJ-UHFFFAOYSA-N 0.000 description 2
- SBECMSFCBVICPN-UHFFFAOYSA-N n-[2-[(5-aminopyridin-2-yl)amino]ethyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide;hydrochloride Chemical compound Cl.N1=CC(N)=CC=C1NCCNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 SBECMSFCBVICPN-UHFFFAOYSA-N 0.000 description 2
- 230000000626 neurodegenerative effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- HOBSFSMDYCMOLK-UHFFFAOYSA-N tert-butyl 3-[(4-methoxy-2-nitrobenzoyl)amino]piperidine-1-carboxylate Chemical compound [O-][N+](=O)C1=CC(OC)=CC=C1C(=O)NC1CN(C(=O)OC(C)(C)C)CCC1 HOBSFSMDYCMOLK-UHFFFAOYSA-N 0.000 description 2
- RNSJYMNAEDRFIR-UHFFFAOYSA-N tert-butyl n-(2-cyclopropyl-7-methoxy-1h-benzimidazol-4-yl)carbamate Chemical compound N1C=2C(OC)=CC=C(NC(=O)OC(C)(C)C)C=2N=C1C1CC1 RNSJYMNAEDRFIR-UHFFFAOYSA-N 0.000 description 2
- MLDSDVASYUUDLT-UHFFFAOYSA-N tert-butyl n-(3-oxopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC=O MLDSDVASYUUDLT-UHFFFAOYSA-N 0.000 description 2
- UNXMOKLGTAULFB-UHFFFAOYSA-N tert-butyl n-(7-methoxy-2-thiophen-2-yl-1h-benzimidazol-4-yl)carbamate Chemical compound N1C=2C(OC)=CC=C(NC(=O)OC(C)(C)C)C=2N=C1C1=CC=CS1 UNXMOKLGTAULFB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- QDZZDVQGBKTLHV-UHFFFAOYSA-N (2,4-difluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1F QDZZDVQGBKTLHV-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- ZQISRDCJNBUVMM-RXMQYKEDSA-N (2r)-2-amino-3-(1h-imidazol-5-yl)propan-1-ol Chemical compound OC[C@H](N)CC1=CN=CN1 ZQISRDCJNBUVMM-RXMQYKEDSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- JBULSURVMXPBNA-RXMQYKEDSA-N (2s)-2-amino-3,3-dimethylbutan-1-ol Chemical compound CC(C)(C)[C@H](N)CO JBULSURVMXPBNA-RXMQYKEDSA-N 0.000 description 1
- DIVNUTGTTIRPQA-UHFFFAOYSA-N (3,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1OC DIVNUTGTTIRPQA-UHFFFAOYSA-N 0.000 description 1
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 description 1
- BLFLXIVNUOHJEJ-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonylimidazole-2-carbaldehyde Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(C=O)=NC=C1 BLFLXIVNUOHJEJ-UHFFFAOYSA-N 0.000 description 1
- YKEQWSFVTHOPQU-UHFFFAOYSA-N 1-thiophen-2-ylbenzimidazole-4-carboxamide Chemical compound S1C(=CC=C1)N1C=NC2=C1C=CC=C2C(=O)N YKEQWSFVTHOPQU-UHFFFAOYSA-N 0.000 description 1
- JJDMKDXGNVJWCD-UHFFFAOYSA-N 1h-benzimidazole-4-carboxamide Chemical compound NC(=O)C1=CC=CC2=C1N=CN2 JJDMKDXGNVJWCD-UHFFFAOYSA-N 0.000 description 1
- AKWIAIDKXNKXDI-UHFFFAOYSA-N 1h-pyrrole-3-carboxamide Chemical compound NC(=O)C=1C=CNC=1 AKWIAIDKXNKXDI-UHFFFAOYSA-N 0.000 description 1
- ZMZSYUSDGRJZNT-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)acetonitrile Chemical compound C1=CC=C2SC(CC#N)=NC2=C1 ZMZSYUSDGRJZNT-UHFFFAOYSA-N 0.000 description 1
- CPAGZVLINCPJEH-UHFFFAOYSA-N 2-(1-methyl-1h-imidazol-5-yl)ethan-1-amine Chemical compound CN1C=NC=C1CCN CPAGZVLINCPJEH-UHFFFAOYSA-N 0.000 description 1
- ITFDYXKCBZEBDG-UHFFFAOYSA-N 2-(1-methylpyrrol-2-yl)ethanamine Chemical compound CN1C=CC=C1CCN ITFDYXKCBZEBDG-UHFFFAOYSA-N 0.000 description 1
- HOJDTRKLAOLNIT-UHFFFAOYSA-N 2-(3,5-dimethyl-1,2-oxazol-4-yl)ethanamine Chemical compound CC1=NOC(C)=C1CCN HOJDTRKLAOLNIT-UHFFFAOYSA-N 0.000 description 1
- GHKSKVKCKMGRDU-UHFFFAOYSA-N 2-(3-aminopropylamino)ethanol Chemical compound NCCCNCCO GHKSKVKCKMGRDU-UHFFFAOYSA-N 0.000 description 1
- WJBMRZAHTUFBGE-UHFFFAOYSA-N 2-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC(CCN)=C1 WJBMRZAHTUFBGE-UHFFFAOYSA-N 0.000 description 1
- CXJOONIFSVSFAD-UHFFFAOYSA-N 2-(4-methoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(CC(Cl)=O)C=C1 CXJOONIFSVSFAD-UHFFFAOYSA-N 0.000 description 1
- CWYDJVNQLOTFNE-UHFFFAOYSA-N 2-(4-methylphenyl)benzoyl chloride Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1C(Cl)=O CWYDJVNQLOTFNE-UHFFFAOYSA-N 0.000 description 1
- JIMLNOXLFHMJAE-UHFFFAOYSA-N 2-(furan-2-yl)-7-hydroxy-n-[2-(1-methylpyrrol-2-yl)ethyl]-1h-benzimidazole-4-carboxamide Chemical compound CN1C=CC=C1CCNC(=O)C1=CC=C(O)C2=C1N=C(C=1OC=CC=1)N2 JIMLNOXLFHMJAE-UHFFFAOYSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- JFZJMSDDOOAOIV-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1 JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 1
- SWMCGIYDIXUCLO-UHFFFAOYSA-N 2-cyclopropyl-n-(4-hydroxyphenyl)-7-methoxy-1h-benzimidazole-4-carboxamide Chemical compound C1=2NC(C3CC3)=NC=2C(OC)=CC=C1C(=O)NC1=CC=C(O)C=C1 SWMCGIYDIXUCLO-UHFFFAOYSA-N 0.000 description 1
- MWOFSHRVMPYTGX-UHFFFAOYSA-N 2-cyclopropyl-n-[2-(dimethylamino)ethyl]-7-hydroxy-1h-benzimidazole-4-carboxamide Chemical compound N1C=2C(C(=O)NCCN(C)C)=CC=C(O)C=2N=C1C1CC1 MWOFSHRVMPYTGX-UHFFFAOYSA-N 0.000 description 1
- 125000006149 2-ethylbutyl sulfonyl group Chemical group 0.000 description 1
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 description 1
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- HVLUYXIJZLDNIS-UHFFFAOYSA-N 2-thiophen-2-ylethanamine Chemical compound NCCC1=CC=CS1 HVLUYXIJZLDNIS-UHFFFAOYSA-N 0.000 description 1
- KQIGMPWTAHJUMN-VKHMYHEASA-N 3-aminopropane-1,2-diol Chemical compound NC[C@H](O)CO KQIGMPWTAHJUMN-VKHMYHEASA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 1
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 1
- 125000004919 3-methyl-2-pentyl group Chemical group CC(C(C)*)CC 0.000 description 1
- 125000004921 3-methyl-3-pentyl group Chemical group CC(CC)(CC)* 0.000 description 1
- FNLQDVXHDNFXIY-UHFFFAOYSA-N 3h-benzimidazole-5-carboxamide Chemical compound NC(=O)C1=CC=C2NC=NC2=C1 FNLQDVXHDNFXIY-UHFFFAOYSA-N 0.000 description 1
- LMLXMJPJCSUFAB-UHFFFAOYSA-N 4-(3-aminopropyl)-1,4-dihydropyrazol-5-one Chemical compound NCCCC1C=NNC1=O LMLXMJPJCSUFAB-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- DVZBWONCSHFMMM-UHFFFAOYSA-N 4-methoxy-2-nitrobenzoic acid Chemical compound COC1=CC=C(C(O)=O)C([N+]([O-])=O)=C1 DVZBWONCSHFMMM-UHFFFAOYSA-N 0.000 description 1
- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 1
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 1
- ZIJAZUBWHAZHPL-UHFFFAOYSA-N 6-chloropyridine-3-carboxamide Chemical compound NC(=O)C1=CC=C(Cl)N=C1 ZIJAZUBWHAZHPL-UHFFFAOYSA-N 0.000 description 1
- HIEVUCALPWFEFA-UHFFFAOYSA-N 60814-16-6 Chemical compound NCCOC1=CC=C([N+]([O-])=O)C=C1 HIEVUCALPWFEFA-UHFFFAOYSA-N 0.000 description 1
- ATHLCHSPHOTZSW-UHFFFAOYSA-N 7-hydroxy-2-thiophen-2-yl-1H-benzimidazole-4-carboxamide Chemical compound OC1=CC=C(C2=C1NC(=N2)C=1SC=CC=1)C(=O)N ATHLCHSPHOTZSW-UHFFFAOYSA-N 0.000 description 1
- VDTJTBXXNGFVFO-UHFFFAOYSA-N 7-hydroxy-2-thiophen-2-yl-n-[2-[5-(trifluoromethyl)pyridin-2-yl]oxyethyl]-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCOC1=CC=C(C(F)(F)F)C=N1 VDTJTBXXNGFVFO-UHFFFAOYSA-N 0.000 description 1
- YBFGBABPODCQNN-UHFFFAOYSA-N 7-hydroxy-n-[2-(3-methylimidazol-4-yl)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound CN1C=NC=C1CCNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 YBFGBABPODCQNN-UHFFFAOYSA-N 0.000 description 1
- PMQBYSMSFGQXEX-UHFFFAOYSA-N 7-hydroxy-n-[2-(4-hydroxyphenyl)ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(O)=CC=C1CCNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 PMQBYSMSFGQXEX-UHFFFAOYSA-N 0.000 description 1
- YDRDTJACXJKVCD-UHFFFAOYSA-N 7-hydroxy-n-[2-[(4-methylbenzoyl)amino]ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1C(=O)NCCNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 YDRDTJACXJKVCD-UHFFFAOYSA-N 0.000 description 1
- CTAQQUCNSORLGC-UHFFFAOYSA-N 7-hydroxy-n-[2-[4-[(4-methylphenyl)sulfonylamino]phenoxy]ethyl]-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(C=C1)=CC=C1OCCNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 CTAQQUCNSORLGC-UHFFFAOYSA-N 0.000 description 1
- DIGZMTAFOACVBW-UHFFFAOYSA-N 7-phenylmethoxy-1h-indole Chemical compound C=1C=CC=2C=CNC=2C=1OCC1=CC=CC=C1 DIGZMTAFOACVBW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010001483 Glycogen Synthase Proteins 0.000 description 1
- 101150113453 Gsk3a gene Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- BXRMEWOQUXOLDH-LURJTMIESA-N L-Histidine methyl ester Chemical compound COC(=O)[C@@H](N)CC1=CN=CN1 BXRMEWOQUXOLDH-LURJTMIESA-N 0.000 description 1
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- TYMRLRRVMHJFTF-UHFFFAOYSA-N Mafenide Chemical compound NCC1=CC=C(S(N)(=O)=O)C=C1 TYMRLRRVMHJFTF-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 101710115937 Microtubule-associated protein tau Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 description 1
- 101100513046 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) eth-1 gene Proteins 0.000 description 1
- NDPLWWAODFQDRM-UHFFFAOYSA-N O1C(=CC=C1)C1=NC2=C(N1CCC1=CC=CC=C1)C(=CC=C2)O Chemical compound O1C(=CC=C1)C1=NC2=C(N1CCC1=CC=CC=C1)C(=CC=C2)O NDPLWWAODFQDRM-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- 108010001441 Phosphopeptides Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000034799 Tauopathies Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- SVPZJHKVRMRREG-UHFFFAOYSA-N cyclopentanecarbonitrile Chemical compound N#CC1CCCC1 SVPZJHKVRMRREG-UHFFFAOYSA-N 0.000 description 1
- AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000003104 endogenous depression Diseases 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000006951 hyperphosphorylation Effects 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 125000006301 indolyl methyl group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000008040 ionic compounds Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 229940071264 lithium citrate Drugs 0.000 description 1
- WJSIUCDMWSDDCE-UHFFFAOYSA-K lithium citrate (anhydrous) Chemical compound [Li+].[Li+].[Li+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WJSIUCDMWSDDCE-UHFFFAOYSA-K 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- KCUNTYMNJVXYKZ-JTQLQIEISA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 KCUNTYMNJVXYKZ-JTQLQIEISA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
- ANSUDRATXSJBLY-UHFFFAOYSA-N methyl 2-amino-3-hydroxypropanoate Chemical compound COC(=O)C(N)CO ANSUDRATXSJBLY-UHFFFAOYSA-N 0.000 description 1
- SIPPUXPIJXLNKR-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)-2-[(7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carbonyl)amino]propanoate Chemical compound C=1C=C(O)C=2NC(C=3SC=CC=3)=NC=2C=1C(=O)NC(C(=O)OC)CC1=CC=C(O)C=C1 SIPPUXPIJXLNKR-UHFFFAOYSA-N 0.000 description 1
- UMDBYBUACBGSNK-UHFFFAOYSA-N methyl 3-[[amino(thiophen-2-yl)methylidene]amino]-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(NC(=N)C=2SC=CC=2)=C1 UMDBYBUACBGSNK-UHFFFAOYSA-N 0.000 description 1
- ABELEDYNIKPYTP-UHFFFAOYSA-N methyl 3-amino-4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C(N)=C1 ABELEDYNIKPYTP-UHFFFAOYSA-N 0.000 description 1
- DJLFOMMCQBAMAA-UHFFFAOYSA-N methyl 4-amino-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(N)C(OC)=C1 DJLFOMMCQBAMAA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- ODHSPTHLPCXPTL-UHFFFAOYSA-N n'-(5-nitropyridin-2-yl)ethane-1,2-diamine Chemical compound NCCNC1=CC=C([N+]([O-])=O)C=N1 ODHSPTHLPCXPTL-UHFFFAOYSA-N 0.000 description 1
- KFDIDIIKNMZLRZ-UHFFFAOYSA-N n'-propan-2-ylpropane-1,3-diamine Chemical compound CC(C)NCCCN KFDIDIIKNMZLRZ-UHFFFAOYSA-N 0.000 description 1
- TYHXIJJQIJKFSO-UHFFFAOYSA-N n'-pyridin-2-ylethane-1,2-diamine Chemical compound NCCNC1=CC=CC=N1 TYHXIJJQIJKFSO-UHFFFAOYSA-N 0.000 description 1
- MWEBCGQFQBAAJP-UHFFFAOYSA-N n-(2-aminoethyl)-4-chlorobenzenesulfonamide Chemical compound NCCNS(=O)(=O)C1=CC=C(Cl)C=C1 MWEBCGQFQBAAJP-UHFFFAOYSA-N 0.000 description 1
- IYTURFXZHKVZGN-UHFFFAOYSA-N n-(2-aminoethyl)-4-chlorobenzenesulfonamide;hydrochloride Chemical compound Cl.NCCNS(=O)(=O)C1=CC=C(Cl)C=C1 IYTURFXZHKVZGN-UHFFFAOYSA-N 0.000 description 1
- IISCWLATEHABQS-UHFFFAOYSA-N n-(2-aminoethyl)-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NCCN)C=C1 IISCWLATEHABQS-UHFFFAOYSA-N 0.000 description 1
- DAKZISABEDGGSV-UHFFFAOYSA-N n-(2-aminoethyl)acetamide Chemical compound CC(=O)NCCN DAKZISABEDGGSV-UHFFFAOYSA-N 0.000 description 1
- BCGXHHYBXMQECD-UHFFFAOYSA-N n-(2-aminoethyl)benzamide;hydrochloride Chemical compound Cl.NCCNC(=O)C1=CC=CC=C1 BCGXHHYBXMQECD-UHFFFAOYSA-N 0.000 description 1
- JVFJSUCEQDCCAH-UHFFFAOYSA-N n-(2-aminoethyl)benzenesulfonamide Chemical compound NCCNS(=O)(=O)C1=CC=CC=C1 JVFJSUCEQDCCAH-UHFFFAOYSA-N 0.000 description 1
- NTENADQOAWUTOH-UHFFFAOYSA-N n-(2-aminoethyl)benzenesulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCCNS(=O)(=O)C1=CC=CC=C1 NTENADQOAWUTOH-UHFFFAOYSA-N 0.000 description 1
- KXBXVEGOHACSKW-UHFFFAOYSA-N n-(2-aminoethyl)pyridine-4-sulfonamide Chemical compound NCCNS(=O)(=O)C1=CC=NC=C1 KXBXVEGOHACSKW-UHFFFAOYSA-N 0.000 description 1
- AYZAQJGTNSWWBM-UHFFFAOYSA-N n-(2-aminoethyl)pyridine-4-sulfonamide;dihydrochloride Chemical compound Cl.Cl.NCCNS(=O)(=O)C1=CC=NC=C1 AYZAQJGTNSWWBM-UHFFFAOYSA-N 0.000 description 1
- LTGRYMCRXRFVCZ-UHFFFAOYSA-N n-(2-hydroxyethyl)-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N1C=2C(OC)=CC=C(C(=O)NCCO)C=2N=C1C1=CC=CS1 LTGRYMCRXRFVCZ-UHFFFAOYSA-N 0.000 description 1
- JHMDPDAKHZMBFU-UHFFFAOYSA-N n-(4-methoxyphenyl)carbamoyl chloride Chemical compound COC1=CC=C(NC(Cl)=O)C=C1 JHMDPDAKHZMBFU-UHFFFAOYSA-N 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- IOOARBMSXOAWLS-UHFFFAOYSA-N n-[(3,4-dihydroxyphenyl)methyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=C(O)C(O)=CC=C1CNC(=O)C1=CC=C(O)C2=C1N=C(C=1SC=CC=1)N2 IOOARBMSXOAWLS-UHFFFAOYSA-N 0.000 description 1
- WGWOZONQSDBZKW-UHFFFAOYSA-N n-[2-(1h-imidazol-2-yl)ethyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCC1=NC=CN1 WGWOZONQSDBZKW-UHFFFAOYSA-N 0.000 description 1
- HZLCGULYHQFQJG-UHFFFAOYSA-N n-[2-(1h-imidazol-5-yl)ethyl]-7-methoxy-2-thiophen-2-yl-3h-benzimidazole-5-carboxamide Chemical compound N1C=2C(OC)=CC(C(=O)NCCC=3NC=NC=3)=CC=2N=C1C1=CC=CS1 HZLCGULYHQFQJG-UHFFFAOYSA-N 0.000 description 1
- WWLAAJSXEXBHPG-UHFFFAOYSA-N n-[2-(1h-imidazol-5-yl)ethyl]-7-phenylmethoxy-1h-indole-3-carboxamide Chemical compound C=1NC2=C(OCC=3C=CC=CC=3)C=CC=C2C=1C(=O)NCCC1=CN=CN1 WWLAAJSXEXBHPG-UHFFFAOYSA-N 0.000 description 1
- NBKMAQQGBPQUAH-UHFFFAOYSA-N n-[2-(3,4-dihydroxyphenyl)ethyl]-2-(furan-2-yl)-7-hydroxy-1h-benzimidazole-4-carboxamide Chemical compound C1=C(O)C(O)=CC=C1CCNC(=O)C1=CC=C(O)C2=C1N=C(C=1OC=CC=1)N2 NBKMAQQGBPQUAH-UHFFFAOYSA-N 0.000 description 1
- PAPUOZOKUQXUCV-UHFFFAOYSA-N n-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]-2-(furan-2-yl)-7-hydroxy-1h-benzimidazole-4-carboxamide Chemical compound CC1=NOC(C)=C1CCNC(=O)C1=CC=C(O)C2=C1N=C(C=1OC=CC=1)N2 PAPUOZOKUQXUCV-UHFFFAOYSA-N 0.000 description 1
- MLTIVPRJLZLLPK-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound N1C=2C(OC)=CC=C(C(=O)NCCN(C)C)C=2N=C1C1=CC=CS1 MLTIVPRJLZLLPK-UHFFFAOYSA-N 0.000 description 1
- JOHGYBMIJBITFP-UHFFFAOYSA-N n-[2-[(4-chlorophenyl)sulfonylamino]ethyl]-7-hydroxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(O)=CC=C1C(=O)NCCNS(=O)(=O)C1=CC=C(Cl)C=C1 JOHGYBMIJBITFP-UHFFFAOYSA-N 0.000 description 1
- YUESKMWWLICRQR-UHFFFAOYSA-N n-[2-[(5-aminopyridin-2-yl)amino]ethyl]-2-(furan-2-yl)-7-hydroxy-1h-benzimidazole-4-carboxamide;hydrochloride Chemical compound Cl.N1=CC(N)=CC=C1NCCNC(=O)C1=CC=C(O)C2=C1N=C(C=1OC=CC=1)N2 YUESKMWWLICRQR-UHFFFAOYSA-N 0.000 description 1
- YIRIHJCPYLRLBV-UHFFFAOYSA-N n-[3-(1h-imidazol-2-yl)propyl]-7-methoxy-2-thiophen-2-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=2N=C(C=3SC=CC=3)NC=2C(OC)=CC=C1C(=O)NCCCC1=NC=CN1 YIRIHJCPYLRLBV-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006126 n-butyl sulfonyl group Chemical group 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- NHMOJCOXIZRTRR-UHFFFAOYSA-N pyridine-4-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=NC=C1 NHMOJCOXIZRTRR-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000007261 regionalization Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 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
- 239000011734 sodium Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LSDBSWXWUNOJKJ-UHFFFAOYSA-N tert-butyl 3-[(2-amino-4-methoxybenzoyl)amino]piperidine-1-carboxylate Chemical compound NC1=CC(OC)=CC=C1C(=O)NC1CN(C(=O)OC(C)(C)C)CCC1 LSDBSWXWUNOJKJ-UHFFFAOYSA-N 0.000 description 1
- AKQXKEBCONUWCL-UHFFFAOYSA-N tert-butyl 3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)C1 AKQXKEBCONUWCL-UHFFFAOYSA-N 0.000 description 1
- XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 1
- JZSSQQFLTWLZEM-UHFFFAOYSA-N tert-butyl n-[2-(4,5-dihydro-1h-imidazol-2-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCC1=NCCN1 JZSSQQFLTWLZEM-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- LOIYMIARKYCTBW-OWOJBTEDSA-N trans-urocanic acid Chemical compound OC(=O)\C=C\C1=CNC=N1 LOIYMIARKYCTBW-OWOJBTEDSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/41—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
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8477008P | 2008-07-30 | 2008-07-30 | |
| US61/084,770 | 2008-07-30 | ||
| PCT/US2009/052225 WO2010014794A1 (en) | 2008-07-30 | 2009-07-30 | Benzoimidazole derivatives and glycogen synthase kinase-3 beta inhibitors containing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2732280A1 true CA2732280A1 (en) | 2010-02-04 |
Family
ID=41610727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2732280A Abandoned CA2732280A1 (en) | 2008-07-30 | 2009-07-30 | Benzoimidazole derivatives and glycogen synthase kinase-3 beta inhibitors containing the same |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20110190351A1 (enExample) |
| EP (1) | EP2309855A4 (enExample) |
| JP (1) | JP2011529903A (enExample) |
| KR (1) | KR20110040958A (enExample) |
| CN (1) | CN102170785A (enExample) |
| AU (1) | AU2009276548A1 (enExample) |
| BR (1) | BRPI0916726A2 (enExample) |
| CA (1) | CA2732280A1 (enExample) |
| CO (1) | CO6351688A2 (enExample) |
| IL (1) | IL210863A0 (enExample) |
| MX (1) | MX2011001170A (enExample) |
| RU (1) | RU2011107227A (enExample) |
| WO (1) | WO2010014794A1 (enExample) |
| ZA (1) | ZA201101160B (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009158118A2 (en) | 2008-05-30 | 2009-12-30 | University Of Notre Dame Du Lac | Anti-bacterial agents from benzo[d]heterocyclic scaffolds for prevention and treatment of multidrug resistant bacteria |
| CN101619058A (zh) * | 2009-01-08 | 2010-01-06 | 上海交通大学 | 一种苯并咪唑-4-酰胺型衍生物 |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| SG11201604639YA (en) * | 2013-12-12 | 2016-07-28 | Univ Tsukuba | Sulfonamide derivative or pharmaceutically acceptable acid addition salt thereof |
| CN105461722B (zh) * | 2014-09-04 | 2019-05-10 | 欣凯医药化工中间体（上海）有限公司 | 一种脱氮嘌呤类化合物及其衍生物及其制备方法和应用 |
| WO2016133160A1 (ja) * | 2015-02-19 | 2016-08-25 | 国立大学法人筑波大学 | スルホンアミド誘導体またはその薬学的に許容される酸付加塩 |
| US20240132485A1 (en) * | 2020-10-16 | 2024-04-25 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Heterocyclic cullin ring ubiquitin ligase compounds and uses thereof |
| WO2024014851A1 (ko) * | 2022-07-12 | 2024-01-18 | 주식회사 넥스트젠바이오사이언스 | Hif-1 단백질 억제제로서의 신규한 퓨린 유도체 화합물 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0178413A1 (en) * | 1984-08-17 | 1986-04-23 | Beecham Group Plc | Benzimidazoles |
| FR2699816B1 (fr) * | 1992-12-30 | 1995-03-03 | Oreal | Compositions tinctoriales pour fibres kératiniques à base de paraphénylènediamines, de métaphénylènediamines et de dérivés du benzimidazole, et procédé de teinture les mettant en Óoeuvre. |
| JP2004536113A (ja) * | 2001-07-03 | 2004-12-02 | カイロン コーポレイション | チロシンキナーゼおよびセリン／スレオニンキナーゼのインヒビターとしてのインダゾールベンズイミダゾール化合物 |
| KR20040084896A (ko) * | 2002-02-06 | 2004-10-06 | 버텍스 파마슈티칼스 인코포레이티드 | Ｇｓｋ-3의 억제제로서 유용한 헤테로아릴 화합물 |
| WO2004065370A1 (en) * | 2003-01-23 | 2004-08-05 | Crystalgenomics, Inc. | Glycogen synthase kinase 3beta inhibitor, composition and process for the preparation thereof |
| CN102271514A (zh) * | 2008-10-30 | 2011-12-07 | 肿瘤疗法科学股份有限公司 | 7-羟基-苯并咪唑-4-基-甲酮衍生物以及包含其的pbk抑制剂 |
| RU2011124960A (ru) * | 2008-11-20 | 2012-12-27 | Онкотерпи Сайенс, Инк. | Ингибиторы гликогенсинтаза-киназы 3-бета, содержащие производные 7-гидроксибензоимидазол-4-илметанова |
-
2009
- 2009-07-30 EP EP09803582A patent/EP2309855A4/en active Pending
- 2009-07-30 AU AU2009276548A patent/AU2009276548A1/en not_active Withdrawn
- 2009-07-30 KR KR1020117004602A patent/KR20110040958A/ko not_active Withdrawn
- 2009-07-30 CN CN2009801387112A patent/CN102170785A/zh not_active Withdrawn
- 2009-07-30 US US13/056,591 patent/US20110190351A1/en not_active Abandoned
- 2009-07-30 CA CA2732280A patent/CA2732280A1/en not_active Abandoned
- 2009-07-30 RU RU2011107227/13A patent/RU2011107227A/ru not_active Application Discontinuation
- 2009-07-30 WO PCT/US2009/052225 patent/WO2010014794A1/en not_active Ceased
- 2009-07-30 MX MX2011001170A patent/MX2011001170A/es unknown
- 2009-07-30 JP JP2011521313A patent/JP2011529903A/ja not_active Withdrawn
- 2009-07-30 BR BRPI0916726A patent/BRPI0916726A2/pt not_active IP Right Cessation
-
2011
- 2011-01-25 IL IL210863A patent/IL210863A0/en unknown
- 2011-02-08 CO CO11014386A patent/CO6351688A2/es not_active Application Discontinuation
- 2011-02-14 ZA ZA2011/01160A patent/ZA201101160B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP2309855A4 (en) | 2012-06-27 |
| US20110190351A1 (en) | 2011-08-04 |
| RU2011107227A (ru) | 2012-09-10 |
| IL210863A0 (en) | 2011-04-28 |
| EP2309855A1 (en) | 2011-04-20 |
| KR20110040958A (ko) | 2011-04-20 |
| CN102170785A (zh) | 2011-08-31 |
| MX2011001170A (es) | 2011-04-05 |
| JP2011529903A (ja) | 2011-12-15 |
| WO2010014794A1 (en) | 2010-02-04 |
| BRPI0916726A2 (pt) | 2017-07-04 |
| CO6351688A2 (es) | 2011-12-20 |
| AU2009276548A1 (en) | 2010-02-04 |
| ZA201101160B (en) | 2011-10-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009276548A1 (en) | Benzoimidazole derivatives and glycogen synthase kinase-3 beta inhibitors containing the same | |
| US9622991B2 (en) | Hematopoietic growth factor mimetic small molecule compounds and their uses | |
| JP5878859B2 (ja) | ヒストンデアセチラーゼ（ｈｄａｃ）阻害剤としての複素環誘導体 | |
| CN102803252B (zh) | 用于治疗神经退化性疾病的吲哚酰胺衍生物及其相关化合物 | |
| AU2012229813B2 (en) | Sulfonamide compounds having TRPM8 antagonistic activity | |
| US20140243324A1 (en) | Use of hematopoietic growth factor mimetics | |
| CN102008459B (zh) | 抗菌剂 | |
| AU2004207740A1 (en) | Indole-derivative modulators of steroid hormone nuclear receptors | |
| EP1828169A2 (en) | Urea inhibitors of map kinases | |
| JP2011529903A5 (enExample) | ||
| JP2010533725A (ja) | ヒスタミン‐３（ｈ３）受容体としてのアミノアルキルアゾール化合物 | |
| US20080015222A1 (en) | New Heterocyclic Amides | |
| JP2012509249A (ja) | ７−ヒドロキシ−ベンゾイミダゾール−４−イル−メタノン誘導体を含むグリコーゲン合成酵素キナーゼ−３ベータ阻害剤 | |
| JP2009509931A (ja) | ヒストンデアセチラーゼ（ｈｄａｃ）阻害剤としてのアミノ酸誘導体 | |
| CN110105286A (zh) | 一种含有脲素骨架的取代杂环类化合物及其制备方法和用途 | |
| EP3634406B1 (en) | 3,4,5-trisubstituted-1,2,4-triazoles and 3,4,5-trisubstituted-3-thio-1,2,4-triazoles and uses thereof | |
| EP1948616B1 (en) | 2-(benzimidazol-1-yl)-acetamide biaryl derivatives and their use as inhibitors of the trpv1 receptor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20130730 |