NZ522551A - Substituted styryl benzylsulfones for treating cancer and other proliferative diseases - Google Patents
Substituted styryl benzylsulfones for treating cancer and other proliferative diseasesInfo
- Publication number
- NZ522551A NZ522551A NZ522551A NZ52255101A NZ522551A NZ 522551 A NZ522551 A NZ 522551A NZ 522551 A NZ522551 A NZ 522551A NZ 52255101 A NZ52255101 A NZ 52255101A NZ 522551 A NZ522551 A NZ 522551A
- Authority
- NZ
- New Zealand
- Prior art keywords
- alkoxy
- compound according
- halogen
- hydrogen
- group
- Prior art date
Links
- -1 styryl benzylsulfones Chemical class 0.000 title claims abstract description 217
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 29
- 206010028980 Neoplasm Diseases 0.000 title claims description 28
- 201000011510 cancer Diseases 0.000 title claims description 26
- 230000002062 proliferating effect Effects 0.000 title claims description 19
- 201000010099 disease Diseases 0.000 title claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 170
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 144
- 150000002367 halogens Chemical class 0.000 claims abstract description 142
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 115
- 239000001257 hydrogen Substances 0.000 claims abstract description 115
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 110
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 105
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims abstract description 91
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims abstract description 90
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 89
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 87
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 85
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 83
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 275
- 238000000034 method Methods 0.000 claims description 89
- 239000003937 drug carrier Substances 0.000 claims description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims description 36
- 210000004027 cell Anatomy 0.000 claims description 35
- 210000004881 tumor cell Anatomy 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 16
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 12
- 206010016654 Fibrosis Diseases 0.000 claims description 12
- 230000006907 apoptotic process Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 208000016738 bone Paget disease Diseases 0.000 claims description 6
- 208000011803 breast fibrocystic disease Diseases 0.000 claims description 6
- 230000007882 cirrhosis Effects 0.000 claims description 6
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 6
- 230000001939 inductive effect Effects 0.000 claims description 6
- 208000011379 keloid formation Diseases 0.000 claims description 6
- 208000037803 restenosis Diseases 0.000 claims description 6
- 208000009905 Neurofibromatoses Diseases 0.000 claims description 5
- 210000000481 breast Anatomy 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 201000004931 neurofibromatosis Diseases 0.000 claims description 5
- 230000003287 optical effect Effects 0.000 claims description 5
- 230000000750 progressive effect Effects 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 claims description 5
- 230000002611 ovarian Effects 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- SBSLPPMPINEXNI-YDWXAUTNSA-N 1,2,3,4,5-pentafluoro-6-[(e)-3-(4-fluorophenyl)-1-[(e)-3-(4-fluorophenyl)-1-(2,3,4,5,6-pentafluorophenyl)prop-2-enyl]sulfonylprop-2-enyl]benzene Chemical compound C1=CC(F)=CC=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C=CC(F)=CC=1)C=1C(=C(F)C(F)=C(F)C=1F)F)C1=C(F)C(F)=C(F)C(F)=C1F SBSLPPMPINEXNI-YDWXAUTNSA-N 0.000 claims description 2
- JYQVQRVNPTWWPZ-WGDLNXRISA-N 1,2,3,4,5-pentafluoro-6-[(e)-3-(4-fluorophenyl)-3-[(e)-1-(4-fluorophenyl)-3-(2,3,4,5,6-pentafluorophenyl)prop-2-enyl]sulfonylprop-1-enyl]benzene Chemical compound C1=CC(F)=CC=C1C(S(=O)(=O)C(\C=C\C=1C(=C(F)C(F)=C(F)C=1F)F)C=1C=CC(F)=CC=1)\C=C\C1=C(F)C(F)=C(F)C(F)=C1F JYQVQRVNPTWWPZ-WGDLNXRISA-N 0.000 claims description 2
- ZBFGDONTPUMMDC-WGDLNXRISA-N 1,2,3,4,5-pentafluoro-6-[(e)-3-(4-iodophenyl)-3-[(e)-1-(4-iodophenyl)-3-(2,3,4,5,6-pentafluorophenyl)prop-2-enyl]sulfonylprop-1-enyl]benzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=C(F)C(F)=C(F)C=1F)F)C=1C=CC(I)=CC=1)C1=CC=C(I)C=C1 ZBFGDONTPUMMDC-WGDLNXRISA-N 0.000 claims description 2
- LSQPHWBCMFQPAP-XPWSMXQVSA-N 1,3,5-trimethoxy-2-[(e)-3-(4-methoxyphenyl)-3-[(e)-1-(4-methoxyphenyl)-3-(2,4,6-trimethoxyphenyl)prop-2-enyl]sulfonylprop-1-enyl]benzene Chemical compound C1=CC(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C(=CC(OC)=CC=1OC)OC)C=1C=CC(OC)=CC=1)\C=C\C1=C(OC)C=C(OC)C=C1OC LSQPHWBCMFQPAP-XPWSMXQVSA-N 0.000 claims description 2
- PZGCQHVZLVMFTO-FCXRPNKRSA-N 1-[(e)-3-(3,4-dichlorophenyl)-3-[(e)-1-(3,4-dichlorophenyl)-3-(2,3,4,5,6-pentafluorophenyl)prop-2-enyl]sulfonylprop-1-enyl]-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=C(F)C(F)=C(F)C=1F)F)C=1C=C(Cl)C(Cl)=CC=1)C1=CC=C(Cl)C(Cl)=C1 PZGCQHVZLVMFTO-FCXRPNKRSA-N 0.000 claims description 2
- YLDNMXSNYYBDFG-YDWXAUTNSA-N 1-[(e)-3-(4-bromophenyl)-1-[(e)-3-(4-bromophenyl)-1-(2,3,4,5,6-pentafluorophenyl)prop-2-enyl]sulfonylprop-2-enyl]-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1C(S(=O)(=O)C(\C=C\C=1C=CC(Br)=CC=1)C=1C(=C(F)C(F)=C(F)C=1F)F)\C=C\C1=CC=C(Br)C=C1 YLDNMXSNYYBDFG-YDWXAUTNSA-N 0.000 claims description 2
- BZTPAQNCKKWIPD-WGDLNXRISA-N 1-[(e)-3-(4-bromophenyl)-3-[(e)-1-(4-bromophenyl)-3-(2,3,4,5,6-pentafluorophenyl)prop-2-enyl]sulfonylprop-1-enyl]-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=C(F)C(F)=C(F)C=1F)F)C=1C=CC(Br)=CC=1)C1=CC=C(Br)C=C1 BZTPAQNCKKWIPD-WGDLNXRISA-N 0.000 claims description 2
- PBMCWLMEWFGPBX-ZPUQHVIOSA-N 1-[(e)-3-[(e)-1,3-bis(2,3,4,5,6-pentafluorophenyl)prop-2-enyl]sulfonyl-3-(2,3,4,5,6-pentafluorophenyl)prop-1-enyl]-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=C(F)C(F)=C(F)C=1F)F)C=1C(=C(F)C(F)=C(F)C=1F)F)C1=C(F)C(F)=C(F)C(F)=C1F PBMCWLMEWFGPBX-ZPUQHVIOSA-N 0.000 claims description 2
- UYBARLRUHOODMT-JYFOCSDGSA-N 1-[(e)-3-[(e)-3-(4,5-dimethoxy-2-nitrophenyl)-1-(4-methoxyphenyl)prop-2-enyl]sulfonyl-3-(4-methoxyphenyl)prop-1-enyl]-4,5-dimethoxy-2-nitrobenzene Chemical compound C1=CC(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C(=CC(OC)=C(OC)C=1)[N+]([O-])=O)C=1C=CC(OC)=CC=1)\C=C\C1=CC(OC)=C(OC)C=C1[N+]([O-])=O UYBARLRUHOODMT-JYFOCSDGSA-N 0.000 claims description 2
- GMGWSYNUDNAELW-WXUKJITCSA-N 2-[(e)-3-(4-bromophenyl)-3-[(e)-1-(4-bromophenyl)-3-(4-fluoro-2,6-dimethoxyphenyl)prop-2-enyl]sulfonylprop-1-enyl]-5-fluoro-1,3-dimethoxybenzene Chemical compound COC1=CC(F)=CC(OC)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=CC(F)=CC=1OC)OC)C=1C=CC(Br)=CC=1)C1=CC=C(Br)C=C1 GMGWSYNUDNAELW-WXUKJITCSA-N 0.000 claims description 2
- VHWWYXCXNRDABI-WXUKJITCSA-N 2-[(e)-3-(4-chlorophenyl)-3-[(e)-1-(4-chlorophenyl)-3-(4-fluoro-2,6-dimethoxyphenyl)prop-2-enyl]sulfonylprop-1-enyl]-5-fluoro-1,3-dimethoxybenzene Chemical compound COC1=CC(F)=CC(OC)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=CC(F)=CC=1OC)OC)C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 VHWWYXCXNRDABI-WXUKJITCSA-N 0.000 claims description 2
- HOPUNXURSBBUQQ-YTEMWHBBSA-N 2-[(e)-3-[(e)-3-(2-hydroxy-4,6-dimethoxyphenyl)-1-(4-methoxyphenyl)prop-2-enyl]sulfonyl-3-(4-methoxyphenyl)prop-1-enyl]-3,5-dimethoxyphenol Chemical compound C1=CC(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C(=CC(OC)=CC=1O)OC)C=1C=CC(OC)=CC=1)\C=C\C1=C(O)C=C(OC)C=C1OC HOPUNXURSBBUQQ-YTEMWHBBSA-N 0.000 claims description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 claims description 2
- 230000007717 exclusion Effects 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- VILMUCRZVVVJCA-UHFFFAOYSA-M sodium glycolate Chemical compound [Na+].OCC([O-])=O VILMUCRZVVVJCA-UHFFFAOYSA-M 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- UQVKZNNCIHJZLS-UHFFFAOYSA-N PhIP Chemical compound C1=C2N(C)C(N)=NC2=NC=C1C1=CC=CC=C1 UQVKZNNCIHJZLS-UHFFFAOYSA-N 0.000 claims 12
- 208000003174 Brain Neoplasms Diseases 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 230000001590 oxidative effect Effects 0.000 claims 2
- QQVYMEUZEPKQKA-UHFFFAOYSA-N 1,2,3,4,5-pentafluoro-6-[(2,3,4,5,6-pentafluorophenyl)methylsulfonylmethyl]benzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1CS(=O)(=O)CC1=C(F)C(F)=C(F)C(F)=C1F QQVYMEUZEPKQKA-UHFFFAOYSA-N 0.000 claims 1
- YFQFBQIGRJQFFS-BGPOSVGRSA-N 1,2,3-trifluoro-4-[(e)-3-(4-fluorophenyl)-3-[(e)-1-(4-fluorophenyl)-3-(2,3,4-trifluorophenyl)prop-2-enyl]sulfonylprop-1-enyl]benzene Chemical compound C1=CC(F)=CC=C1C(S(=O)(=O)C(\C=C\C=1C(=C(F)C(F)=CC=1)F)C=1C=CC(F)=CC=1)\C=C\C1=CC=C(F)C(F)=C1F YFQFBQIGRJQFFS-BGPOSVGRSA-N 0.000 claims 1
- OHLGBRUJXZLENF-WGDLNXRISA-N 1-[(e)-3-(4-chlorophenyl)-3-[(e)-1-(4-chlorophenyl)-3-(2,3,4,5,6-pentafluorophenyl)prop-2-enyl]sulfonylprop-1-enyl]-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=C(F)C(F)=C(F)C=1F)F)C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 OHLGBRUJXZLENF-WGDLNXRISA-N 0.000 claims 1
- ASWIUWIUYBQFRE-BGPOSVGRSA-N 1-[(e)-3-(4-chlorophenyl)-3-[(e)-1-(4-chlorophenyl)-3-(2,3,4-trifluorophenyl)prop-2-enyl]sulfonylprop-1-enyl]-2,3,4-trifluorobenzene Chemical compound FC1=C(F)C(F)=CC=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=C(F)C(F)=CC=1)F)C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 ASWIUWIUYBQFRE-BGPOSVGRSA-N 0.000 claims 1
- IXKPKFXAOWLGBA-YTEMWHBBSA-N 2-[(e)-3-(4-bromophenyl)-3-[(e)-1-(4-bromophenyl)-3-(2,4,6-trimethoxyphenyl)prop-2-enyl]sulfonylprop-1-enyl]-1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=CC(OC)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=CC(OC)=CC=1OC)OC)C=1C=CC(Br)=CC=1)C1=CC=C(Br)C=C1 IXKPKFXAOWLGBA-YTEMWHBBSA-N 0.000 claims 1
- PNYMULXLZQBRJS-WXUKJITCSA-N 2-[(e)-3-(4-chlorophenyl)-3-[(e)-1-(4-chlorophenyl)-3-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-enyl]sulfonylprop-1-enyl]-3,5-dimethoxyphenol Chemical compound COC1=CC(OC)=CC(O)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=CC(OC)=CC=1O)OC)C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 PNYMULXLZQBRJS-WXUKJITCSA-N 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 9
- 230000001028 anti-proliverative effect Effects 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 67
- 230000008018 melting Effects 0.000 description 38
- 238000002844 melting Methods 0.000 description 38
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 21
- 125000004429 atom Chemical group 0.000 description 19
- 239000000203 mixture Substances 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 17
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 15
- 229910052708 sodium Inorganic materials 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 230000003647 oxidation Effects 0.000 description 14
- 238000007254 oxidation reaction Methods 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 14
- MXXQOAGTJXSSCB-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methylsulfonyl]acetic acid Chemical compound COC1=CC=C(CS(=O)(=O)CC(O)=O)C=C1 MXXQOAGTJXSSCB-UHFFFAOYSA-N 0.000 description 13
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 13
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- HPWAJMXOEYIERK-UHFFFAOYSA-N 2-benzylsulfonylacetic acid Chemical class OC(=O)CS(=O)(=O)CC1=CC=CC=C1 HPWAJMXOEYIERK-UHFFFAOYSA-N 0.000 description 11
- 125000005504 styryl group Chemical group 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 10
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 10
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 10
- 102000043136 MAP kinase family Human genes 0.000 description 10
- 108091054455 MAP kinase family Proteins 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 238000007911 parenteral administration Methods 0.000 description 9
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 8
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 8
- MRTIWTGAGMZREP-VAWYXSNFSA-N [(e)-2-phenylethenyl]sulfonylmethylbenzene Chemical class C=1C=CC=CC=1/C=C/S(=O)(=O)CC1=CC=CC=C1 MRTIWTGAGMZREP-VAWYXSNFSA-N 0.000 description 8
- MRTIWTGAGMZREP-QXMHVHEDSA-N [(z)-2-phenylethenyl]sulfonylmethylbenzene Chemical class C=1C=CC=CC=1\C=C/S(=O)(=O)CC1=CC=CC=C1 MRTIWTGAGMZREP-QXMHVHEDSA-N 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- YYXBXAYHHCTPEF-UHFFFAOYSA-N 2-[(4-chlorophenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=CC=C(Cl)C=C1 YYXBXAYHHCTPEF-UHFFFAOYSA-N 0.000 description 7
- JZLMLFCJWFMZMC-UHFFFAOYSA-N 3-phenylpropanethioic s-acid Chemical compound SC(=O)CCC1=CC=CC=C1 JZLMLFCJWFMZMC-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QJXCFMJTJYCLFG-UHFFFAOYSA-N 2,3,4,5,6-pentafluorobenzaldehyde Chemical compound FC1=C(F)C(F)=C(C=O)C(F)=C1F QJXCFMJTJYCLFG-UHFFFAOYSA-N 0.000 description 6
- CRBZVDLXAIFERF-UHFFFAOYSA-N 2,4,6-trimethoxybenzaldehyde Chemical compound COC1=CC(OC)=C(C=O)C(OC)=C1 CRBZVDLXAIFERF-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WZDKIPVHBCBPCR-QXMHVHEDSA-N [(z)-2-benzylsulfanylethenyl]benzene Chemical compound C=1C=CC=CC=1CS\C=C/C1=CC=CC=C1 WZDKIPVHBCBPCR-QXMHVHEDSA-N 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- PBEXVWXHXPEARD-UHFFFAOYSA-N 1-ethynyl-2,3,4,5,6-pentafluorobenzene Chemical group FC1=C(F)C(F)=C(C#C)C(F)=C1F PBEXVWXHXPEARD-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 150000003934 aromatic aldehydes Chemical class 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229940073608 benzyl chloride Drugs 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- CJGJGYUEZKDRNF-UHFFFAOYSA-N 2-[(2,3,4,5,6-pentafluorophenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=C(F)C(F)=C(F)C(F)=C1F CJGJGYUEZKDRNF-UHFFFAOYSA-N 0.000 description 4
- CMWSJQKBSMKODK-UHFFFAOYSA-N 2-[(4,5-dimethoxy-2-nitrophenyl)methylsulfonyl]acetic acid Chemical compound COC1=CC(CS(=O)(=O)CC(O)=O)=C([N+]([O-])=O)C=C1OC CMWSJQKBSMKODK-UHFFFAOYSA-N 0.000 description 4
- VMYFZBLZKJJKLR-UHFFFAOYSA-N 2-[(4-bromophenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=CC=C(Br)C=C1 VMYFZBLZKJJKLR-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 230000004668 G2/M phase Effects 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 4
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 4
- 230000002939 deleterious effect Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 229940093915 gynecological organic acid Drugs 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 235000005985 organic acids Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- JREFDYBVCHRUMO-UHFFFAOYSA-N (2,3,4-trimethoxyphenyl)methanethiol Chemical compound COC1=CC=C(CS)C(OC)=C1OC JREFDYBVCHRUMO-UHFFFAOYSA-N 0.000 description 3
- UCTUXUGXIFRVGX-UHFFFAOYSA-N 2,3,4-trimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1OC UCTUXUGXIFRVGX-UHFFFAOYSA-N 0.000 description 3
- VNXKPPDFXDGURH-UHFFFAOYSA-N 2-[(2,3,4-trimethoxyphenyl)methylsulfonyl]acetic acid Chemical compound COC1=CC=C(CS(=O)(=O)CC(O)=O)C(OC)=C1OC VNXKPPDFXDGURH-UHFFFAOYSA-N 0.000 description 3
- STQLDAZMDJUSKV-UHFFFAOYSA-N 2-[(4-fluorophenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=CC=C(F)C=C1 STQLDAZMDJUSKV-UHFFFAOYSA-N 0.000 description 3
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 3
- WIXUJZCQKBKJKV-UHFFFAOYSA-N 4-fluoro-2,3-dimethoxybenzaldehyde Chemical compound COC1=C(F)C=CC(C=O)=C1OC WIXUJZCQKBKJKV-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- PHTXVQQRWJXYPP-UHFFFAOYSA-N ethyltrifluoromethylaminoindane Chemical compound C1=C(C(F)(F)F)C=C2CC(NCC)CC2=C1 PHTXVQQRWJXYPP-UHFFFAOYSA-N 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- OUMRUWRPTBYLRS-UHFFFAOYSA-N phenylmethanethiol;sodium Chemical compound [Na].SCC1=CC=CC=C1 OUMRUWRPTBYLRS-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- SNCHEDBJOUWPMJ-UHFFFAOYSA-M sodium;phenylmethanethiolate Chemical compound [Na+].[S-]CC1=CC=CC=C1 SNCHEDBJOUWPMJ-UHFFFAOYSA-M 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- WBBBQLNBASXWLG-UHFFFAOYSA-N (2,4,6-trimethoxyphenyl)methanethiol Chemical compound COC1=CC(OC)=C(CS)C(OC)=C1 WBBBQLNBASXWLG-UHFFFAOYSA-N 0.000 description 2
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 2
- UQEDGFZRPSAHLC-UHFFFAOYSA-N 2,3,4-trifluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(F)=C1F UQEDGFZRPSAHLC-UHFFFAOYSA-N 0.000 description 2
- JIVGSHFYXPRRSZ-UHFFFAOYSA-N 2,3-dimethoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1OC JIVGSHFYXPRRSZ-UHFFFAOYSA-N 0.000 description 2
- HIKRJHFHGKZKRI-UHFFFAOYSA-N 2,4,6-trimethylbenzaldehyde Chemical compound CC1=CC(C)=C(C=O)C(C)=C1 HIKRJHFHGKZKRI-UHFFFAOYSA-N 0.000 description 2
- XCFZREFJMPXNSD-UHFFFAOYSA-N 2-[(3,4,5-trimethoxyphenyl)methylsulfonyl]acetic acid Chemical compound COC1=CC(CS(=O)(=O)CC(O)=O)=CC(OC)=C1OC XCFZREFJMPXNSD-UHFFFAOYSA-N 0.000 description 2
- AFQNSIQCYHWDSF-UHFFFAOYSA-N 2-[(4-iodophenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=CC=C(I)C=C1 AFQNSIQCYHWDSF-UHFFFAOYSA-N 0.000 description 2
- FQRQWPNYJOFDLO-UHFFFAOYSA-N 2-hydroxy-4,6-dimethoxybenzaldehyde Chemical compound COC1=CC(O)=C(C=O)C(OC)=C1 FQRQWPNYJOFDLO-UHFFFAOYSA-N 0.000 description 2
- YCTNWTBGSOCMRO-UHFFFAOYSA-N 3,5-dinitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC(C=O)=CC([N+]([O-])=O)=C1 YCTNWTBGSOCMRO-UHFFFAOYSA-N 0.000 description 2
- FLJXIBHYDIMYRS-UHFFFAOYSA-N 3,5-dinitrosalicylaldehyde Chemical compound OC1=C(C=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O FLJXIBHYDIMYRS-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 2
- 125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 2
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000003064 anti-oxidating effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- AWHNUHMUCGRKRA-UHFFFAOYSA-N benzylsulfonylmethylbenzene Chemical compound C=1C=CC=CC=1CS(=O)(=O)CC1=CC=CC=C1 AWHNUHMUCGRKRA-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 2
- 229960002023 chloroprocaine Drugs 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 2
- 230000001672 cytoproliferative effect Effects 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 229940043237 diethanolamine Drugs 0.000 description 2
- 229940012017 ethylenediamine Drugs 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 230000003463 hyperproliferative effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960003194 meglumine Drugs 0.000 description 2
- QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 2
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 230000000865 phosphorylative effect Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 229960004919 procaine Drugs 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229910052701 rubidium Inorganic materials 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- GNBVPFITFYNRCN-UHFFFAOYSA-M sodium thioglycolate Chemical compound [Na+].[O-]C(=O)CS GNBVPFITFYNRCN-UHFFFAOYSA-M 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- PDKCUIQKBZNCCO-UHFFFAOYSA-N (2,4,5-trimethoxyphenyl)methanethiol Chemical compound COC1=CC(OC)=C(OC)C=C1CS PDKCUIQKBZNCCO-UHFFFAOYSA-N 0.000 description 1
- RAYRIBHSFSJNJQ-UHFFFAOYSA-N (2-ethynylphenyl)phosphonic acid Chemical group OP(O)(=O)C1=CC=CC=C1C#C RAYRIBHSFSJNJQ-UHFFFAOYSA-N 0.000 description 1
- OAZXFACSERDEDY-UHFFFAOYSA-N (3,4,5-trimethoxyphenyl)methanethiol Chemical compound COC1=CC(CS)=CC(OC)=C1OC OAZXFACSERDEDY-UHFFFAOYSA-N 0.000 description 1
- GKQXPTHQTXCXEV-UHFFFAOYSA-N (4-chlorophenyl)methanethiol Chemical compound SCC1=CC=C(Cl)C=C1 GKQXPTHQTXCXEV-UHFFFAOYSA-N 0.000 description 1
- UGPZOWXCYINLLF-UHFFFAOYSA-N (4-ethynyl-2-methoxyphenyl) acetate Chemical group COC1=CC(C#C)=CC=C1OC(C)=O UGPZOWXCYINLLF-UHFFFAOYSA-N 0.000 description 1
- FWYJPCBQOURGOR-UHFFFAOYSA-N (4-ethynylphenyl)phosphonic acid Chemical group OP(O)(=O)C1=CC=C(C#C)C=C1 FWYJPCBQOURGOR-UHFFFAOYSA-N 0.000 description 1
- PTDVPWWJRCOIIO-UHFFFAOYSA-N (4-methoxyphenyl)methanethiol Chemical compound COC1=CC=C(CS)C=C1 PTDVPWWJRCOIIO-UHFFFAOYSA-N 0.000 description 1
- AGFYZLVFPSGUIX-UHFFFAOYSA-N (4-methylphenyl)methanethiol Chemical compound CC1=CC=C(CS)C=C1 AGFYZLVFPSGUIX-UHFFFAOYSA-N 0.000 description 1
- ACFHLWCEZHYYKX-UHFFFAOYSA-N (4-nitrophenyl)methanethiol Chemical compound [O-][N+](=O)C1=CC=C(CS)C=C1 ACFHLWCEZHYYKX-UHFFFAOYSA-N 0.000 description 1
- MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical compound C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 description 1
- OSNUAOGZQIJIJZ-FOIMCPNXSA-N 1,2,3,4,5-pentafluoro-6-[(Z)-3-[(Z)-3-(2,3,4,5,6-pentafluorophenyl)-1-(2,3,4-trimethoxyphenyl)prop-2-enyl]sulfanyl-3-(2,3,4-trimethoxyphenyl)prop-1-enyl]benzene Chemical compound FC1=C(C(=C(C(=C1\C=C/C(C1=C(C(=C(C=C1)OC)OC)OC)SC(C1=C(C(=C(C=C1)OC)OC)OC)\C=C/C1=C(C(=C(C(=C1F)F)F)F)F)F)F)F)F OSNUAOGZQIJIJZ-FOIMCPNXSA-N 0.000 description 1
- RAAQBYYORYWILP-XOHWUJONSA-N 1,2,3,4,5-pentafluoro-6-[(Z)-3-[(Z)-3-(2,3,4,5,6-pentafluorophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-enyl]sulfanyl-3-(2,4,6-trimethoxyphenyl)prop-1-enyl]benzene Chemical compound FC1=C(C(=C(C(=C1\C=C/C(C1=C(C=C(C=C1OC)OC)OC)SC(C1=C(C=C(C=C1OC)OC)OC)\C=C/C1=C(C(=C(C(=C1F)F)F)F)F)F)F)F)F RAAQBYYORYWILP-XOHWUJONSA-N 0.000 description 1
- BNEIPBFBGWXIAU-XOHWUJONSA-N 1,2,3,4,5-pentafluoro-6-[(Z)-3-[(Z)-3-(2,3,4,5,6-pentafluorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-enyl]sulfanyl-3-(3,4,5-trimethoxyphenyl)prop-1-enyl]benzene Chemical compound FC1=C(C(=C(C(=C1\C=C/C(C1=CC(=C(C(=C1)OC)OC)OC)SC(C1=CC(=C(C(=C1)OC)OC)OC)\C=C/C1=C(C(=C(C(=C1F)F)F)F)F)F)F)F)F BNEIPBFBGWXIAU-XOHWUJONSA-N 0.000 description 1
- SKYZIRRSHQQLDF-XOHWUJONSA-N 1,2,3,4,5-pentafluoro-6-[(Z)-3-[(Z)-3-(2,3,4,5,6-pentafluorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-enyl]sulfonyl-3-(3,4,5-trimethoxyphenyl)prop-1-enyl]benzene Chemical compound FC1=C(C(=C(C(=C1\C=C/C(C1=CC(=C(C(=C1)OC)OC)OC)S(=O)(=O)C(C1=CC(=C(C(=C1)OC)OC)OC)\C=C/C1=C(C(=C(C(=C1F)F)F)F)F)F)F)F)F SKYZIRRSHQQLDF-XOHWUJONSA-N 0.000 description 1
- YYMQAYHDWNTLSF-LQGKIZFRSA-N 1,2,3-trimethoxy-5-[(e)-3-(4-methoxyphenyl)-3-[(e)-1-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-enyl]sulfonylprop-1-enyl]benzene Chemical compound C1=CC(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C=C(OC)C(OC)=C(OC)C=1)C=1C=CC(OC)=CC=1)\C=C\C1=CC(OC)=C(OC)C(OC)=C1 YYMQAYHDWNTLSF-LQGKIZFRSA-N 0.000 description 1
- KYCUTWIDMOHAHN-PHEQNACWSA-N 1,2,4,5-tetrafluoro-3-[(e)-3-(4-methoxyphenyl)-3-[(e)-1-(4-methoxyphenyl)-3-(2,3,5,6-tetrafluorophenyl)prop-2-enyl]sulfonylprop-1-enyl]benzene Chemical compound C1=CC(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C(=C(F)C=C(F)C=1F)F)C=1C=CC(OC)=CC=1)\C=C\C1=C(F)C(F)=CC(F)=C1F KYCUTWIDMOHAHN-PHEQNACWSA-N 0.000 description 1
- JQFCLOCJSVBNSU-XSYHWHKQSA-N 1,3,5-trifluoro-2-[(z)-3-(4-methylphenyl)-3-[(z)-1-(4-methylphenyl)-3-(2,4,6-trifluorophenyl)prop-2-enyl]sulfanylprop-1-enyl]benzene Chemical compound C1=CC(C)=CC=C1C(\C=C/C=1C(=CC(F)=CC=1F)F)SC(C=1C=CC(C)=CC=1)\C=C/C1=C(F)C=C(F)C=C1F JQFCLOCJSVBNSU-XSYHWHKQSA-N 0.000 description 1
- JDNFRLGQKKVVQT-HWAYABPNSA-N 1,3,5-trifluoro-2-[(z)-3-(4-nitrophenyl)-3-[(z)-1-(4-nitrophenyl)-3-(2,4,6-trifluorophenyl)prop-2-enyl]sulfanylprop-1-enyl]benzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(\C=C/C=1C(=CC(F)=CC=1F)F)SC(C=1C=CC(=CC=1)[N+]([O-])=O)\C=C/C1=C(F)C=C(F)C=C1F JDNFRLGQKKVVQT-HWAYABPNSA-N 0.000 description 1
- UMWIYEIWGHFIHY-BLVCXSLXSA-N 1-[(e)-3-(2,6-dimethoxyphenyl)-1-[(e)-3-(2,6-dimethoxyphenyl)-1-(2,3,4-trimethoxyphenyl)prop-2-enyl]sulfonylprop-2-enyl]-2,3,4-trimethoxybenzene Chemical compound COC1=C(OC)C(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C(=CC=CC=1OC)OC)C=1C(=C(OC)C(OC)=CC=1)OC)\C=C\C1=C(OC)C=CC=C1OC UMWIYEIWGHFIHY-BLVCXSLXSA-N 0.000 description 1
- GDTUGCWXSHJEJM-XHQRYOPUSA-N 1-[(e)-3-(4-fluorophenyl)-1-[(e)-3-(4-fluorophenyl)-1-(2,3,4-trimethoxyphenyl)prop-2-enyl]sulfonylprop-2-enyl]-2,3,4-trimethoxybenzene Chemical compound COC1=C(OC)C(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C=CC(F)=CC=1)C=1C(=C(OC)C(OC)=CC=1)OC)\C=C\C1=CC=C(F)C=C1 GDTUGCWXSHJEJM-XHQRYOPUSA-N 0.000 description 1
- KPYJCIWZUILFQQ-DFEHQXHXSA-N 1-[(e)-3-[(e)-3-(2,4-dimethoxy-3-methylphenyl)-1-(4-methoxyphenyl)prop-2-enyl]sulfonyl-3-(4-methoxyphenyl)prop-1-enyl]-2,4-dimethoxy-3-methylbenzene Chemical compound C1=CC(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C(=C(C)C(OC)=CC=1)OC)C=1C=CC(OC)=CC=1)\C=C\C1=CC=C(OC)C(C)=C1OC KPYJCIWZUILFQQ-DFEHQXHXSA-N 0.000 description 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- YIRYOMXPMOLQSO-UHFFFAOYSA-N 2,3,5,6-tetrafluorobenzaldehyde Chemical compound FC1=CC(F)=C(F)C(C=O)=C1F YIRYOMXPMOLQSO-UHFFFAOYSA-N 0.000 description 1
- IAJBQAYHSQIQRE-UHFFFAOYSA-N 2,4,5-trimethoxybenzaldehyde Chemical compound COC1=CC(OC)=C(C=O)C=C1OC IAJBQAYHSQIQRE-UHFFFAOYSA-N 0.000 description 1
- UOKAZUWUHOBBMD-UHFFFAOYSA-N 2,4-dimethoxy-3-methylbenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1C UOKAZUWUHOBBMD-UHFFFAOYSA-N 0.000 description 1
- LWRSYTXEQUUTKW-UHFFFAOYSA-N 2,4-dimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1 LWRSYTXEQUUTKW-UHFFFAOYSA-N 0.000 description 1
- WXSGQHKHUYTJNB-UHFFFAOYSA-N 2,6-dimethoxybenzaldehyde Chemical compound COC1=CC=CC(OC)=C1C=O WXSGQHKHUYTJNB-UHFFFAOYSA-N 0.000 description 1
- VYQDJILQMWAPKX-UHFFFAOYSA-N 2-[(1,3,4,5,6-pentafluorocyclohexa-2,4-dien-1-yl)methylsulfonyl]acetic acid Chemical compound FC1(CS(=O)(=O)CC(=O)O)C(C(=C(C(=C1)F)F)F)F VYQDJILQMWAPKX-UHFFFAOYSA-N 0.000 description 1
- IGHOQZIXSOUKCP-UHFFFAOYSA-N 2-[(2,4-dichlorophenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=CC=C(Cl)C=C1Cl IGHOQZIXSOUKCP-UHFFFAOYSA-N 0.000 description 1
- OAGVGSFXLRIMDW-UHFFFAOYSA-N 2-[(2-methoxy-5-nitrophenyl)methylsulfonyl]acetic acid Chemical compound COC1=CC=C([N+]([O-])=O)C=C1CS(=O)(=O)CC(O)=O OAGVGSFXLRIMDW-UHFFFAOYSA-N 0.000 description 1
- OYUBAPFRCZGIEH-UHFFFAOYSA-N 2-[(2-methoxyphenyl)methylsulfonyl]acetic acid Chemical compound COC1=CC=CC=C1CS(=O)(=O)CC(O)=O OYUBAPFRCZGIEH-UHFFFAOYSA-N 0.000 description 1
- GKJGKCRDFKGLBB-UHFFFAOYSA-N 2-[(3,4-dichlorophenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=CC=C(Cl)C(Cl)=C1 GKJGKCRDFKGLBB-UHFFFAOYSA-N 0.000 description 1
- IGLREYWKSDXWCK-UHFFFAOYSA-N 2-[(3,5-dimethoxyphenyl)methylsulfonyl]acetic acid Chemical compound COC1=CC(CS(=O)(=O)CC(O)=O)=CC(OC)=C1 IGLREYWKSDXWCK-UHFFFAOYSA-N 0.000 description 1
- DGZLPEXTGJUEHL-UHFFFAOYSA-N 2-[(4-cyanophenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=CC=C(C#N)C=C1 DGZLPEXTGJUEHL-UHFFFAOYSA-N 0.000 description 1
- DUAHZALXWPOQET-UHFFFAOYSA-N 2-[(4-hydroxyphenyl)methylsulfonyl]acetic acid Chemical compound OC(=O)CS(=O)(=O)CC1=CC=C(O)C=C1 DUAHZALXWPOQET-UHFFFAOYSA-N 0.000 description 1
- ICQSOKWFTKHUNG-UHFFFAOYSA-N 2-[3-[[4-(trifluoromethyl)phenyl]methyl]thiophen-2-yl]acetic acid Chemical compound S1C=CC(CC=2C=CC(=CC=2)C(F)(F)F)=C1CC(=O)O ICQSOKWFTKHUNG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- NOPWUXRFETZTQG-UHFFFAOYSA-N 2-ethynyl-1,3,5-trifluorobenzene Chemical group FC1=CC(F)=C(C#C)C(F)=C1 NOPWUXRFETZTQG-UHFFFAOYSA-N 0.000 description 1
- KTLQDZRFPKXZSB-UHFFFAOYSA-N 2-ethynylphenol Chemical group OC1=CC=CC=C1C#C KTLQDZRFPKXZSB-UHFFFAOYSA-N 0.000 description 1
- MRTIWTGAGMZREP-UHFFFAOYSA-N 2-phenylethenylsulfonylmethylbenzene Chemical class C=1C=CC=CC=1C=CS(=O)(=O)CC1=CC=CC=C1 MRTIWTGAGMZREP-UHFFFAOYSA-N 0.000 description 1
- AAPXXKYXVIBBEC-UHFFFAOYSA-N 3-(1,3,4,5,6-pentafluorocyclohexa-2,4-dien-1-yl)propanethioic s-acid Chemical compound FC1C(F)=C(F)C(F)=CC1(F)CCC(S)=O AAPXXKYXVIBBEC-UHFFFAOYSA-N 0.000 description 1
- JSLNNPDSKUVEDI-UHFFFAOYSA-N 3-(2,3,4-trimethoxyphenyl)propanethioic s-acid Chemical compound COC1=CC=C(CCC(O)=S)C(OC)=C1OC JSLNNPDSKUVEDI-UHFFFAOYSA-N 0.000 description 1
- JGDPJQXJDUVLNW-UHFFFAOYSA-N 3-(2,4,6-trimethoxyphenyl)propanethioic s-acid Chemical compound COC1=CC(OC)=C(CCC(O)=S)C(OC)=C1 JGDPJQXJDUVLNW-UHFFFAOYSA-N 0.000 description 1
- DAINKWFIXCZUPS-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)propanethioic s-acid Chemical compound OC(=S)CCC1=CC=C(Cl)C=C1Cl DAINKWFIXCZUPS-UHFFFAOYSA-N 0.000 description 1
- SKPAXFBIMHGXNZ-UHFFFAOYSA-N 3-(2,4-dimethoxyphenyl)propanethioic s-acid Chemical compound COC1=CC=C(CCC(O)=S)C(OC)=C1 SKPAXFBIMHGXNZ-UHFFFAOYSA-N 0.000 description 1
- VRULWRCOKFDAPS-UHFFFAOYSA-N 3-(2-methoxy-5-nitrophenyl)propanethioic s-acid Chemical compound COC1=CC=C([N+]([O-])=O)C=C1CCC(O)=S VRULWRCOKFDAPS-UHFFFAOYSA-N 0.000 description 1
- WJSPWHVIKYVWAP-UHFFFAOYSA-N 3-(2-methoxyphenyl)propanethioic s-acid Chemical compound COC1=CC=CC=C1CCC(O)=S WJSPWHVIKYVWAP-UHFFFAOYSA-N 0.000 description 1
- JHPYIJVOAIFJMK-UHFFFAOYSA-N 3-(4,5-dimethoxy-2-nitrophenyl)propanethioic s-acid Chemical compound COC1=CC(CCC(O)=S)=C([N+]([O-])=O)C=C1OC JHPYIJVOAIFJMK-UHFFFAOYSA-N 0.000 description 1
- DZJGBLPJFDBGQG-UHFFFAOYSA-N 3-(4-cyanophenyl)propanethioic s-acid Chemical compound OC(=S)CCC1=CC=C(C#N)C=C1 DZJGBLPJFDBGQG-UHFFFAOYSA-N 0.000 description 1
- CCKZXPIUQIWQGO-UHFFFAOYSA-N 3-(4-hydroxyphenyl)propanethioic s-acid Chemical compound OC1=CC=C(CCC(S)=O)C=C1 CCKZXPIUQIWQGO-UHFFFAOYSA-N 0.000 description 1
- KWSLBFZQQBSEGJ-UHFFFAOYSA-N 3-(4-iodophenyl)propanethioic s-acid Chemical compound OC(=S)CCC1=CC=C(I)C=C1 KWSLBFZQQBSEGJ-UHFFFAOYSA-N 0.000 description 1
- MVPNBXPAUYYZAF-UHFFFAOYSA-N 3-iodo-4,5-dimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(I)=C1OC MVPNBXPAUYYZAF-UHFFFAOYSA-N 0.000 description 1
- YWSPWKXREVSQCA-UHFFFAOYSA-N 4,5-dimethoxy-2-nitrobenzaldehyde Chemical compound COC1=CC(C=O)=C([N+]([O-])=O)C=C1OC YWSPWKXREVSQCA-UHFFFAOYSA-N 0.000 description 1
- VZIHYNYGMYSLRN-IAGONARPSA-N 4-[(e)-3-[(e)-3-(4-hydroxy-3-methoxy-5-nitrophenyl)-1-(4-methoxyphenyl)prop-2-enyl]sulfonyl-3-(4-methoxyphenyl)prop-1-enyl]-2-methoxy-6-nitrophenol Chemical compound C1=CC(OC)=CC=C1C(S(=O)(=O)C(\C=C\C=1C=C(C(O)=C(OC)C=1)[N+]([O-])=O)C=1C=CC(OC)=CC=1)\C=C\C1=CC(OC)=C(O)C([N+]([O-])=O)=C1 VZIHYNYGMYSLRN-IAGONARPSA-N 0.000 description 1
- JKZCQBRWPKRUNV-FOIMCPNXSA-N 4-[(z)-3-[(z)-3-(3,4-dihydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-enyl]sulfanyl-3-(2,4,6-trimethoxyphenyl)prop-1-enyl]benzene-1,2-diol Chemical compound COC1=CC(OC)=CC(OC)=C1C(\C=C/C=1C=C(O)C(O)=CC=1)SC(C=1C(=CC(OC)=CC=1OC)OC)\C=C/C1=CC=C(O)C(O)=C1 JKZCQBRWPKRUNV-FOIMCPNXSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- WKSQMKBWJAFJQR-UHFFFAOYSA-N 4-ethynylbenzene-1,2-diol Chemical group OC1=CC=C(C#C)C=C1O WKSQMKBWJAFJQR-UHFFFAOYSA-N 0.000 description 1
- YMWYSWXWDNMUIX-UHFFFAOYSA-N 4-hydroxy-2,3-dimethoxybenzaldehyde Chemical compound COC1=C(O)C=CC(C=O)=C1OC YMWYSWXWDNMUIX-UHFFFAOYSA-N 0.000 description 1
- GEPNDNHWSRLLIX-XPWSMXQVSA-N 5-[(e)-3-(2,6-dimethoxyphenyl)-1-[(e)-3-(2,6-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-enyl]sulfonylprop-2-enyl]-1,2,3-trimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1\C=C\C(S(=O)(=O)C(\C=C\C=1C(=CC=CC=1OC)OC)C=1C=C(OC)C(OC)=C(OC)C=1)C1=CC(OC)=C(OC)C(OC)=C1 GEPNDNHWSRLLIX-XPWSMXQVSA-N 0.000 description 1
- BYXGJWKPRWVUQF-PHEQNACWSA-N 5-[(e)-3-(4,5-dimethoxy-2-nitrophenyl)-3-[(e)-1-(4,5-dimethoxy-2-nitrophenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-enyl]sulfonylprop-1-enyl]-1,2,3-trimethoxybenzene Chemical compound C1=C(OC)C(OC)=CC(C(\C=C\C=2C=C(OC)C(OC)=C(OC)C=2)S(=O)(=O)C(\C=C\C=2C=C(OC)C(OC)=C(OC)C=2)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)=C1[N+]([O-])=O BYXGJWKPRWVUQF-PHEQNACWSA-N 0.000 description 1
- ZEHYRTJBFMZHCY-UHFFFAOYSA-N 5-nitrovanillin Chemical compound COC1=CC(C=O)=CC([N+]([O-])=O)=C1O ZEHYRTJBFMZHCY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 101100397594 Ancylostoma caninum JNK-1 gene Proteins 0.000 description 1
- CMSOZIPKZAKXNO-UHFFFAOYSA-N COC1=C(C(OC)(OC)S)C=CC=C1 Chemical compound COC1=C(C(OC)(OC)S)C=CC=C1 CMSOZIPKZAKXNO-UHFFFAOYSA-N 0.000 description 1
- GFCVZDIYVBXUOS-UHFFFAOYSA-N COC=1C=C(C=C/C(C2=C(C=C(C(=C2)OC)OC)OC)S(=O)(=O)C(C2=C(C=C(C(=C2)OC)OC)OC)C=C/C2=CC(=C(C=C2)OC(C)=O)OC)C=CC1OC(C)=O Chemical compound COC=1C=C(C=C/C(C2=C(C=C(C(=C2)OC)OC)OC)S(=O)(=O)C(C2=C(C=C(C(=C2)OC)OC)OC)C=C/C2=CC(=C(C=C2)OC(C)=O)OC)C=CC1OC(C)=O GFCVZDIYVBXUOS-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108030004793 Dual-specificity kinases Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- FDCQCBWQAQBYNR-UHFFFAOYSA-N FC1=C(C=C/C(C2=CC=C(C=C2)C)S(=O)(=O)C(C2=CC=C(C=C2)C)C=C/C2=C(C=C(C=C2F)F)F)C(=CC(=C1)F)F Chemical compound FC1=C(C=C/C(C2=CC=C(C=C2)C)S(=O)(=O)C(C2=CC=C(C=C2)C)C=C/C2=C(C=C(C=C2F)F)F)C(=CC(=C1)F)F FDCQCBWQAQBYNR-UHFFFAOYSA-N 0.000 description 1
- XCLCBCFHVSBCEY-XSYHWHKQSA-N FC1=C(Cl)C(F)=C(F)C(C(F)(SC(F)(\C=C/C=2C=CC=CC=2)C=2C(=C(F)C(Cl)=C(F)C=2F)F)\C=C/C=2C=CC=CC=2)=C1F Chemical compound FC1=C(Cl)C(F)=C(F)C(C(F)(SC(F)(\C=C/C=2C=CC=CC=2)C=2C(=C(F)C(Cl)=C(F)C=2F)F)\C=C/C=2C=CC=CC=2)=C1F XCLCBCFHVSBCEY-XSYHWHKQSA-N 0.000 description 1
- SAGXDSLBTUHLQP-XSYHWHKQSA-N FC1=C(Cl)C(F)=C(F)C(C(F)(\C=C/C=2C=CC=CC=2)S(=O)(=O)C(F)(\C=C/C=2C=CC=CC=2)C=2C(=C(F)C(Cl)=C(F)C=2F)F)=C1F Chemical compound FC1=C(Cl)C(F)=C(F)C(C(F)(\C=C/C=2C=CC=CC=2)S(=O)(=O)C(F)(\C=C/C=2C=CC=CC=2)C=2C(=C(F)C(Cl)=C(F)C=2F)F)=C1F SAGXDSLBTUHLQP-XSYHWHKQSA-N 0.000 description 1
- BWJNJYVHFPKGNT-VMNXYWKNSA-N FC1=C(F)C(OC)=C(F)C(F)=C1C(F)(\C=C/C=1C=CC=CC=1)SC(F)(C=1C(=C(F)C(OC)=C(F)C=1F)F)\C=C/C1=CC=CC=C1 Chemical compound FC1=C(F)C(OC)=C(F)C(F)=C1C(F)(\C=C/C=1C=CC=CC=1)SC(F)(C=1C(=C(F)C(OC)=C(F)C=1F)F)\C=C/C1=CC=CC=C1 BWJNJYVHFPKGNT-VMNXYWKNSA-N 0.000 description 1
- 102100028701 General vesicular transport factor p115 Human genes 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 101000767151 Homo sapiens General vesicular transport factor p115 Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100434906 Mus musculus Angptl8 gene Proteins 0.000 description 1
- JBICOERTUDTBKX-UHFFFAOYSA-N OC1=C(C=C/C(C2=C(C=C(C=C2OC)OC)OC)S(=O)(=O)C(C2=C(C=C(C=C2OC)OC)OC)C=C/C2=C(C=CC=C2)O)C=CC=C1 Chemical compound OC1=C(C=C/C(C2=C(C=C(C=C2OC)OC)OC)S(=O)(=O)C(C2=C(C=C(C=C2OC)OC)OC)C=C/C2=C(C=CC=C2)O)C=CC=C1 JBICOERTUDTBKX-UHFFFAOYSA-N 0.000 description 1
- OSDZNPVHPQJMET-UHFFFAOYSA-N OC1=C(C=C/C(C2=C(C=C(C=C2OC)OC)OC)SC(C2=C(C=C(C=C2OC)OC)OC)C=C/C2=C(C=CC=C2)O)C=CC=C1 Chemical compound OC1=C(C=C/C(C2=C(C=C(C=C2OC)OC)OC)SC(C2=C(C=C(C=C2OC)OC)OC)C=C/C2=C(C=CC=C2)O)C=CC=C1 OSDZNPVHPQJMET-UHFFFAOYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 241000237988 Patellidae Species 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108010016131 Proto-Oncogene Proteins c-jun Proteins 0.000 description 1
- 102000000427 Proto-Oncogene Proteins c-jun Human genes 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- LKEKWDJCJSPXNI-IRIUXVKKSA-N Thr-Glu-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 LKEKWDJCJSPXNI-IRIUXVKKSA-N 0.000 description 1
- YGZWVPBHYABGLT-KJEVXHAQSA-N Thr-Pro-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 YGZWVPBHYABGLT-KJEVXHAQSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- LRZOZXZWSAWUQA-JTFWXBGUSA-N [4-[(z)-3-[(z)-3-(4-acetyloxy-3-methoxyphenyl)-1-(2,4,5-trimethoxyphenyl)prop-2-enyl]sulfanyl-3-(2,4,5-trimethoxyphenyl)prop-1-enyl]-2-methoxyphenyl] acetate Chemical compound C1=C(OC(C)=O)C(OC)=CC(\C=C/C(SC(\C=C/C=2C=C(OC)C(OC(C)=O)=CC=2)C=2C(=CC(OC)=C(OC)C=2)OC)C=2C(=CC(OC)=C(OC)C=2)OC)=C1 LRZOZXZWSAWUQA-JTFWXBGUSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- DNAVOCNYHNNEQI-UHFFFAOYSA-N asaronaldehyde Natural products COC1=CC(OC)=C(C=CC=O)C=C1OC DNAVOCNYHNNEQI-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 150000005524 benzylchlorides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 125000002474 dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000000394 phosphonato group Chemical group [O-]P([O-])(*)=O 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000020071 rectified spirit Nutrition 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000004767 rumen Anatomy 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 150000003440 styrenes Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000010304 tumor cell viability Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 231100000747 viability assay Toxicity 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/02—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to acyclic carbon atoms
- C07C317/10—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/18—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/12—Esters of phosphoric acids with hydroxyaryl compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Reproductive Health (AREA)
- Molecular Biology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US19784900P | 2000-04-14 | 2000-04-14 | |
| US23470700P | 2000-09-22 | 2000-09-22 | |
| US27164001P | 2001-02-27 | 2001-02-27 | |
| PCT/US2001/012134 WO2001078712A1 (en) | 2000-04-14 | 2001-04-13 | Substituted styryl benzylsulfones for treating proliferative disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ522551A true NZ522551A (en) | 2004-03-26 |
Family
ID=27393791
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ522551A NZ522551A (en) | 2000-04-14 | 2001-04-13 | Substituted styryl benzylsulfones for treating cancer and other proliferative diseases |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6486210B2 (enExample) |
| EP (2) | EP1305015B1 (enExample) |
| JP (1) | JP4677162B2 (enExample) |
| KR (1) | KR100768415B1 (enExample) |
| AU (2) | AU2001251615C1 (enExample) |
| CA (1) | CA2406212C (enExample) |
| DK (1) | DK1305015T3 (enExample) |
| ES (1) | ES2427088T3 (enExample) |
| IL (2) | IL152190A0 (enExample) |
| NZ (1) | NZ522551A (enExample) |
| PT (1) | PT1305015E (enExample) |
| SI (1) | SI1305015T1 (enExample) |
| WO (1) | WO2001078712A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6762207B1 (en) * | 1999-04-02 | 2004-07-13 | Temple University - Of The Commonwealth System Of Higher Education | (E)-styryl sulfone anticancer agents |
| CA2424884C (en) | 2000-10-05 | 2009-12-15 | E. Premkumar Reddy | Substituted (e)-styryl benzylsulfones for treating proliferative disorders |
| US6833480B2 (en) * | 2001-02-27 | 2004-12-21 | Temple University - Of The Commonwealth System Of Higher Education | (Z)-styrylbenzylsulfones and pharmaceutical uses thereof |
| ATE406881T1 (de) | 2001-02-28 | 2008-09-15 | Univ Temple | Verwendung von alpha, beta ungesättigten arylsulfonen zum schutz von zellen und geweben vor toxizität ionischer strahlung |
| MXPA04008356A (es) * | 2002-02-28 | 2005-09-12 | Univ Temple | (e)-2,6-dialcoxiestiril bencilsulfonas sustituidas con un grupo amino y en la posicion 4 para tratar trastornos poliferativos. |
| ATE517626T1 (de) * | 2002-02-28 | 2011-08-15 | Univ Temple | Aminosubstituierte sulphonanilide und ihre derivate zur behandlung von proliferativen erkrankungen |
| JP4182844B2 (ja) * | 2003-09-03 | 2008-11-19 | 株式会社島津製作所 | 質量分析装置 |
| HUE032523T2 (en) * | 2003-11-14 | 2017-09-28 | Temple Univ - Of The Commonwealth System Of Higher Education | Alpha, beta-unsaturated sulfoxides for the treatment of proliferative disorders |
| ES2609084T3 (es) * | 2004-03-16 | 2017-04-18 | Temple University - Of The Commonwealth System Of Higher Education | Derivados de fenoxi y feniltio sustituidos para tratar trastornos proliferativos |
| CA2577309C (en) | 2004-06-24 | 2013-10-22 | Temple University - Of The Commonwealth System Of Higher Education | Alpha, beta-unsaturated sulfones, sulfoxides, sulfonimides, sulfinimides, acylsulfonamides and acylsulfinamides and therapeutic uses thereof |
| AU2006204103B2 (en) * | 2005-01-05 | 2011-11-24 | Temple University Of The Commonwealth System Of Higher Education | Treatment of drug-resistant proliferative disorders |
| PT1896401E (pt) * | 2005-02-25 | 2013-07-17 | Univ Temple | Síntese de sulfuretos, sulfonas, sulfóxidos e sulfonamidas não saturados |
| WO2006104668A2 (en) * | 2005-03-11 | 2006-10-05 | Temple University - Of The Commonwealth System Of Higher Education | Composition and methods for the treatment of proliferative diseases |
| JP5278968B2 (ja) * | 2006-08-30 | 2013-09-04 | テンプル・ユニバーシティ−オブ・ザ・コモンウェルス・システム・オブ・ハイアー・エデュケイション | 骨髄異形性症候群及び急性骨髄性白血病の治療のための組成物及び方法 |
| US8273787B2 (en) * | 2006-09-15 | 2012-09-25 | Onconova Therapeutics, Inc | Activated cytotoxic compounds for attachment to targeting molecules for the treatment of mammalian disease conditions |
| US8735620B2 (en) * | 2008-12-17 | 2014-05-27 | Epr Pharmaceuticals Pvt. Ltd | Processes for preparing (E)-styrylbenzylsulfone compounds and uses thereof for treating proliferative disorders |
| US10207989B2 (en) | 2012-09-20 | 2019-02-19 | Temple University—Of the Commonwealth System of Higher Education | Substituted alkyl diaryl derivatives, methods of preparation and uses |
| WO2014089483A1 (en) | 2012-12-07 | 2014-06-12 | Onconova Therapeutics, Inc. | Methods and compositions for treatment of cancer |
| US10383831B2 (en) | 2015-08-03 | 2019-08-20 | Temple University—Of the Commonwealth System of Higher Education | 2,4,6-trialkoxystryl aryl sulfones, sulfonamides and carboxamides, and methods of preparation and use |
| WO2024186641A1 (en) * | 2023-03-03 | 2024-09-12 | Onconova Therapeutics, Inc. | Methods and compositions for treating cancer |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2532612A (en) | 1945-08-29 | 1950-12-05 | Union Oil Co | Preparation of unsaturated thio-ethers |
| US3185743A (en) | 1960-08-24 | 1965-05-25 | Union Carbide Corp | Production of olefinic compounds from allyl sulfones |
| US3418101A (en) | 1965-12-15 | 1968-12-24 | Pennsalt Chemicals Corp | Process for plant desiccation |
| US3514386A (en) | 1967-12-11 | 1970-05-26 | Exxon Research Engineering Co | Stereoselective addition of thiols to acetylenic compounds |
| US3917714A (en) | 1972-09-06 | 1975-11-04 | American Cyanamid Co | Bis(alkylsulfonyl)vinylbenzenes |
| US4161407A (en) | 1977-10-06 | 1979-07-17 | Eastman Kodak Company | Crosslinkable polymers having vinylsulfonyl groups or styrylsulfonyl groups and their use as hardeners for gelatin |
| US4386221A (en) | 1981-10-28 | 1983-05-31 | Eastman Kodak Company | Process for the preparation of aryl alkyl sulfones and aryl vinyl sulfones |
| US4937388A (en) | 1985-08-09 | 1990-06-26 | Imperial Chemical Industries Plc | Insecticidal ethers |
| YU213587A (en) * | 1986-11-28 | 1989-06-30 | Orion Yhtymae Oy | Process for obtaining new pharmacologic active cateholic derivatives |
| FR2621038B1 (fr) * | 1987-09-28 | 1989-12-29 | Rhone Poulenc Sante | Derives d'alcadienes, leurs preparations, les medicaments les contenant et produits intermediaires |
| GB8902409D0 (en) * | 1989-02-03 | 1989-03-22 | Ici Plc | Aliphatic compounds |
| US5659087A (en) | 1995-06-07 | 1997-08-19 | Eli Lilly And Company | Diarylvinyl sulfoxides |
| JP3660395B2 (ja) * | 1995-06-22 | 2005-06-15 | 大鵬薬品工業株式会社 | フェニルスルホン誘導体及びその製造方法 |
| CZ290756B6 (cs) * | 1995-10-19 | 2002-10-16 | Ciba Specialty Chemicals Holding Inc. | Substituované fenoly působící jako antioxidanty, kompozice, které je obsahují, a jejich pouľití |
| ATE284386T1 (de) | 1997-10-03 | 2004-12-15 | Univ Temple | Styrolsulfone als antikrebsmittel |
| US6201154B1 (en) * | 1999-03-31 | 2001-03-13 | Temple University-Of The Commonwealth Of Higher Education | Z-styryl sulfone anticancer agents |
| JP2002541101A (ja) * | 1999-04-02 | 2002-12-03 | テンプル・ユニバーシティ−オブ・ザ・コモンウェルス・システム・オブ・ハイアー・エデュケイション | スチリルスルホン抗癌剤 |
| CA2366750C (en) * | 1999-04-02 | 2010-06-01 | Temple University - Of The Commonwealth System Of Higher Education | (e)-styryl sulfone anticancer agents |
| AU780844B2 (en) * | 1999-10-12 | 2005-04-21 | Temple University-Of The Commonwealth System Of Higher Education | Method for protecting normal cells from cytotoxicity of chemotherapeutic agents |
-
2001
- 2001-04-12 US US09/833,287 patent/US6486210B2/en not_active Expired - Lifetime
- 2001-04-13 EP EP01925014.1A patent/EP1305015B1/en not_active Expired - Lifetime
- 2001-04-13 WO PCT/US2001/012134 patent/WO2001078712A1/en not_active Ceased
- 2001-04-13 DK DK01925014.1T patent/DK1305015T3/da active
- 2001-04-13 CA CA2406212A patent/CA2406212C/en not_active Expired - Lifetime
- 2001-04-13 KR KR1020027013708A patent/KR100768415B1/ko not_active Expired - Lifetime
- 2001-04-13 AU AU2001251615A patent/AU2001251615C1/en not_active Expired
- 2001-04-13 SI SI200131022T patent/SI1305015T1/sl unknown
- 2001-04-13 PT PT1925014T patent/PT1305015E/pt unknown
- 2001-04-13 ES ES01925014T patent/ES2427088T3/es not_active Expired - Lifetime
- 2001-04-13 JP JP2001576013A patent/JP4677162B2/ja not_active Expired - Lifetime
- 2001-04-13 EP EP10178360A patent/EP2359819A1/en not_active Withdrawn
- 2001-04-13 IL IL15219001A patent/IL152190A0/xx unknown
- 2001-04-13 NZ NZ522551A patent/NZ522551A/en not_active IP Right Cessation
- 2001-04-13 AU AU5161501A patent/AU5161501A/xx active Pending
-
2002
- 2002-07-29 US US10/207,429 patent/US6642410B2/en not_active Expired - Lifetime
- 2002-10-08 IL IL152190A patent/IL152190A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| DK1305015T3 (da) | 2013-08-26 |
| IL152190A0 (en) | 2003-05-29 |
| US20030036536A1 (en) | 2003-02-20 |
| AU2001251615C1 (en) | 2006-12-07 |
| KR20030029044A (ko) | 2003-04-11 |
| AU2001251615B2 (en) | 2005-08-11 |
| WO2001078712A1 (en) | 2001-10-25 |
| US6642410B2 (en) | 2003-11-04 |
| EP2359819A1 (en) | 2011-08-24 |
| CA2406212A1 (en) | 2001-10-25 |
| EP1305015A1 (en) | 2003-05-02 |
| SI1305015T1 (sl) | 2013-08-30 |
| IL152190A (en) | 2010-11-30 |
| AU5161501A (en) | 2001-10-30 |
| EP1305015A4 (en) | 2003-05-21 |
| PT1305015E (pt) | 2013-09-06 |
| EP1305015B1 (en) | 2013-06-12 |
| CA2406212C (en) | 2011-02-01 |
| JP2003530433A (ja) | 2003-10-14 |
| US6486210B2 (en) | 2002-11-26 |
| JP4677162B2 (ja) | 2011-04-27 |
| ES2427088T3 (es) | 2013-10-28 |
| KR100768415B1 (ko) | 2007-10-18 |
| US20020115643A1 (en) | 2002-08-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6642410B2 (en) | Substituted benzylthioacetic acids and esters | |
| AU2001251615A1 (en) | Substituted styryl benzylsulfones for treating proliferative disorders | |
| US6787667B2 (en) | (E)-styryl sulfone anticancer agents | |
| JP4468593B2 (ja) | Ｚ−スチリルスルホン抗癌剤 | |
| US6548553B2 (en) | Styryl sulfone anticancer agents | |
| US20020028818A1 (en) | Alpha, beta-unsaturated sulfones for treating proliferative disorders | |
| EP1173160B1 (en) | (e)-styryl sulfone anticancer agents | |
| US7053123B2 (en) | Substituted (e)-styryl benzylsulfones for treating proliferative disorders | |
| WO2002067913A8 (en) | (z)-styrylbenzylsulfones and pharmaceutical uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| S38A | Application for proceedings under section 38 (amendment of specification with leave of commissioner) |
Free format text: BY WAY OF CORRECTION |
|
| S38C | Proceedings under section 38 (amendment of specification with leave of commissioner): specification amended | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) |
Free format text: PATENT RENEWED FOR 7 YEARS UNTIL 13 APR 2021 BY COMPUTER PACKAGES INC Effective date: 20140429 |
|
| EXPY | Patent expired |