HRP980369A2 - 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives - Google Patents
2-(4-bromo or 4-iodo phenylamino) benzoic acid derivativesInfo
- Publication number
- HRP980369A2 HRP980369A2 HR60/051,433A HRP980369A HRP980369A2 HR P980369 A2 HRP980369 A2 HR P980369A2 HR P980369 A HRP980369 A HR P980369A HR P980369 A2 HRP980369 A2 HR P980369A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- iodo
- phenylamino
- benzamide
- fluoro
- Prior art date
Links
- -1 4-iodo phenylamino Chemical group 0.000 title claims description 81
- 150000001558 benzoic acid derivatives Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 92
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims description 29
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 239000011737 fluorine Chemical group 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 239000000460 chlorine Chemical group 0.000 claims description 17
- 241000124008 Mammalia Species 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 230000002062 proliferating effect Effects 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- 229910052801 chlorine Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 208000037803 restenosis Diseases 0.000 claims description 9
- 201000004681 Psoriasis Diseases 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Substances OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 7
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
- GUAFZVVAOQFCPJ-UHFFFAOYSA-N 5-bromo-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCO GUAFZVVAOQFCPJ-UHFFFAOYSA-N 0.000 claims description 6
- DMXADGCWZHCXBU-UHFFFAOYSA-N 5-chloro-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NCCO DMXADGCWZHCXBU-UHFFFAOYSA-N 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- IIJDQEBBOFOXKL-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(O)=O IIJDQEBBOFOXKL-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- WRIPZDWCGAIYEF-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-5-nitro-n-[(4-sulfamoylphenyl)methyl]benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NCC1=CC=C(S(N)(=O)=O)C=C1 WRIPZDWCGAIYEF-UHFFFAOYSA-N 0.000 claims description 4
- LFKXETJHTXTXSA-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-5-nitrobenzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(O)=O LFKXETJHTXTXSA-UHFFFAOYSA-N 0.000 claims description 4
- XKRVQEHFHLIYHN-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-n-methyl-5-nitro-n-phenylbenzamide Chemical compound C=1C=CC=CC=1N(C)C(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(I)C=C1C XKRVQEHFHLIYHN-UHFFFAOYSA-N 0.000 claims description 4
- DSFQOJWTJQNGSU-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-[(4-sulfamoylphenyl)methyl]benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCC1=CC=C(S(N)(=O)=O)C=C1 DSFQOJWTJQNGSU-UHFFFAOYSA-N 0.000 claims description 4
- YNAWORHNPLOBBU-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-methyl-n-phenylbenzamide Chemical compound C=1C=CC=CC=1N(C)C(=O)C1=CC(Br)=CC=C1NC1=CC=C(I)C=C1C YNAWORHNPLOBBU-UHFFFAOYSA-N 0.000 claims description 4
- AANZSIPSXXHMRM-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NOCC1=CC=CC=C1 AANZSIPSXXHMRM-UHFFFAOYSA-N 0.000 claims description 4
- IHCADDZQYYEXFH-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(O)=O IHCADDZQYYEXFH-UHFFFAOYSA-N 0.000 claims description 4
- VBFVICYZHVZQIF-UHFFFAOYSA-N 5-bromo-n-cyclopropyl-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NC1CC1 VBFVICYZHVZQIF-UHFFFAOYSA-N 0.000 claims description 4
- MFISPQKUQORGHB-UHFFFAOYSA-N 5-chloro-2-(4-iodo-2-methylanilino)-n-methyl-n-phenylbenzamide Chemical compound C=1C=CC=CC=1N(C)C(=O)C1=CC(Cl)=CC=C1NC1=CC=C(I)C=C1C MFISPQKUQORGHB-UHFFFAOYSA-N 0.000 claims description 4
- NRQYGGWYEHEXEJ-UHFFFAOYSA-N 5-chloro-n-cyclopropyl-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NC1CC1 NRQYGGWYEHEXEJ-UHFFFAOYSA-N 0.000 claims description 4
- PJCPYFYKAWDPLX-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-[(4-sulfamoylphenyl)methyl]benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCC1=CC=C(S(N)(=O)=O)C=C1 PJCPYFYKAWDPLX-UHFFFAOYSA-N 0.000 claims description 4
- KCOUCDQMKMTOGV-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-methyl-n-phenylbenzamide Chemical compound C=1C=CC=CC=1N(C)C(=O)C1=CC(F)=CC=C1NC1=CC=C(I)C=C1C KCOUCDQMKMTOGV-UHFFFAOYSA-N 0.000 claims description 4
- CCGNHTHRIVEZPG-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NOCC1=CC=CC=C1 CCGNHTHRIVEZPG-UHFFFAOYSA-N 0.000 claims description 4
- YSXVOTVVUSIKNI-UHFFFAOYSA-N 5-fluoro-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCO YSXVOTVVUSIKNI-UHFFFAOYSA-N 0.000 claims description 4
- CLOSFYSFDCNULT-UHFFFAOYSA-N 5-iodo-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NOCC1=CC=CC=C1 CLOSFYSFDCNULT-UHFFFAOYSA-N 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- RYOCQJVSICWPKA-UHFFFAOYSA-N n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NCCO RYOCQJVSICWPKA-UHFFFAOYSA-N 0.000 claims description 4
- JDQKKPHXLMZTFM-UHFFFAOYSA-N n-(2-hydroxyethyl)-5-iodo-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NCCO JDQKKPHXLMZTFM-UHFFFAOYSA-N 0.000 claims description 4
- IDXFBAOJNKCQTB-UHFFFAOYSA-N n-cyclopropyl-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NC1CC1 IDXFBAOJNKCQTB-UHFFFAOYSA-N 0.000 claims description 4
- APDFSUINPPLQLM-UHFFFAOYSA-N n-cyclopropyl-5-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NC1CC1 APDFSUINPPLQLM-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- VXBGETLMHVNAMH-UHFFFAOYSA-N 2-[[5-chloro-2-(4-iodo-2-methylanilino)benzoyl]amino]acetic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NCC(O)=O VXBGETLMHVNAMH-UHFFFAOYSA-N 0.000 claims description 3
- XRNCNLRJMNWXRG-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(O)=O XRNCNLRJMNWXRG-UHFFFAOYSA-N 0.000 claims description 3
- FYFHVQLFQOKLEM-UHFFFAOYSA-N 4-chloro-4-iodo-6-methyl-6-(2h-tetrazol-5-yl)cyclohex-2-en-1-amine Chemical compound N1=NNN=C1C1(C)CC(Cl)(I)C=CC1N FYFHVQLFQOKLEM-UHFFFAOYSA-N 0.000 claims description 3
- DSNSWZOBIUQUBS-UHFFFAOYSA-N 5-bromo-3,4-difluoro-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NCCO DSNSWZOBIUQUBS-UHFFFAOYSA-N 0.000 claims description 3
- MBXXUKAZBOOXOL-UHFFFAOYSA-N 5-chloro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(O)=O MBXXUKAZBOOXOL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 3
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 201000004983 autoimmune atherosclerosis Diseases 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- IWZZOJQMYWDXJN-UHFFFAOYSA-N 2,3,5-trifluoro-4-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C=C(C(O)=O)C(F)=C1F IWZZOJQMYWDXJN-UHFFFAOYSA-N 0.000 claims description 2
- UDMYBSQMRDBEIC-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-hydroxyethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCO UDMYBSQMRDBEIC-UHFFFAOYSA-N 0.000 claims description 2
- QBTVPUBNRWFMGL-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-morpholin-4-ylethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCN1CCOCC1 QBTVPUBNRWFMGL-UHFFFAOYSA-N 0.000 claims description 2
- PFLMFENBMHGHFI-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-phenylethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCC1=CC=CC=C1 PFLMFENBMHGHFI-UHFFFAOYSA-N 0.000 claims description 2
- YGHCZGICKAIMTC-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-pyridin-4-ylethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCC1=CC=NC=C1 YGHCZGICKAIMTC-UHFFFAOYSA-N 0.000 claims description 2
- JILKHIVXSCYZRF-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCN1CCCC1 JILKHIVXSCYZRF-UHFFFAOYSA-N 0.000 claims description 2
- JGKIBUDEERWECG-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-thiophen-2-ylethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCC1=CC=CS1 JGKIBUDEERWECG-UHFFFAOYSA-N 0.000 claims description 2
- MPKKNJJTFVARIP-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(3-hydroxypropyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCCO MPKKNJJTFVARIP-UHFFFAOYSA-N 0.000 claims description 2
- FSCLSXYRUIVDGC-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(pyridin-4-ylmethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCC1=CC=NC=C1 FSCLSXYRUIVDGC-UHFFFAOYSA-N 0.000 claims description 2
- OPSQYIMKGZTWMH-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-5-methylbenzoic acid Chemical compound OC(=O)C1=CC(C)=CC=C1NC1=CC=C(I)C=C1C OPSQYIMKGZTWMH-UHFFFAOYSA-N 0.000 claims description 2
- CRPNAKOBOPIKFH-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-5-nitro-n-(pyridin-4-ylmethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NCC1=CC=NC=C1 CRPNAKOBOPIKFH-UHFFFAOYSA-N 0.000 claims description 2
- BJULGELJDWFRAX-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-5-nitro-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NOCC1=CC=CC=C1 BJULGELJDWFRAX-UHFFFAOYSA-N 0.000 claims description 2
- KLYXRBOQQVDCRR-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-n-[(3-methylphenyl)methyl]-5-nitrobenzamide Chemical compound CC1=CC=CC(CNC(=O)C=2C(=CC=C(C=2)[N+]([O-])=O)NC=2C(=CC(I)=CC=2)C)=C1 KLYXRBOQQVDCRR-UHFFFAOYSA-N 0.000 claims description 2
- FHXQAXYOKQYKHH-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=CC=C1C(O)=O FHXQAXYOKQYKHH-UHFFFAOYSA-N 0.000 claims description 2
- XLTVXGORWXCJNJ-UHFFFAOYSA-N 2-(4-iodoanilino)-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC=C(I)C=C1 XLTVXGORWXCJNJ-UHFFFAOYSA-N 0.000 claims description 2
- IKYHHUKKYADHCL-UHFFFAOYSA-N 3,4,5-trifluoro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(F)C=C1C(O)=O IKYHHUKKYADHCL-UHFFFAOYSA-N 0.000 claims description 2
- SXAYAMZOIRULRY-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-morpholin-4-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCN1CCOCC1 SXAYAMZOIRULRY-UHFFFAOYSA-N 0.000 claims description 2
- OSWADHCUFNBMDE-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-pyridin-4-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCC1=CC=NC=C1 OSWADHCUFNBMDE-UHFFFAOYSA-N 0.000 claims description 2
- HSRZYLYUHGKRQA-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCN1CCCC1 HSRZYLYUHGKRQA-UHFFFAOYSA-N 0.000 claims description 2
- UYUHIMXYEAWUTA-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(pyridin-4-ylmethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCC1=CC=NC=C1 UYUHIMXYEAWUTA-UHFFFAOYSA-N 0.000 claims description 2
- LEYZOHZNXYPUBL-UHFFFAOYSA-N 4-chloro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC(Cl)=CC=C1C(O)=O LEYZOHZNXYPUBL-UHFFFAOYSA-N 0.000 claims description 2
- GHJJMBQQZZBWJC-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C GHJJMBQQZZBWJC-UHFFFAOYSA-N 0.000 claims description 2
- HUNHDWQNBANZPB-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(2-morpholin-4-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCCN1CCOCC1 HUNHDWQNBANZPB-UHFFFAOYSA-N 0.000 claims description 2
- JPFLPYISXHNBBZ-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(2-phenylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCCC1=CC=CC=C1 JPFLPYISXHNBBZ-UHFFFAOYSA-N 0.000 claims description 2
- TXVFFQLHNCTHDG-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(2-pyridin-4-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCCC1=CC=NC=C1 TXVFFQLHNCTHDG-UHFFFAOYSA-N 0.000 claims description 2
- ALEXORMOTRNKGS-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCCN1CCCC1 ALEXORMOTRNKGS-UHFFFAOYSA-N 0.000 claims description 2
- KYPCIWQNEIGNMW-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(2h-tetrazol-5-yl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NC1=NN=NN1 KYPCIWQNEIGNMW-UHFFFAOYSA-N 0.000 claims description 2
- SQKWOEQAJIDRHG-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(pyridin-4-ylmethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCC1=CC=NC=C1 SQKWOEQAJIDRHG-UHFFFAOYSA-N 0.000 claims description 2
- HHSBHFSKYJRNAR-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C HHSBHFSKYJRNAR-UHFFFAOYSA-N 0.000 claims description 2
- WOHHWWLIRJXRJT-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-propylbenzamide Chemical compound CCCNC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C WOHHWWLIRJXRJT-UHFFFAOYSA-N 0.000 claims description 2
- COEXMYRMIABFRK-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(N)=O COEXMYRMIABFRK-UHFFFAOYSA-N 0.000 claims description 2
- YGSACSKOTDWEIY-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC(Br)=CC=C1NC1=CC=C(I)C=C1C YGSACSKOTDWEIY-UHFFFAOYSA-N 0.000 claims description 2
- IAVNIGIRNWGCLU-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-(2-piperidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCN1CCCCC1 IAVNIGIRNWGCLU-UHFFFAOYSA-N 0.000 claims description 2
- NJJDWJWIEWSECZ-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCN1CCCC1 NJJDWJWIEWSECZ-UHFFFAOYSA-N 0.000 claims description 2
- HIDZKFBLBMEGIG-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-(3-piperidin-1-ylpropyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCCN1CCCCC1 HIDZKFBLBMEGIG-UHFFFAOYSA-N 0.000 claims description 2
- MXCDWFRGCXEWHI-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-[(3-methylphenyl)methyl]benzamide Chemical compound CC1=CC=CC(CNC(=O)C=2C(=CC=C(Br)C=2)NC=2C(=CC(I)=CC=2)C)=C1 MXCDWFRGCXEWHI-UHFFFAOYSA-N 0.000 claims description 2
- GTXGFBQHXPMFRF-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(N)=O GTXGFBQHXPMFRF-UHFFFAOYSA-N 0.000 claims description 2
- BSFZRPNXKUHUAO-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(O)=O BSFZRPNXKUHUAO-UHFFFAOYSA-N 0.000 claims description 2
- SQGHOLDHMVSJEQ-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(pyridin-4-ylmethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NCC1=CC=NC=C1 SQGHOLDHMVSJEQ-UHFFFAOYSA-N 0.000 claims description 2
- PADIEEAWBNJBQS-UHFFFAOYSA-N 5-bromo-n-(3-hydroxypropyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCCO PADIEEAWBNJBQS-UHFFFAOYSA-N 0.000 claims description 2
- AZVJODFNVSECTP-UHFFFAOYSA-N 5-bromo-n-[2-(diethylamino)ethyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Br)=CC=C1NC1=CC=C(I)C=C1C AZVJODFNVSECTP-UHFFFAOYSA-N 0.000 claims description 2
- IVARVMGCQQJYCS-UHFFFAOYSA-N 5-bromo-n-[2-[di(propan-2-yl)amino]ethyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC(C)N(C(C)C)CCNC(=O)C1=CC(Br)=CC=C1NC1=CC=C(I)C=C1C IVARVMGCQQJYCS-UHFFFAOYSA-N 0.000 claims description 2
- YUKGGEUVPFOCFI-UHFFFAOYSA-N 5-bromo-n-[3-(dimethylamino)propyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CN(C)CCCNC(=O)C1=CC(Br)=CC=C1NC1=CC=C(I)C=C1C YUKGGEUVPFOCFI-UHFFFAOYSA-N 0.000 claims description 2
- GNQPYQRZLIRIAD-UHFFFAOYSA-N 5-bromo-n-cyclohexyl-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NC1CCCCC1 GNQPYQRZLIRIAD-UHFFFAOYSA-N 0.000 claims description 2
- LVSSVNULIKSVNX-UHFFFAOYSA-N 5-chloro-2-(4-iodo-2-methylanilino)-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC(Cl)=CC=C1NC1=CC=C(I)C=C1C LVSSVNULIKSVNX-UHFFFAOYSA-N 0.000 claims description 2
- UQFNVBACOUIFNY-UHFFFAOYSA-N 5-chloro-2-(4-iodo-2-methylanilino)-n-(2-piperidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NCCN1CCCCC1 UQFNVBACOUIFNY-UHFFFAOYSA-N 0.000 claims description 2
- RTCMPVBAZMDRHK-UHFFFAOYSA-N 5-chloro-2-(4-iodo-2-methylanilino)-n-[(3-methylphenyl)methyl]benzamide Chemical compound CC1=CC=CC(CNC(=O)C=2C(=CC=C(Cl)C=2)NC=2C(=CC(I)=CC=2)C)=C1 RTCMPVBAZMDRHK-UHFFFAOYSA-N 0.000 claims description 2
- IHNKPBIVPDAOMS-UHFFFAOYSA-N 5-chloro-n-(3-hydroxypropyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NCCCO IHNKPBIVPDAOMS-UHFFFAOYSA-N 0.000 claims description 2
- WPTQCTMJDFCZSI-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=CC=C1NC1=CC=C(I)C=C1C WPTQCTMJDFCZSI-UHFFFAOYSA-N 0.000 claims description 2
- TUWOHSIPLLUTFB-UHFFFAOYSA-N 5-chloro-n-[2-[di(propan-2-yl)amino]ethyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC(C)N(C(C)C)CCNC(=O)C1=CC(Cl)=CC=C1NC1=CC=C(I)C=C1C TUWOHSIPLLUTFB-UHFFFAOYSA-N 0.000 claims description 2
- GUGZLIXQNJDNQN-UHFFFAOYSA-N 5-chloro-n-[3-(diethylamino)propyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCN(CC)CCCNC(=O)C1=CC(Cl)=CC=C1NC1=CC=C(I)C=C1C GUGZLIXQNJDNQN-UHFFFAOYSA-N 0.000 claims description 2
- OQWXTWHGTZIWBE-UHFFFAOYSA-N 5-chloro-n-[3-(dimethylamino)propyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CN(C)CCCNC(=O)C1=CC(Cl)=CC=C1NC1=CC=C(I)C=C1C OQWXTWHGTZIWBE-UHFFFAOYSA-N 0.000 claims description 2
- YPPGTJWMYLGECO-UHFFFAOYSA-N 5-chloro-n-cyclohexyl-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NC1CCCCC1 YPPGTJWMYLGECO-UHFFFAOYSA-N 0.000 claims description 2
- TYGDKZJTFRTMAO-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-(2-piperidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCN1CCCCC1 TYGDKZJTFRTMAO-UHFFFAOYSA-N 0.000 claims description 2
- SFKIHCBPGXCYLE-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCN1CCCC1 SFKIHCBPGXCYLE-UHFFFAOYSA-N 0.000 claims description 2
- XTIXMUNFVWCJGM-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-(3-piperidin-1-ylpropyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCCN1CCCCC1 XTIXMUNFVWCJGM-UHFFFAOYSA-N 0.000 claims description 2
- ADRDDDZHIAHVOS-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-(pyridin-4-ylmethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCC1=CC=NC=C1 ADRDDDZHIAHVOS-UHFFFAOYSA-N 0.000 claims description 2
- BNECLIPSPRXTNW-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-[(3-methylphenyl)methyl]benzamide Chemical compound CC1=CC=CC(CNC(=O)C=2C(=CC=C(F)C=2)NC=2C(=CC(I)=CC=2)C)=C1 BNECLIPSPRXTNW-UHFFFAOYSA-N 0.000 claims description 2
- NDLMMYHLEMKNIS-UHFFFAOYSA-N 5-fluoro-n-(3-hydroxypropyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCCO NDLMMYHLEMKNIS-UHFFFAOYSA-N 0.000 claims description 2
- USDURDZZSHBDOA-UHFFFAOYSA-N 5-iodo-2-(4-iodo-2-methylanilino)-n-[(3-methylphenyl)methyl]benzamide Chemical compound CC1=CC=CC(CNC(=O)C=2C(=CC=C(I)C=2)NC=2C(=CC(I)=CC=2)C)=C1 USDURDZZSHBDOA-UHFFFAOYSA-N 0.000 claims description 2
- LOUSDJOLFFYIHT-UHFFFAOYSA-N 5-iodo-2-(4-iodo-2-methylanilino)-n-[(4-sulfamoylphenyl)methyl]benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NCC1=CC=C(S(N)(=O)=O)C=C1 LOUSDJOLFFYIHT-UHFFFAOYSA-N 0.000 claims description 2
- ISSKCCWEUYSNQW-UHFFFAOYSA-N 5-iodo-2-(4-iodo-2-methylanilino)-n-methyl-n-phenylbenzamide Chemical compound C=1C=CC=CC=1N(C)C(=O)C1=CC(I)=CC=C1NC1=CC=C(I)C=C1C ISSKCCWEUYSNQW-UHFFFAOYSA-N 0.000 claims description 2
- KOXXMRABYKWLII-UHFFFAOYSA-N 5-iodo-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(O)=O KOXXMRABYKWLII-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000006029 Cardiomegaly Diseases 0.000 claims description 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 206010019842 Hepatomegaly Diseases 0.000 claims description 2
- PNWJMZMIJSAVRR-UHFFFAOYSA-N [2-(4-iodo-2-methylanilino)-5-nitrophenyl]methanol Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1CO PNWJMZMIJSAVRR-UHFFFAOYSA-N 0.000 claims description 2
- QAFJIVFPYARMAT-UHFFFAOYSA-N [5-bromo-2-(4-iodo-2-methylanilino)phenyl]methanol Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1CO QAFJIVFPYARMAT-UHFFFAOYSA-N 0.000 claims description 2
- KARCBUCWSFRWNA-UHFFFAOYSA-N [5-chloro-2-(4-iodo-2-methylanilino)phenyl]methanol Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1CO KARCBUCWSFRWNA-UHFFFAOYSA-N 0.000 claims description 2
- SKMCJUSFAIWLJG-UHFFFAOYSA-N n,n-diethyl-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CCN(CC)C(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(I)C=C1C SKMCJUSFAIWLJG-UHFFFAOYSA-N 0.000 claims description 2
- PINUTQQQUYREAM-UHFFFAOYSA-N n,n-diethyl-4-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCN(CC)C(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C PINUTQQQUYREAM-UHFFFAOYSA-N 0.000 claims description 2
- DMGLLVWXKXWTIL-UHFFFAOYSA-N n-(3-hydroxypropyl)-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NCCCO DMGLLVWXKXWTIL-UHFFFAOYSA-N 0.000 claims description 2
- HDYUNAODPNRHCT-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-5-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(F)=CC=C1NC1=CC=C(I)C=C1C HDYUNAODPNRHCT-UHFFFAOYSA-N 0.000 claims description 2
- MFTVPZWSFTVKDW-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CN(C)CCCNC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1C MFTVPZWSFTVKDW-UHFFFAOYSA-N 0.000 claims description 2
- PMRYRJFGVUNXAW-UHFFFAOYSA-N n-benzyl-4-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCC1=CC=CC=C1 PMRYRJFGVUNXAW-UHFFFAOYSA-N 0.000 claims description 2
- QVEIDMMXXOMGHZ-UHFFFAOYSA-N n-butyl-4-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCCCNC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C QVEIDMMXXOMGHZ-UHFFFAOYSA-N 0.000 claims description 2
- ZHKTXUBWPSVDAP-UHFFFAOYSA-N n-cyclohexyl-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NC1CCCCC1 ZHKTXUBWPSVDAP-UHFFFAOYSA-N 0.000 claims description 2
- ZTMPSQKWWVAXQV-UHFFFAOYSA-N n-cyclohexyl-5-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NC1CCCCC1 ZTMPSQKWWVAXQV-UHFFFAOYSA-N 0.000 claims description 2
- FKURQLBTBBUUAQ-UHFFFAOYSA-N n-cyclohexyl-5-iodo-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NC1CCCCC1 FKURQLBTBBUUAQ-UHFFFAOYSA-N 0.000 claims description 2
- GNBCJLIYQMNLNA-UHFFFAOYSA-N n-cyclopropyl-5-iodo-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NC1CC1 GNBCJLIYQMNLNA-UHFFFAOYSA-N 0.000 claims description 2
- CDOZIVZPNPKUPY-UHFFFAOYSA-N n-ethyl-4-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCNC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C CDOZIVZPNPKUPY-UHFFFAOYSA-N 0.000 claims description 2
- LWWPTYNMVLDNII-UHFFFAOYSA-M sodium;5-chloro-2-(4-iodo-2-methylanilino)benzoate Chemical compound [Na+].CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C([O-])=O LWWPTYNMVLDNII-UHFFFAOYSA-M 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- VGCAUBADGNQYOE-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-5-nitrobenzoic acid 2-(4-bromo-2-methylanilino)-3,4-difluorobenzoic acid 2-(4-bromo-2-methylanilino)-4-fluorobenzoic acid Chemical compound BrC1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1F)F)C.BrC1=C(C=CC(=C1)I)NC1=C(C(=O)O)C=C(C=C1)[N+](=O)[O-].BrC1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1)F)C VGCAUBADGNQYOE-UHFFFAOYSA-N 0.000 claims 1
- MSOPPMSDGHOWLB-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-piperidin-1-ylethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCN1CCCCC1 MSOPPMSDGHOWLB-UHFFFAOYSA-N 0.000 claims 1
- RASWBMJSCOCCOP-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-n-[3-(dimethylamino)propyl]-3,4-difluorobenzamide Chemical compound CN(C)CCCNC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(Br)C=C1C RASWBMJSCOCCOP-UHFFFAOYSA-N 0.000 claims 1
- XKKPRURDQYWGIU-UHFFFAOYSA-N 3,4-difluoro-n-(3-hydroxypropyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCCCO XKKPRURDQYWGIU-UHFFFAOYSA-N 0.000 claims 1
- CIRRLTRICUDCSE-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-5-nitrobenzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=C([N+]([O-])=O)C=C1C(O)=O CIRRLTRICUDCSE-UHFFFAOYSA-N 0.000 claims 1
- VGSTYMDTHRWBEY-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)benzohydrazide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NN VGSTYMDTHRWBEY-UHFFFAOYSA-N 0.000 claims 1
- DWXSHLDPWGVUAY-UHFFFAOYSA-N 4-fluoro-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCCO DWXSHLDPWGVUAY-UHFFFAOYSA-N 0.000 claims 1
- PJMHNOKJJUERIL-UHFFFAOYSA-N 4-fluoro-n-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCCCN1CCN(CCO)CC1 PJMHNOKJJUERIL-UHFFFAOYSA-N 0.000 claims 1
- CXSHZTDJFXMXPL-UHFFFAOYSA-N 4-iodo-6-methyl-4-nitro-6-(2h-tetrazol-5-yl)cyclohex-2-en-1-amine Chemical compound N1=NNN=C1C1(C)CC(I)([N+]([O-])=O)C=CC1N CXSHZTDJFXMXPL-UHFFFAOYSA-N 0.000 claims 1
- JSROFQXNBQJWGD-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-morpholin-4-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NCCN1CCOCC1 JSROFQXNBQJWGD-UHFFFAOYSA-N 0.000 claims 1
- QTDDKGUPEPKNIP-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-piperidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NCCN1CCCCC1 QTDDKGUPEPKNIP-UHFFFAOYSA-N 0.000 claims 1
- LOWHNAGNDJCFSR-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-pyridin-4-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NCCC1=CC=NC=C1 LOWHNAGNDJCFSR-UHFFFAOYSA-N 0.000 claims 1
- RDSDFNHYHOTLTQ-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NCCN1CCCC1 RDSDFNHYHOTLTQ-UHFFFAOYSA-N 0.000 claims 1
- JETNCDYHKNDALF-UHFFFAOYSA-N 5-bromo-n-[3-(dimethylamino)propyl]-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CN(C)CCCNC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1C JETNCDYHKNDALF-UHFFFAOYSA-N 0.000 claims 1
- JREYCDFOVXBKQM-UHFFFAOYSA-N 5-bromo-n-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCCN1CCN(CCO)CC1 JREYCDFOVXBKQM-UHFFFAOYSA-N 0.000 claims 1
- CLAKDMJHMLECDQ-UHFFFAOYSA-N 5-chloro-n-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NCCCN1CCN(CCO)CC1 CLAKDMJHMLECDQ-UHFFFAOYSA-N 0.000 claims 1
- PPBHPHGQDGGSHX-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(O)=O PPBHPHGQDGGSHX-UHFFFAOYSA-N 0.000 claims 1
- 230000001028 anti-proliverative effect Effects 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- YXZHWOBVIDBYEI-UHFFFAOYSA-N methyl 2,3,5-trifluoro-6-(4-iodo-2-methylanilino)-4-(4-methylpiperazin-1-yl)benzoate;dihydrofluoride Chemical compound F.F.FC1=C(NC=2C(=CC(I)=CC=2)C)C(C(=O)OC)=C(F)C(F)=C1N1CCN(C)CC1 YXZHWOBVIDBYEI-UHFFFAOYSA-N 0.000 claims 1
- AZTURQUTRYVAEY-UHFFFAOYSA-N n-(2,3-dihydroxypropyl)-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NCC(O)CO AZTURQUTRYVAEY-UHFFFAOYSA-N 0.000 claims 1
- SXKAKDLNOMWWGH-UHFFFAOYSA-N n-[2-[bis(2-hydroxyethyl)amino]ethyl]-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NCCN(CCO)CCO SXKAKDLNOMWWGH-UHFFFAOYSA-N 0.000 claims 1
- QFICQLHYTPHHHZ-UHFFFAOYSA-N n-[2-[bis(2-hydroxyethyl)amino]ethyl]-5-bromo-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCN(CCO)CCO QFICQLHYTPHHHZ-UHFFFAOYSA-N 0.000 claims 1
- ABMFCKSENBKLRK-UHFFFAOYSA-N n-[2-[bis(2-hydroxyethyl)amino]ethyl]-5-chloro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NCCN(CCO)CCO ABMFCKSENBKLRK-UHFFFAOYSA-N 0.000 claims 1
- RESDNAOQJMJZLG-UHFFFAOYSA-N n-[2-[bis(2-hydroxyethyl)amino]ethyl]-5-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCN(CCO)CCO RESDNAOQJMJZLG-UHFFFAOYSA-N 0.000 claims 1
- XQLIVOYIWQHNST-UHFFFAOYSA-N n-[3-(diethylamino)-2-hydroxypropyl]-5-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCN(CC)CC(O)CNC(=O)C1=CC(F)=CC=C1NC1=CC=C(I)C=C1C XQLIVOYIWQHNST-UHFFFAOYSA-N 0.000 claims 1
- IKFPRHQBWHOCKH-UHFFFAOYSA-N n-[3-(diethylamino)propyl]-5-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCN(CC)CCCNC(=O)C1=CC(F)=CC=C1NC1=CC=C(I)C=C1C IKFPRHQBWHOCKH-UHFFFAOYSA-N 0.000 claims 1
- YNKVTTVVGYTRNM-UHFFFAOYSA-N n-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=CC=C1C(=O)NCCCN1CCN(CCO)CC1 YNKVTTVVGYTRNM-UHFFFAOYSA-N 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 108091054455 MAP kinase family Proteins 0.000 description 23
- 102000043136 MAP kinase family Human genes 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 108091000080 Phosphotransferase Proteins 0.000 description 16
- 102000020233 phosphotransferase Human genes 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 230000026731 phosphorylation Effects 0.000 description 12
- 238000006366 phosphorylation reaction Methods 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 239000005711 Benzoic acid Substances 0.000 description 11
- 230000004913 activation Effects 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 235000010233 benzoic acid Nutrition 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 102000016914 ras Proteins Human genes 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 150000002431 hydrogen Chemical group 0.000 description 8
- 238000011534 incubation Methods 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 5
- 229940124647 MEK inhibitor Drugs 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- ZKHQWZAMYRWXGA-KNYAHOBESA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] dihydroxyphosphoryl hydrogen phosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)O[32P](O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KNYAHOBESA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical class OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 238000000376 autoradiography Methods 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 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 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229910001629 magnesium chloride Inorganic materials 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 238000003345 scintillation counting Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 3
- MTTOQVVDHYZDHE-UHFFFAOYSA-N 5-(5-chloro-2-fluorophenyl)-2h-tetrazole Chemical compound FC1=CC=C(Cl)C=C1C1=NN=NN1 MTTOQVVDHYZDHE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 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 3
- 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 3
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 3
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 3
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 3
- 102000005720 Glutathione transferase Human genes 0.000 description 3
- 108010070675 Glutathione transferase Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 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 3
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 3
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000000453 Skin Neoplasms Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000003936 benzamides Chemical class 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000002297 mitogenic effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 201000000849 skin cancer Diseases 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 2
- MHWFUVYLWSTWJG-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1Cl MHWFUVYLWSTWJG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
- BGKLFAQCHHCZRZ-UHFFFAOYSA-N 4-iodo-2-methylaniline Chemical compound CC1=CC(I)=CC=C1N BGKLFAQCHHCZRZ-UHFFFAOYSA-N 0.000 description 2
- WDTUCEMLUHTMCB-UHFFFAOYSA-N 5-chloro-2-fluorobenzaldehyde Chemical compound FC1=CC=C(Cl)C=C1C=O WDTUCEMLUHTMCB-UHFFFAOYSA-N 0.000 description 2
- GJNJDELEHIGPKJ-UHFFFAOYSA-N 5-chloro-2-fluorobenzonitrile Chemical compound FC1=CC=C(Cl)C=C1C#N GJNJDELEHIGPKJ-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 description 2
- 101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 101150009249 MAP2 gene Proteins 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- 102000047918 Myelin Basic Human genes 0.000 description 2
- 101710107068 Myelin basic protein Proteins 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 239000012083 RIPA buffer Substances 0.000 description 2
- 239000012722 SDS sample buffer Substances 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940054066 benzamide antipsychotics Drugs 0.000 description 2
- 150000003938 benzyl alcohols Chemical class 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- YGOLWJMMEQRTQY-UHFFFAOYSA-N n-[(5-chloro-2-fluorophenyl)methylidene]hydroxylamine Chemical compound ON=CC1=CC(Cl)=CC=C1F YGOLWJMMEQRTQY-UHFFFAOYSA-N 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 1
- RJCGZNCCVKIBHO-UHFFFAOYSA-N 1-chloro-4-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1 RJCGZNCCVKIBHO-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- NJYBIFYEWYWYAN-UHFFFAOYSA-N 2,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1F NJYBIFYEWYWYAN-UHFFFAOYSA-N 0.000 description 1
- YUJPYTYVUMHXQW-UHFFFAOYSA-N 2-(2,6-difluoro-4-iodoanilino)-3,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(F)=C1NC1=C(F)C=C(I)C=C1F YUJPYTYVUMHXQW-UHFFFAOYSA-N 0.000 description 1
- JWRHFLYCIUDIQS-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1Br JWRHFLYCIUDIQS-UHFFFAOYSA-N 0.000 description 1
- QMALWSSCPZJMOO-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(I)C=C1Br QMALWSSCPZJMOO-UHFFFAOYSA-N 0.000 description 1
- MRYJQJQHGCPHON-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-3,4-difluoro-5-nitrobenzoic acid Chemical compound C1=CC(=C(C=C1I)Cl)NC2=C(C(=C(C=C2C(=O)O)[N+](=O)[O-])F)F MRYJQJQHGCPHON-UHFFFAOYSA-N 0.000 description 1
- MOFDFFZTBUKFBO-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1NC1=CC=C(I)C=C1Cl MOFDFFZTBUKFBO-UHFFFAOYSA-N 0.000 description 1
- LCKFFPXRGOMQPT-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(I)C=C1Cl LCKFFPXRGOMQPT-UHFFFAOYSA-N 0.000 description 1
- KIUBJCBWGNLTFG-UHFFFAOYSA-N 2-(2-fluoro-4-iodoanilino)-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(I)C=C1F KIUBJCBWGNLTFG-UHFFFAOYSA-N 0.000 description 1
- UPPHUQVTOWZROO-UHFFFAOYSA-N 2-(3-chloro-4-iodo-2-methylanilino)-4-fluorobenzoic acid Chemical compound CC1=C(Cl)C(I)=CC=C1NC1=CC(F)=CC=C1C(O)=O UPPHUQVTOWZROO-UHFFFAOYSA-N 0.000 description 1
- OKAIUFBLOQNKIS-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluorobenzoic acid Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(O)=O OKAIUFBLOQNKIS-UHFFFAOYSA-N 0.000 description 1
- DFYRJMXCUCOACA-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-4-fluorobenzoic acid Chemical compound CC1=CC(Br)=CC=C1NC1=CC(F)=CC=C1C(O)=O DFYRJMXCUCOACA-UHFFFAOYSA-N 0.000 description 1
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- DAHWLPNSVWRDFB-UHFFFAOYSA-N 2-chloro-6-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=CC(Cl)=C1C(O)=O DAHWLPNSVWRDFB-UHFFFAOYSA-N 0.000 description 1
- CZDVKBNPCLSXTF-UHFFFAOYSA-N 2-fluoro-6-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=CC(F)=C1C(O)=O CZDVKBNPCLSXTF-UHFFFAOYSA-N 0.000 description 1
- GKSQCZBTWKAFIV-UHFFFAOYSA-N 2-phenylethyl 2-(4-iodo-2-methylanilino)-5-nitrobenzoate Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)OCCC1=CC=CC=C1 GKSQCZBTWKAFIV-UHFFFAOYSA-N 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
- YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
- RLFNSOUBVMLCHS-UHFFFAOYSA-N 3-chloro-2-(2-chloro-4-iodoanilino)benzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1NC1=CC=C(I)C=C1Cl RLFNSOUBVMLCHS-UHFFFAOYSA-N 0.000 description 1
- HKDQXFITKMWGCA-UHFFFAOYSA-N 3-fluoro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C=CC=C1C(O)=O HKDQXFITKMWGCA-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000006192 3-phenylprop-2-enyl group Chemical group [H]\C(=C(\[H])C([H])([H])*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- IHJGXQRQHCDFJX-UHFFFAOYSA-N 4-amino-2-(2-chloro-4-iodoanilino)-3-fluoro-5-nitrobenzoic acid Chemical compound C1=C([N+]([O-])=O)C(N)=C(F)C(NC=2C(=CC(I)=CC=2)Cl)=C1C(O)=O IHJGXQRQHCDFJX-UHFFFAOYSA-N 0.000 description 1
- RBSKNOAECVHCJC-UHFFFAOYSA-N 4-iodo-2-methyl-n-[2-(2h-tetrazol-5-yl)phenyl]aniline Chemical compound CC1=CC(I)=CC=C1NC1=CC=CC=C1C1=NN=NN1 RBSKNOAECVHCJC-UHFFFAOYSA-N 0.000 description 1
- VLVCDUSVTXIWGW-UHFFFAOYSA-N 4-iodoaniline Chemical compound NC1=CC=C(I)C=C1 VLVCDUSVTXIWGW-UHFFFAOYSA-N 0.000 description 1
- WDCVVUHGOMOJNR-UHFFFAOYSA-N 4-methoxy-n-(4-methoxyphenyl)-3-nitrobenzamide Chemical compound C1=CC(OC)=CC=C1NC(=O)C1=CC=C(OC)C([N+]([O-])=O)=C1 WDCVVUHGOMOJNR-UHFFFAOYSA-N 0.000 description 1
- ZMAAJJJCLUAITF-UHFFFAOYSA-N 5-bromo-2-(2-chloro-4-iodoanilino)-3,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl ZMAAJJJCLUAITF-UHFFFAOYSA-N 0.000 description 1
- DESOLFCZYNVVHJ-UHFFFAOYSA-N 5-chloro-2-(4-iodo-2-methylanilino)-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NCCN1CCCC1 DESOLFCZYNVVHJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- 108030004793 Dual-specificity kinases Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 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 1
- XYZZKVRWGOWVGO-UHFFFAOYSA-N Glycerol-phosphate Chemical compound OP(O)(O)=O.OCC(O)CO XYZZKVRWGOWVGO-UHFFFAOYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 102000001702 Intracellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010068964 Intracellular Signaling Peptides and Proteins Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 239000012741 Laemmli sample buffer Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 101100247316 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) ras-1 gene Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 101100017604 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HOR7 gene Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 239000006180 TBST buffer Substances 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- PMMURAAUARKVCB-UHFFFAOYSA-N alpha-D-ara-dHexp Natural products OCC1OC(O)CC(O)C1O PMMURAAUARKVCB-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000002701 cell growth assay Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical group C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 108091022884 dihydropyrimidinase Proteins 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000667 effect on insulin Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000006379 fluoropyridyl group Chemical group 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- HAUKUGBTJXWQMF-UHFFFAOYSA-N lithium;propan-2-olate Chemical compound [Li+].CC(C)[O-] HAUKUGBTJXWQMF-UHFFFAOYSA-N 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- HVMSAZSBXQHNDL-UHFFFAOYSA-N n-(2,3-dihydroxypropyl)-4-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCC(O)CO HVMSAZSBXQHNDL-UHFFFAOYSA-N 0.000 description 1
- GSUQGEQHBNXARP-UHFFFAOYSA-N n-[2-[di(propan-2-yl)amino]ethyl]-5-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC(C)N(C(C)C)CCNC(=O)C1=CC(F)=CC=C1NC1=CC=C(I)C=C1C GSUQGEQHBNXARP-UHFFFAOYSA-N 0.000 description 1
- RYONWGDKFMCGQK-UHFFFAOYSA-N n-[3-(diethylamino)propyl]-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CCN(CC)CCCNC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(I)C=C1C RYONWGDKFMCGQK-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- UWBHMRBRLOJJAA-UHFFFAOYSA-N oxaluric acid Chemical compound NC(=O)NC(=O)C(O)=O UWBHMRBRLOJJAA-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000000704 physical effect Effects 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
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- QTDJRZSPOPELPU-UHFFFAOYSA-N s-(2-phenylethyl) 5-chloro-2-(4-iodo-2-methylanilino)benzenecarbothioate Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)SCCC1=CC=CC=C1 QTDJRZSPOPELPU-UHFFFAOYSA-N 0.000 description 1
- QCZYEGJADPODIL-UHFFFAOYSA-N s-(2-phenylethyl) 5-fluoro-2-(4-iodo-2-methylanilino)benzenecarbothioate Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)SCCC1=CC=CC=C1 QCZYEGJADPODIL-UHFFFAOYSA-N 0.000 description 1
- MZWWXGJDHZGDNB-UHFFFAOYSA-N s-benzyl 2-(4-iodo-2-methylanilino)-5-nitrobenzenecarbothioate Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)SCC1=CC=CC=C1 MZWWXGJDHZGDNB-UHFFFAOYSA-N 0.000 description 1
- NUSWDIDPAXABIZ-UHFFFAOYSA-N s-benzyl 5-bromo-2-(4-iodo-2-methylanilino)benzenecarbothioate Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)SCC1=CC=CC=C1 NUSWDIDPAXABIZ-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 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
- 125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/68—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
- C07C229/58—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position having the nitrogen atom of at least one of the amino groups further bound to a carbon atom of a six-membered aromatic ring, e.g. N-phenyl-anthranilic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/36—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/38—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
- C07C311/44—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/28—Nitrogen atoms
- C07D295/32—Nitrogen atoms acylated with carboxylic or carbonic acids, or their nitrogen or sulfur analogues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5143397P | 1997-07-01 | 1997-07-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP980369A2 true HRP980369A2 (en) | 1999-04-30 |
Family
ID=21971291
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR60/051,433A HRP980369A2 (en) | 1997-07-01 | 1998-06-30 | 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP0993437B1 (es) |
JP (1) | JP2002509536A (es) |
KR (1) | KR20010014360A (es) |
AR (1) | AR016119A1 (es) |
AT (1) | ATE344791T1 (es) |
AU (1) | AU756586C (es) |
BR (1) | BR9810385A (es) |
CA (1) | CA2290509A1 (es) |
DE (1) | DE69836378T2 (es) |
ES (1) | ES2274572T3 (es) |
HR (1) | HRP980369A2 (es) |
NZ (1) | NZ501277A (es) |
PE (1) | PE98099A1 (es) |
TW (1) | TWI221831B (es) |
UY (1) | UY25075A1 (es) |
WO (1) | WO1999001421A1 (es) |
ZA (1) | ZA985726B (es) |
Families Citing this family (92)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6506798B1 (en) | 1997-07-01 | 2003-01-14 | Warner-Lambert Company | 4-Arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective MEK inhibitors |
US7354894B2 (en) | 1998-08-18 | 2008-04-08 | The Regents Of The University Of California | Preventing airway mucus production by administration of EGF-R antagonists |
US6846799B1 (en) | 1998-08-18 | 2005-01-25 | The Regents Of The University Of California | Preventing airway mucus production by administration of EGF-R antagonists |
JP2002532414A (ja) * | 1998-12-15 | 2002-10-02 | ワーナー−ランバート・カンパニー | 移植片拒絶反応を防止するためのmek阻害剤の使用 |
HUP0104933A3 (en) * | 1999-01-07 | 2003-12-29 | Warner Lambert Co | Antiviral method using mek inhibitors |
CN1149204C (zh) | 1999-01-13 | 2004-05-12 | 沃尼尔·朗伯公司 | 1-杂环取代的二芳基胺 |
CA2348236A1 (en) * | 1999-01-13 | 2000-07-20 | Stephen Douglas Barrett | 4-arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective mek inhibitors |
WO2000050398A2 (en) | 1999-02-24 | 2000-08-31 | F. Hoffmann-La Roche Ag | Phenyl- and pyridinyl derivatives as neurokinin 1 antagonists |
GB9910580D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910579D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
AU5785900A (en) * | 1999-07-16 | 2001-02-05 | Warner-Lambert Company | Method for treating chronic pain using mek inhibitors |
TR200200082T2 (tr) * | 1999-07-16 | 2002-04-22 | Warner-Lambert Company | MEK inhibitörleri kullanılarak kronik ağrının tedavi edilmesi. |
HUP0202180A3 (en) * | 1999-07-16 | 2004-10-28 | Warner Lambert Co | Method for treating chronic pain using mek inhibitors |
US7345051B2 (en) | 2000-01-31 | 2008-03-18 | Genaera Corporation | Mucin synthesis inhibitors |
WO2001054685A1 (en) * | 2000-01-31 | 2001-08-02 | Genaera Corporation | Mucin synthesis inhibitors |
GB0002740D0 (en) * | 2000-02-07 | 2000-03-29 | Novartis Ag | Organic compounds |
US7001905B2 (en) | 2000-03-15 | 2006-02-21 | Warner-Lambert Company | Substituted diarylamines as MEK inhibitors |
JP2003527379A (ja) * | 2000-03-15 | 2003-09-16 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | Mex阻害物質としての5−アミド置換ジアリールアミン類 |
DE10017480A1 (de) * | 2000-04-07 | 2001-10-11 | Transmit Technologietransfer | Verwendung von Substanzen, die als MEK Inhibitor wirken, zur Herstellung eines Arneimittels gegen DNA- und RNA-Viren |
US6964982B2 (en) | 2000-04-20 | 2005-11-15 | Neurotech Co., Ltd. | Compounds, compositions and methods for preventing neurodegeneration in acute and chronic injuries in the central nervous system |
DK1301472T3 (da) | 2000-07-19 | 2014-04-07 | Warner Lambert Co | Oxygenerede estere af 4-iod-phenylamino-benzhydroxamsyrer |
YU14303A (sh) * | 2000-08-25 | 2006-08-17 | Warner Lambert Company Llc. | Postupak pripremanja n-aril antranilnih kiselina i njihovih derivata |
EP1337513A1 (en) | 2000-11-02 | 2003-08-27 | AstraZeneca AB | 4-substituted quinolines as antitumor agents |
US7067532B2 (en) | 2000-11-02 | 2006-06-27 | Astrazeneca | Substituted quinolines as antitumor agents |
IL149462A0 (en) * | 2001-05-09 | 2002-11-10 | Warner Lambert Co | Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor |
DOP2003000556A (es) | 2002-01-23 | 2003-10-31 | Warner Lambert Co | Esteres hidroxamato de acido n-(4-fenil-sustituido)-antranilico. |
JP2005515253A (ja) | 2002-01-23 | 2005-05-26 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | N−(4−置換フェニル)−アントラニル酸ヒドロキサメートエステル |
KR100984613B1 (ko) | 2002-03-13 | 2010-09-30 | 어레이 바이오파마 인크. | Mek 억제제로서의 n3 알킬화 벤즈이미다졸 유도체 |
US7235537B2 (en) | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
US7012100B1 (en) | 2002-06-04 | 2006-03-14 | Avolix Pharmaceuticals, Inc. | Cell migration inhibiting compositions and methods and compositions for treating cancer |
CN1309703C (zh) | 2002-06-19 | 2007-04-11 | 纽若泰克有限公司 | 四氟苄基衍生物及含有其成分的用于治疗和预防中枢神经系统的急慢性神经变性疾病的药物组合物 |
US7632866B2 (en) | 2002-10-21 | 2009-12-15 | Ramot At Tel Aviv University | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators |
AU2003272068A1 (en) * | 2002-10-21 | 2004-05-04 | Ramot At Tel Aviv University Ltd. | Derivatives of n-phenylanthranilic acid and 2-benzimidazolon as potassium channel and/or cortical neuron activity modulators |
WO2005000818A1 (en) * | 2003-06-27 | 2005-01-06 | Warner-Lambert Company Llc | 5-substituted-4-`(substituted phenyl)!amino!-2-pyridone deviatives for use as mek inhibitors |
US7144907B2 (en) | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
US7538120B2 (en) | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
NZ546011A (en) | 2003-10-21 | 2009-09-25 | Warner Lambert Co | Polymorphic form of N-[(R)-2,3-dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-benzamide |
US7732616B2 (en) | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
EP1689387B1 (en) | 2003-11-19 | 2011-09-14 | Array Biopharma, Inc. | Bicyclic inhibitors of mek and methods of synthesis thereof |
US7517994B2 (en) | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
RU2006121990A (ru) | 2003-11-21 | 2007-12-27 | Эррэй Биофарма Инк. (Us) | Ингибиторы протеинкиназ акт |
SE0401969D0 (sv) * | 2004-08-02 | 2004-08-02 | Astrazeneca Ab | Piperidine derivatives |
CN101065358B (zh) | 2004-10-20 | 2015-03-11 | 默克雪兰诺有限公司 | 3-芳基氨基吡啶衍生物 |
AU2005308956A1 (en) * | 2004-11-24 | 2006-06-01 | Merck Serono Sa | Novel 4-arylamino pyridone derivatives as MEK inhibitors for the treatment of hyperproliferative disorders |
ES2330872T3 (es) * | 2004-12-01 | 2009-12-16 | Merck Serono Sa | Derivados de (1,2,4)triazolo(4,3-a)piridina para el tratamiento de enfermedades hiperproliferativas. |
DK1860098T3 (da) * | 2005-03-16 | 2012-12-17 | Toyama Chemical Co Ltd | Nyt anthranilsyrderivat eller salt deraf |
ES2405785T3 (es) | 2005-05-18 | 2013-06-03 | Array Biopharma Inc. | Inhibidores heterocíclicos de MEK y métodos de uso de los mismos |
WO2006126846A1 (en) * | 2005-05-25 | 2006-11-30 | Choongwae Pharma Corporation | Process of preparation of substituted tetrafluorobenzylaniline compound and its pharmaceutically approved salts |
AU2013203939B2 (en) * | 2005-10-07 | 2015-08-13 | Exelixis, Inc. | Azetidines as MEK inhibitors for the treatment of proliferative diseases |
AU2012261703B2 (en) * | 2005-10-07 | 2015-08-13 | Exelixis, Inc. | Azetidines as MEK inhibitors for the treatment of proliferative diseases |
AU2015255183C1 (en) * | 2005-10-07 | 2017-10-05 | Exelixis, Inc | Azetidines as MEK inhibitors for the treatment of proliferative diseases |
BRPI0617165B1 (pt) | 2005-10-07 | 2023-10-03 | Exelixis Inc | Compostos inibidores mek, composições farmacêuticas que os contem e métodos de uso dos mesmos |
GB0601962D0 (en) | 2006-01-31 | 2006-03-15 | Ucb Sa | Therapeutic agents |
CN101511842B (zh) | 2006-07-06 | 2012-10-31 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的二氢呋喃并嘧啶 |
US8063050B2 (en) | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
AU2007269052B2 (en) | 2006-07-06 | 2014-10-23 | Array Biopharma Inc. | Cyclopenta [D] pyrimidines as AKT protein kinase inhibitors |
DK2054418T3 (da) | 2006-07-06 | 2012-02-27 | Array Biopharma Inc | Dihydrothieno-pyrimidiner som AKT-proteinkinase-inhibitorer |
EP2056829B9 (en) * | 2006-08-16 | 2012-09-26 | Exelixis, Inc. | Using pi3k and mek modulators in treatments of cancer |
KR20090071666A (ko) | 2006-10-23 | 2009-07-01 | 다케다 야쿠힌 고교 가부시키가이샤 | Mapk/erk 키나아제 억제제 |
CA2671982C (en) | 2006-12-14 | 2016-01-26 | Exelixis, Inc. | Methods of using mek inhibitors |
ES2533557T3 (es) | 2007-07-05 | 2015-04-13 | Array Biopharma, Inc. | Pirimidil ciclopentanos como inhibidores de proteína cinasa AKT |
US9409886B2 (en) | 2007-07-05 | 2016-08-09 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
KR20150089099A (ko) | 2007-07-05 | 2015-08-04 | 어레이 바이오파마 인크. | Akt 단백질 키나제 억제제로서의 피리미딜 시클로펜탄 |
US8846683B2 (en) | 2007-07-05 | 2014-09-30 | Array Biopharma, Inc. | Pyrimidyl cyclopentanes as Akt protein kinase inhibitors |
CN101868443A (zh) | 2007-09-20 | 2010-10-20 | 特拉维夫大学拉莫特有限公司 | N-苯基邻氨基苯甲酸衍生物及其用途 |
WO2009037705A2 (en) * | 2007-09-20 | 2009-03-26 | Ramot At Tel Aviv University Ltd. | Esters of n-phenylanthranilic acid for use in the treatment of cancer and inflammation |
KR100852962B1 (ko) | 2007-11-12 | 2008-08-20 | 주식회사 뉴로테크 | 2-하이드록시-5-페닐알킬아미노벤조산 유도체 및 이의 염의제조방법 |
NZ586346A (en) | 2008-01-09 | 2012-02-24 | Array Biopharma Inc | Hydroxylated pyrimidyl cyclopentanes as akt protein kinase inhibitors |
US8853216B2 (en) | 2008-01-09 | 2014-10-07 | Array Biopharma, Inc. | Hydroxylated pyrimidyl cyclopentane as AKT protein kinase inhibitor |
GB0813403D0 (en) * | 2008-07-22 | 2008-08-27 | Lectus Therapeutics Ltd | Potassium ion channel modulators & uses thereof |
MX2011001127A (es) | 2008-08-04 | 2011-03-21 | Merck Patent Gmbh | Compuestos novedosos de fenilamino-isonicotinamida. |
ES2399384T3 (es) | 2008-11-10 | 2013-04-01 | Bayer Schering Pharma Ag | Sulfonamido fenoxibenzamidas sustituidas |
US9084781B2 (en) | 2008-12-10 | 2015-07-21 | Novartis Ag | MEK mutations conferring resistance to MEK inhibitors |
JP2013508320A (ja) | 2009-10-21 | 2013-03-07 | バイエル・ファルマ・アクチェンゲゼルシャフト | 置換されたハロフェノキシベンズアミド誘導体 |
JP2013508318A (ja) | 2009-10-21 | 2013-03-07 | バイエル・ファルマ・アクチェンゲゼルシャフト | 置換されたベンゾスルホンアミド誘導体 |
CA2777430A1 (en) | 2009-10-21 | 2011-04-28 | Bayer Pharma Aktiengesellschaft | Substituted benzosulphonamides |
BR112012021411A2 (pt) | 2010-02-25 | 2017-04-18 | Dana Farber Cancer Inst Inc | mutações braf que conferem resistência a inibidores braf. |
ES2714875T3 (es) | 2010-03-09 | 2019-05-30 | Dana Farber Cancer Inst Inc | Métodos de diagnóstico y tratamiento del cáncer en pacientes que presentan o desarrollan resistencia a una primera terapia del cáncer |
EP2632899A1 (en) | 2010-10-29 | 2013-09-04 | Bayer Intellectual Property GmbH | Substituted phenoxypyridines |
CN103841976A (zh) | 2011-04-01 | 2014-06-04 | 基因泰克公司 | Akt和mek抑制剂化合物的组合及其使用方法 |
CN104586861A (zh) | 2011-04-01 | 2015-05-06 | 基因泰克公司 | Akt抑制剂化合物和阿比特龙的组合及使用方法 |
CN103204827B (zh) | 2012-01-17 | 2014-12-03 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的苯并噻二唑化合物及其制备方法和用途 |
CN102617383A (zh) * | 2012-03-20 | 2012-08-01 | 横店集团家园化工有限公司 | 索法地尔晶型、制备方法及包含索法地尔晶体的无菌粉末 |
WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
SG11201407842TA (en) * | 2012-05-30 | 2014-12-30 | Merck Patent Gmbh | Solid state forms of n-((s)-2,3-dihydroxy-propyl)-3-(2-fluoro-4-iodo-phenylamino)-isonicotinamide |
GEP201706690B (en) | 2012-10-12 | 2017-06-26 | Exelixis Inc | Novel process for making compounds for use in treatment of cancer |
AU2014318748B2 (en) * | 2013-09-11 | 2019-02-28 | Duquesne University Of The Holy Ghost | Novel anthranilic amides and the use thereof |
EP3204516B1 (en) | 2014-10-06 | 2023-04-26 | Dana-Farber Cancer Institute, Inc. | Angiopoietin-2 biomarkers predictive of anti-immune checkpoint response |
MA41866A (fr) | 2015-03-31 | 2018-02-06 | Massachusetts Gen Hospital | Molécules à auto-assemblage pour l'administration ciblée de médicaments |
WO2020106306A1 (en) | 2018-11-20 | 2020-05-28 | Nflection Therapeutics, Inc. | Cyanoaryl-aniline compounds for treatment of dermal disorders |
CA3120351A1 (en) * | 2018-11-20 | 2020-05-28 | Nflection Therapeutics, Inc. | Aryl-aniline and heteroaryl-aniline compounds for treatment of skin cancers |
TW202342018A (zh) | 2022-03-04 | 2023-11-01 | 美商奇奈特生物製藥公司 | Mek激酶抑制劑 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2077249A (en) * | 1934-06-06 | 1937-04-13 | Winthrop Chem Co Inc | Basically substituted acridine compounds |
US5525625A (en) * | 1995-01-24 | 1996-06-11 | Warner-Lambert Company | 2-(2-Amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran for treating proliferative disorders |
AU5610398A (en) * | 1997-02-28 | 1998-09-18 | Warner-Lambert Company | Method of treating or preventing septic shock by administering a mek inhibitor |
-
1998
- 1998-06-24 AT AT98932829T patent/ATE344791T1/de not_active IP Right Cessation
- 1998-06-24 BR BR9810385-7A patent/BR9810385A/pt not_active Application Discontinuation
- 1998-06-24 AU AU82626/98A patent/AU756586C/en not_active Ceased
- 1998-06-24 JP JP50722799A patent/JP2002509536A/ja not_active Withdrawn
- 1998-06-24 WO PCT/US1998/013105 patent/WO1999001421A1/en active IP Right Grant
- 1998-06-24 NZ NZ501277A patent/NZ501277A/xx unknown
- 1998-06-24 CA CA002290509A patent/CA2290509A1/en not_active Abandoned
- 1998-06-24 EP EP98932829A patent/EP0993437B1/en not_active Expired - Lifetime
- 1998-06-24 ES ES98932829T patent/ES2274572T3/es not_active Expired - Lifetime
- 1998-06-24 DE DE69836378T patent/DE69836378T2/de not_active Expired - Fee Related
- 1998-06-24 KR KR1019997012517A patent/KR20010014360A/ko not_active Application Discontinuation
- 1998-06-25 TW TW087110251A patent/TWI221831B/zh not_active IP Right Cessation
- 1998-06-30 AR ARP980103164A patent/AR016119A1/es unknown
- 1998-06-30 ZA ZA985726A patent/ZA985726B/xx unknown
- 1998-06-30 UY UY25075A patent/UY25075A1/es not_active Application Discontinuation
- 1998-06-30 PE PE1998000580A patent/PE98099A1/es not_active Application Discontinuation
- 1998-06-30 HR HR60/051,433A patent/HRP980369A2/hr not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
TWI221831B (en) | 2004-10-11 |
AR016119A1 (es) | 2001-06-20 |
DE69836378T2 (de) | 2007-10-11 |
ZA985726B (en) | 1999-01-27 |
ES2274572T3 (es) | 2007-05-16 |
PE98099A1 (es) | 1999-11-05 |
UY25075A1 (es) | 1998-12-01 |
AU756586B2 (en) | 2003-01-16 |
BR9810385A (pt) | 2000-09-05 |
NZ501277A (en) | 2002-12-20 |
DE69836378D1 (de) | 2006-12-21 |
ATE344791T1 (de) | 2006-11-15 |
EP0993437B1 (en) | 2006-11-08 |
WO1999001421A1 (en) | 1999-01-14 |
KR20010014360A (ko) | 2001-02-26 |
AU756586C (en) | 2004-01-29 |
AU8262698A (en) | 1999-01-25 |
CA2290509A1 (en) | 1999-01-14 |
EP0993437A1 (en) | 2000-04-19 |
JP2002509536A (ja) | 2002-03-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP980369A2 (en) | 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives | |
US6310060B1 (en) | 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as MEK inhibitors | |
AU776788B2 (en) | Treatment of arthritis with MEK inhibitors | |
HRP980368A2 (en) | 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives | |
JP6178777B2 (ja) | ネクロトーシスの小分子阻害剤 | |
US6251943B1 (en) | Method of treating or preventing septic shock by administering a MEK inhibitor | |
OA11733A (en) | Combination chemotherapy. | |
CN106432137B (zh) | 组蛋白乙酰转移酶调节剂和其用途 | |
US20160297748A1 (en) | Compounds, compositions, and methods for modulating ferroptosis and treating excitotoxic disorders | |
WO2009053808A2 (en) | Histone deacetylase inhibitors | |
BR112013000783A2 (pt) | derivados arilamídicos tendo propriedades antiandrogênicas | |
CA2362259A1 (en) | Antizyme modulators and their use | |
Villa et al. | Efficacy of novel acridine derivatives in the inhibition of hPrP90-231 prion protein fragment toxicity | |
CZ200283A3 (cs) | Aminobenzofenony jako inhibitory IL-1beta a TNF-alfa | |
JP2012501344A (ja) | アミロイド症を治療する組成物及び方法 | |
MXPA99010556A (es) | Derivados de acido benzoico 2-(4-bromo o 4-yodofenilamino) y su uso como inhibidores de mek | |
Nian et al. | Synthesis and Biological Evaluation of N-(5-(2, 5-dimethyl-phenoxy)-2, 2-dimethylpentyl)-benzamide Derivatives as Novel Farnesoid X Receptor (FXR) Antagonist | |
Yu et al. | Structure–activity relationship studies on Pd176252 derivatives leading to discovery of novel GRP receptor antagonist with potent anticancer activity | |
MXPA99010649A (es) | Derivados del acido 4-bromoó4-yodo fenilamino benzihidroxamico y su uso como inhibidores de mek | |
MXPA01005476A (es) | Quimioterapia de combinacion | |
AU3132700A (en) | Slective beta3 adrenergic agonists |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A1OB | Publication of a patent application | ||
AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
ODBI | Application refused |