DE69828079T2 - Styrolsulfone als antikrebsmittel - Google Patents
Styrolsulfone als antikrebsmittel Download PDFInfo
- Publication number
- DE69828079T2 DE69828079T2 DE69828079T DE69828079T DE69828079T2 DE 69828079 T2 DE69828079 T2 DE 69828079T2 DE 69828079 T DE69828079 T DE 69828079T DE 69828079 T DE69828079 T DE 69828079T DE 69828079 T2 DE69828079 T2 DE 69828079T2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- cells
- hydrogen
- mol
- fluorine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 title 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 81
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 30
- 239000001257 hydrogen Substances 0.000 claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
- 239000011737 fluorine Chemical group 0.000 claims abstract description 23
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 23
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 22
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000000460 chlorine Chemical group 0.000 claims abstract description 20
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 20
- -1 2-nitrophenyl Chemical group 0.000 claims abstract description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052794 bromium Chemical group 0.000 claims abstract description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 12
- 230000006907 apoptotic process Effects 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims abstract description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 3
- 201000011510 cancer Diseases 0.000 claims abstract description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 26
- 206010006187 Breast cancer Diseases 0.000 claims description 19
- 208000026310 Breast neoplasm Diseases 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 14
- 210000000481 breast Anatomy 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 206010060862 Prostate cancer Diseases 0.000 claims description 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
- GMKXPTFOBQFAOD-MDZDMXLPSA-N 1-chloro-4-[[(e)-2-(4-fluorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(F)=CC=C1\C=C\S(=O)(=O)CC1=CC=C(Cl)C=C1 GMKXPTFOBQFAOD-MDZDMXLPSA-N 0.000 claims description 6
- WXVZZCHUAIGQKJ-MDZDMXLPSA-N 1-chloro-4-[[(e)-2-(4-chlorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(Cl)=CC=C1CS(=O)(=O)\C=C\C1=CC=C(Cl)C=C1 WXVZZCHUAIGQKJ-MDZDMXLPSA-N 0.000 claims description 5
- JJSHRTVHJFKOFB-MDZDMXLPSA-N 1-[[(e)-2-(4-bromophenyl)ethenyl]sulfonylmethyl]-4-chlorobenzene Chemical compound C1=CC(Cl)=CC=C1CS(=O)(=O)\C=C\C1=CC=C(Br)C=C1 JJSHRTVHJFKOFB-MDZDMXLPSA-N 0.000 claims description 3
- CHQQDELDVCBHKN-MDZDMXLPSA-N 1-bromo-4-[[(e)-2-(4-fluorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(F)=CC=C1\C=C\S(=O)(=O)CC1=CC=C(Br)C=C1 CHQQDELDVCBHKN-MDZDMXLPSA-N 0.000 claims description 3
- NXLVMMFSYHOBNA-BQYQJAHWSA-N 2,4-difluoro-1-[(e)-2-[(4-fluorophenyl)methylsulfonyl]ethenyl]benzene Chemical compound C1=CC(F)=CC=C1CS(=O)(=O)\C=C\C1=CC=C(F)C=C1F NXLVMMFSYHOBNA-BQYQJAHWSA-N 0.000 claims description 3
- 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 3
- URBLDUHDENNTET-MDZDMXLPSA-N 1-[[(e)-2-(4-bromophenyl)ethenyl]sulfonylmethyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1CS(=O)(=O)\C=C\C1=CC=C(Br)C=C1 URBLDUHDENNTET-MDZDMXLPSA-N 0.000 claims description 2
- HVSMMGMOGXMVNZ-MDZDMXLPSA-N 1-bromo-4-[(e)-2-(4-chlorophenyl)sulfonylethenyl]benzene Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)\C=C\C1=CC=C(Br)C=C1 HVSMMGMOGXMVNZ-MDZDMXLPSA-N 0.000 claims description 2
- ZDYHTOFOTBKCFQ-MDZDMXLPSA-N 1-bromo-4-[[(e)-2-(4-chlorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(Cl)=CC=C1\C=C\S(=O)(=O)CC1=CC=C(Br)C=C1 ZDYHTOFOTBKCFQ-MDZDMXLPSA-N 0.000 claims description 2
- BHZSVOGMDVLRRR-MDZDMXLPSA-N 1-chloro-4-[(e)-2-(4-chlorophenyl)sulfonylethenyl]benzene Chemical compound C1=CC(Cl)=CC=C1\C=C\S(=O)(=O)C1=CC=C(Cl)C=C1 BHZSVOGMDVLRRR-MDZDMXLPSA-N 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- RPDRBEJDYHVLME-ZHACJKMWSA-N 1-[(e)-2-(benzenesulfonyl)ethenyl]-4-bromobenzene Chemical compound C1=CC(Br)=CC=C1\C=C\S(=O)(=O)C1=CC=CC=C1 RPDRBEJDYHVLME-ZHACJKMWSA-N 0.000 claims 1
- BPCWSTIDUJXABN-MDZDMXLPSA-N 1-bromo-4-[[(e)-2-(4-bromophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(Br)=CC=C1CS(=O)(=O)\C=C\C1=CC=C(Br)C=C1 BPCWSTIDUJXABN-MDZDMXLPSA-N 0.000 claims 1
- QFXKVNVCBJMHBH-MDZDMXLPSA-N 1-fluoro-4-[[(e)-2-(4-fluorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(F)=CC=C1CS(=O)(=O)\C=C\C1=CC=C(F)C=C1 QFXKVNVCBJMHBH-MDZDMXLPSA-N 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract description 102
- XJNHONCWGODPIZ-PHEQNACWSA-N [(e)-2-[(e)-2-phenylethenyl]sulfonylethenyl]benzene Chemical class C=1C=CC=CC=1/C=C/S(=O)(=O)\C=C\C1=CC=CC=C1 XJNHONCWGODPIZ-PHEQNACWSA-N 0.000 abstract description 5
- 230000035755 proliferation Effects 0.000 abstract description 2
- 125000001153 fluoro group Chemical group F* 0.000 abstract 1
- 238000000034 method Methods 0.000 description 51
- 239000000243 solution Substances 0.000 description 43
- 230000000694 effects Effects 0.000 description 31
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 27
- 108090000623 proteins and genes Proteins 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 21
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 102000043136 MAP kinase family Human genes 0.000 description 18
- 108091054455 MAP kinase family Proteins 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000006166 lysate Substances 0.000 description 14
- 208000023958 prostate neoplasm Diseases 0.000 description 14
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
- 239000003098 androgen Substances 0.000 description 12
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 12
- 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 11
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 11
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 11
- 230000026731 phosphorylation Effects 0.000 description 11
- 238000006366 phosphorylation reaction Methods 0.000 description 11
- 230000035899 viability Effects 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 230000022131 cell cycle Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 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 description 9
- 230000007717 exclusion Effects 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 102000047918 Myelin Basic Human genes 0.000 description 8
- 101710107068 Myelin basic protein Proteins 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- HPWAJMXOEYIERK-UHFFFAOYSA-N 2-benzylsulfonylacetic acid Chemical class OC(=O)CS(=O)(=O)CC1=CC=CC=C1 HPWAJMXOEYIERK-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 150000003934 aromatic aldehydes Chemical class 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 102000015694 estrogen receptors Human genes 0.000 description 7
- 108010038795 estrogen receptors Proteins 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- WCOXFTGMNJJABC-SREVYHEPSA-N 2-[(z)-2-phenylethenyl]sulfonylacetic acid Chemical compound OC(=O)CS(=O)(=O)\C=C/C1=CC=CC=C1 WCOXFTGMNJJABC-SREVYHEPSA-N 0.000 description 6
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 6
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 6
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis 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
- 238000001262 western blot Methods 0.000 description 6
- XJNHONCWGODPIZ-AOGCGKDYSA-N 2-[(e)-2-phenylethenyl]sulfonylethenylbenzene Chemical class C=1C=CC=CC=1/C=C/S(=O)(=O)C=CC1=CC=CC=C1 XJNHONCWGODPIZ-AOGCGKDYSA-N 0.000 description 5
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 5
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
- 108090000412 Protein-Tyrosine Kinases Proteins 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
- 239000000872 buffer Substances 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 5
- 229960004316 cisplatin Drugs 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 229940079826 hydrogen sulfite Drugs 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- IAONCYGNBVHNCT-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfonylacetic acid Chemical compound OC(=O)CS(=O)(=O)C1=CC=C(Cl)C=C1 IAONCYGNBVHNCT-UHFFFAOYSA-N 0.000 description 4
- YTEFAALYDTWTLB-UHFFFAOYSA-N 2-(benzenesulfonyl)acetic acid Chemical compound OC(=O)CS(=O)(=O)C1=CC=CC=C1 YTEFAALYDTWTLB-UHFFFAOYSA-N 0.000 description 4
- 101100397594 Ancylostoma caninum JNK-1 gene Proteins 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000012139 lysis buffer Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 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 3
- 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 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
- XJNHONCWGODPIZ-CSXFVWEESA-N 2-[(Z)-2-phenylethenyl]sulfonylethenylbenzene Chemical class C(=C/C1=CC=CC=C1)/S(=O)(=O)C=CC1=CC=CC=C1 XJNHONCWGODPIZ-CSXFVWEESA-N 0.000 description 3
- 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 3
- XMBPHCAGUFSFOJ-UHFFFAOYSA-N 3-oxo-4-sulfonylbutanoic acid Chemical compound S(=O)(=O)=CC(CC(=O)O)=O XMBPHCAGUFSFOJ-UHFFFAOYSA-N 0.000 description 3
- SEUYMUDVXBSSGT-UHFFFAOYSA-N 4-phenylbut-3-enethioic s-acid Chemical compound SC(=O)CC=CC1=CC=CC=C1 SEUYMUDVXBSSGT-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000010337 G2 phase Effects 0.000 description 3
- 239000007995 HEPES buffer 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
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000000211 autoradiogram Methods 0.000 description 3
- DHCLVCXQIBBOPH-UHFFFAOYSA-N beta-glycerol phosphate Natural products OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 3
- GHRQXJHBXKYCLZ-UHFFFAOYSA-L beta-glycerolphosphate Chemical compound [Na+].[Na+].CC(CO)OOP([O-])([O-])=O GHRQXJHBXKYCLZ-UHFFFAOYSA-L 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 229940106681 chloroacetic acid Drugs 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
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000000021 kinase assay Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000017095 negative regulation of cell growth Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 210000005267 prostate cell Anatomy 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- SYTHOKWALOYRAP-UHFFFAOYSA-N 2-[2-chloro-3-(2-chloro-3-phenacylphenyl)sulfonylphenyl]-1-phenylethanone Chemical compound C1=CC=C(S(=O)(=O)C=2C(=C(CC(=O)C=3C=CC=CC=3)C=CC=2)Cl)C(Cl)=C1CC(=O)C1=CC=CC=C1 SYTHOKWALOYRAP-UHFFFAOYSA-N 0.000 description 2
- JXHLDZVRNMLMEB-UHFFFAOYSA-N 2-[5-fluoro-2-(4-fluoro-2-phenacylphenyl)sulfonylphenyl]-1-phenylethanone Chemical compound C=1C(F)=CC=C(S(=O)(=O)C=2C(=CC(F)=CC=2)CC(=O)C=2C=CC=CC=2)C=1CC(=O)C1=CC=CC=C1 JXHLDZVRNMLMEB-UHFFFAOYSA-N 0.000 description 2
- 108010039627 Aprotinin Proteins 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 2
- 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 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
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 108010016131 Proto-Oncogene Proteins c-jun Proteins 0.000 description 2
- 102000000427 Proto-Oncogene Proteins c-jun Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 102100023132 Transcription factor Jun Human genes 0.000 description 2
- 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 2
- 239000002253 acid Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 230000033228 biological regulation Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000006353 environmental stress Effects 0.000 description 2
- 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 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
- 108010052968 leupeptin Proteins 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
- 239000012528 membrane Substances 0.000 description 2
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 2
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 230000000865 phosphorylative effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 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
- 210000002307 prostate Anatomy 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- GNBVPFITFYNRCN-UHFFFAOYSA-M sodium thioglycolate Chemical compound [Na+].[O-]C(=O)CS GNBVPFITFYNRCN-UHFFFAOYSA-M 0.000 description 2
- 229940046307 sodium thioglycolate Drugs 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000004565 tumor cell growth Effects 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
- 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 1
- IKYQZECJDCGOGL-KAVGSWPWSA-N 1-[(E)-2-(4-bromophenyl)ethenyl]-2-[2-[(E)-2-(4-bromophenyl)ethenyl]phenyl]sulfonylbenzene Chemical compound BrC1=CC=C(/C=C/C2=C(C=CC=C2)S(=O)(=O)C2=C(C=CC=C2)\C=C\C2=CC=C(C=C2)Br)C=C1 IKYQZECJDCGOGL-KAVGSWPWSA-N 0.000 description 1
- SMASTKAYSZUPPH-KAVGSWPWSA-N 1-[(E)-2-(4-chlorophenyl)ethenyl]-2-[2-[(E)-2-(4-chlorophenyl)ethenyl]phenyl]sulfonylbenzene Chemical compound C1=CC=C(C(=C1)/C=C/C2=CC=C(C=C2)Cl)S(=O)(=O)C3=CC=CC=C3/C=C/C4=CC=C(C=C4)Cl SMASTKAYSZUPPH-KAVGSWPWSA-N 0.000 description 1
- GMZMXCZTVDOYNX-ZHACJKMWSA-N 1-[(e)-2-(4-chlorophenyl)sulfonylethenyl]-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1\C=C\S(=O)(=O)C1=CC=C(Cl)C=C1 GMZMXCZTVDOYNX-ZHACJKMWSA-N 0.000 description 1
- LUFVQVKHWIYXIB-ZHACJKMWSA-N 1-[(e)-2-(4-chlorophenyl)sulfonylethenyl]-4-methylbenzene Chemical compound C1=CC(C)=CC=C1\C=C\S(=O)(=O)C1=CC=C(Cl)C=C1 LUFVQVKHWIYXIB-ZHACJKMWSA-N 0.000 description 1
- FRASOWAJKUTNBZ-FLFKKZLDSA-N 1-chloro-2-[(E)-3-[(E)-3-(2-chlorophenyl)-1-phenylprop-2-enyl]sulfonyl-3-phenylprop-1-enyl]benzene Chemical compound C1=CC=C(C=C1)C(S(=O)(=O)C(C2=CC=CC=C2)/C=C/C3=CC=CC=C3Cl)/C=C/C4=CC=CC=C4Cl FRASOWAJKUTNBZ-FLFKKZLDSA-N 0.000 description 1
- BPHHGVVRRWDEFE-YHARCJFQSA-N 1-chloro-4-[(E)-3-[(E)-3-(4-chlorophenyl)-1-phenylprop-2-enyl]sulfonyl-3-phenylprop-1-enyl]benzene Chemical compound C1=CC=C(C=C1)C(S(=O)(=O)C(C2=CC=CC=C2)/C=C/C3=CC=C(C=C3)Cl)/C=C/C4=CC=C(C=C4)Cl BPHHGVVRRWDEFE-YHARCJFQSA-N 0.000 description 1
- ZTJSBCQWMGJOIN-WGDLNXRISA-N 2,4-dichloro-1-[(E)-2-[2-[2-[(E)-2-(2,4-dichlorophenyl)ethenyl]phenyl]sulfonylphenyl]ethenyl]benzene Chemical compound ClC1=C(/C=C/C2=C(C=CC=C2)S(=O)(=O)C2=C(C=CC=C2)\C=C\C2=C(C=C(C=C2)Cl)Cl)C=CC(=C1)Cl ZTJSBCQWMGJOIN-WGDLNXRISA-N 0.000 description 1
- YSFBEAASFUWWHU-UHFFFAOYSA-N 2,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C(Cl)=C1 YSFBEAASFUWWHU-UHFFFAOYSA-N 0.000 description 1
- WCGPCBACLBHDCI-UHFFFAOYSA-N 2,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(F)=C1 WCGPCBACLBHDCI-UHFFFAOYSA-N 0.000 description 1
- RAFWRUNTUFYFAC-UHFFFAOYSA-N 2-(2-chlorophenyl)sulfonyl-3-(4-fluorophenyl)-1-phenylprop-2-en-1-one Chemical compound C1=CC(F)=CC=C1C=C(S(=O)(=O)C=1C(=CC=CC=1)Cl)C(=O)C1=CC=CC=C1 RAFWRUNTUFYFAC-UHFFFAOYSA-N 0.000 description 1
- WCOXFTGMNJJABC-UHFFFAOYSA-N 2-(2-phenylethenylsulfonyl)acetic acid Chemical compound OC(=O)CS(=O)(=O)C=CC1=CC=CC=C1 WCOXFTGMNJJABC-UHFFFAOYSA-N 0.000 description 1
- DREVPGKOIZVPQV-UHFFFAOYSA-N 2-(benzenesulfonyl)-1-phenylethanone Chemical compound C=1C=CC=CC=1C(=O)CS(=O)(=O)C1=CC=CC=C1 DREVPGKOIZVPQV-UHFFFAOYSA-N 0.000 description 1
- RIUCTGMEDZCYKZ-UHFFFAOYSA-N 2-[2-nitro-3-(2-nitro-3-phenacylphenyl)sulfonylphenyl]-1-phenylethanone Chemical compound C1=CC=C(S(=O)(=O)C=2C(=C(CC(=O)C=3C=CC=CC=3)C=CC=2)[N+]([O-])=O)C([N+](=O)[O-])=C1CC(=O)C1=CC=CC=C1 RIUCTGMEDZCYKZ-UHFFFAOYSA-N 0.000 description 1
- DSNUPUMBSSCFHS-UHFFFAOYSA-N 2-[5-bromo-2-(4-bromo-2-phenacylphenyl)sulfonylphenyl]-1-phenylethanone Chemical compound C=1C(Br)=CC=C(S(=O)(=O)C=2C(=CC(Br)=CC=2)CC(=O)C=2C=CC=CC=2)C=1CC(=O)C1=CC=CC=C1 DSNUPUMBSSCFHS-UHFFFAOYSA-N 0.000 description 1
- WXBWJTDIRGOOAN-UHFFFAOYSA-N 2-[5-chloro-2-(4-chloro-2-phenacylphenyl)sulfonylphenyl]-1-phenylethanone Chemical compound C=1C(Cl)=CC=C(S(=O)(=O)C=2C(=CC(Cl)=CC=2)CC(=O)C=2C=CC=CC=2)C=1CC(=O)C1=CC=CC=C1 WXBWJTDIRGOOAN-UHFFFAOYSA-N 0.000 description 1
- AMJUCPMWRHEFEO-UHFFFAOYSA-N 2-[5-methoxy-2-(4-methoxy-2-phenacylphenyl)sulfonylphenyl]-1-phenylethanone Chemical compound C=1C(OC)=CC=C(S(=O)(=O)C=2C(=CC(OC)=CC=2)CC(=O)C=2C=CC=CC=2)C=1CC(=O)C1=CC=CC=C1 AMJUCPMWRHEFEO-UHFFFAOYSA-N 0.000 description 1
- YPAMEUJNJVCLNP-UHFFFAOYSA-N 2-[5-nitro-2-(4-nitro-2-phenacylphenyl)sulfonylphenyl]-1-phenylethanone Chemical compound C=1C([N+](=O)[O-])=CC=C(S(=O)(=O)C=2C(=CC(=CC=2)[N+]([O-])=O)CC(=O)C=2C=CC=CC=2)C=1CC(=O)C1=CC=CC=C1 YPAMEUJNJVCLNP-UHFFFAOYSA-N 0.000 description 1
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 1
- VYNUATGQEAAPAQ-UHFFFAOYSA-N 2-sulfonylacetic acid Chemical compound OC(=O)C=S(=O)=O VYNUATGQEAAPAQ-UHFFFAOYSA-N 0.000 description 1
- KWVKOYBKUXUKDS-UHFFFAOYSA-N 3-(4-bromophenyl)-2-(2-chlorophenyl)sulfonyl-1-phenylprop-2-en-1-one Chemical compound ClC1=CC=CC=C1S(=O)(=O)C(C(=O)C=1C=CC=CC=1)=CC1=CC=C(Br)C=C1 KWVKOYBKUXUKDS-UHFFFAOYSA-N 0.000 description 1
- QAWBXYVZQVGZAP-UHFFFAOYSA-N 3-(4-bromophenyl)-2-(2-nitrophenyl)sulfonyl-1-phenylprop-2-en-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1S(=O)(=O)C(C(=O)C=1C=CC=CC=1)=CC1=CC=C(Br)C=C1 QAWBXYVZQVGZAP-UHFFFAOYSA-N 0.000 description 1
- NKEZKRHTIDOVSX-UHFFFAOYSA-N 3-(4-bromophenyl)-2-(4-chlorophenyl)sulfonyl-1-phenylprop-2-en-1-one Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC=CC=1)=CC1=CC=C(Br)C=C1 NKEZKRHTIDOVSX-UHFFFAOYSA-N 0.000 description 1
- HKSMWZCEBDDOSD-UHFFFAOYSA-N 3-(4-fluorophenyl)-2-(4-fluorophenyl)sulfonyl-1-phenylprop-2-en-1-one Chemical compound C1=CC(F)=CC=C1C=C(S(=O)(=O)C=1C=CC(F)=CC=1)C(=O)C1=CC=CC=C1 HKSMWZCEBDDOSD-UHFFFAOYSA-N 0.000 description 1
- JZLMLFCJWFMZMC-UHFFFAOYSA-N 3-phenylpropanethioic s-acid Chemical class SC(=O)CCC1=CC=CC=C1 JZLMLFCJWFMZMC-UHFFFAOYSA-N 0.000 description 1
- UOWDFWHJQHACJQ-MJBGKLQRSA-N C(C)(=O)O.C(=C/C1=CC=CC=C1)/S(=O)(=O)\C=C/C1=CC=CC=C1 Chemical compound C(C)(=O)O.C(=C/C1=CC=CC=C1)/S(=O)(=O)\C=C/C1=CC=CC=C1 UOWDFWHJQHACJQ-MJBGKLQRSA-N 0.000 description 1
- ATQYXMMYXOTCDA-JQBMIRIKSA-N C1=CC(Br)=CC=C1\C=C(\S(=O)(=O)\C(\C=C/C=1C=CC=CC=1)=C\C=1C=CC(Br)=CC=1)/C=C\C1=CC=CC=C1 Chemical compound C1=CC(Br)=CC=C1\C=C(\S(=O)(=O)\C(\C=C/C=1C=CC=CC=1)=C\C=1C=CC(Br)=CC=1)/C=C\C1=CC=CC=C1 ATQYXMMYXOTCDA-JQBMIRIKSA-N 0.000 description 1
- RXIAYSLAWGTXBE-JQBMIRIKSA-N C1=CC(Cl)=CC=C1\C=C(\S(=O)(=O)\C(\C=C/C=1C=CC=CC=1)=C\C=1C=CC(Cl)=CC=1)/C=C\C1=CC=CC=C1 Chemical compound C1=CC(Cl)=CC=C1\C=C(\S(=O)(=O)\C(\C=C/C=1C=CC=CC=1)=C\C=1C=CC(Cl)=CC=1)/C=C\C1=CC=CC=C1 RXIAYSLAWGTXBE-JQBMIRIKSA-N 0.000 description 1
- YHCMQPPHPAYPQM-JQBMIRIKSA-N C1=CC(F)=CC=C1\C=C(\S(=O)(=O)\C(\C=C/C=1C=CC=CC=1)=C\C=1C=CC(F)=CC=1)/C=C\C1=CC=CC=C1 Chemical compound C1=CC(F)=CC=C1\C=C(\S(=O)(=O)\C(\C=C/C=1C=CC=CC=1)=C\C=1C=CC(F)=CC=1)/C=C\C1=CC=CC=C1 YHCMQPPHPAYPQM-JQBMIRIKSA-N 0.000 description 1
- XJNHONCWGODPIZ-XSYHWHKQSA-N C=1C=CC=CC=1\C=C/S(=O)(=O)\C=C/C1=CC=CC=C1 Chemical class C=1C=CC=CC=1\C=C/S(=O)(=O)\C=C/C1=CC=CC=C1 XJNHONCWGODPIZ-XSYHWHKQSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 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
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- DNMCCXFLTURVLK-VAWYXSNFSA-N [(e)-2-(benzenesulfonyl)ethenyl]benzene Chemical compound C=1C=CC=CC=1S(=O)(=O)\C=C\C1=CC=CC=C1 DNMCCXFLTURVLK-VAWYXSNFSA-N 0.000 description 1
- WZDKIPVHBCBPCR-QXMHVHEDSA-N [(z)-2-benzylsulfanylethenyl]benzene Chemical class C=1C=CC=CC=1CS\C=C/C1=CC=CC=C1 WZDKIPVHBCBPCR-QXMHVHEDSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 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
- 239000012298 atmosphere Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 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
- 238000009835 boiling Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000003085 diluting agent Substances 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
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 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
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- QXLPXWSKPNOQLE-UHFFFAOYSA-N methylpentynol Chemical compound CCC(C)(O)C#C QXLPXWSKPNOQLE-UHFFFAOYSA-N 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 229920002113 octoxynol Polymers 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
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical class BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- OAHKWDDSKCRNFE-UHFFFAOYSA-N phenylmethanesulfonyl chloride Chemical compound ClS(=O)(=O)CC1=CC=CC=C1 OAHKWDDSKCRNFE-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 108091005981 phosphorylated proteins Proteins 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000131 polyvinylidene Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating 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
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 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
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/12—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/14—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (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)
- Graft Or Block Polymers (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6093397P | 1997-10-03 | 1997-10-03 | |
| US60933P | 1997-10-03 | ||
| PCT/US1998/020580 WO1999018068A1 (en) | 1997-10-03 | 1998-10-01 | Styryl sulfone anticancer agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69828079D1 DE69828079D1 (de) | 2005-01-13 |
| DE69828079T2 true DE69828079T2 (de) | 2005-12-22 |
Family
ID=22032642
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69828079T Expired - Lifetime DE69828079T2 (de) | 1997-10-03 | 1998-10-01 | Styrolsulfone als antikrebsmittel |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US6359013B1 (enExample) |
| EP (1) | EP1027330B1 (enExample) |
| JP (1) | JP4294217B2 (enExample) |
| KR (1) | KR100579355B1 (enExample) |
| CN (1) | CN1163480C (enExample) |
| AT (1) | ATE284386T1 (enExample) |
| AU (1) | AU741042B2 (enExample) |
| BR (1) | BR9814059B1 (enExample) |
| CA (1) | CA2305790C (enExample) |
| CZ (1) | CZ299718B6 (enExample) |
| DE (1) | DE69828079T2 (enExample) |
| IL (1) | IL135438A (enExample) |
| NZ (1) | NZ503479A (enExample) |
| RU (1) | RU2201919C2 (enExample) |
| WO (1) | WO1999018068A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6548553B2 (en) | 1997-10-03 | 2003-04-15 | Temple University-Of The Commonwealth System Of Higher Education | Styryl sulfone anticancer agents |
| US6762207B1 (en) | 1999-04-02 | 2004-07-13 | Temple University - Of The Commonwealth System Of Higher Education | (E)-styryl sulfone anticancer agents |
| CA2366750C (en) * | 1999-04-02 | 2010-06-01 | Temple University - Of The Commonwealth System Of Higher Education | (e)-styryl sulfone anticancer agents |
| AU778825B2 (en) | 1999-06-16 | 2004-12-23 | Temple University - Of The Commonwealth System Of Higher Education | (Z)-styryl acetoxyphenyl sulfides as cyclooxygenase inhibitors |
| EP1223923B1 (en) * | 1999-10-12 | 2010-03-31 | Temple University of the Commonwealth System of Higher Education | Unsaturated aryl sulfones for protecting normal cells from cytotoxicity of chemotherapeutic agents |
| US6767926B1 (en) | 1999-10-12 | 2004-07-27 | Temple University - Of The Commonwealth System Of Higher Education | Method for protecting normal cells from cytotoxicity of chemotherapeutic agents |
| US6541475B2 (en) * | 2000-04-14 | 2003-04-01 | Temple University - Of The Commonwealth System Of Higher Education | α, β-unsaturated sulfones for treating proliferative disorders |
| US6486210B2 (en) * | 2000-04-14 | 2002-11-26 | Temple University—Of the Commonwealth System of Higher Education | Substituted styryl benzylsulfones for treating proliferative disorders |
| JP2004510761A (ja) * | 2000-10-05 | 2004-04-08 | 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 | 増殖性疾病を治療するための置換（ｅ）−スチリルベンジルスルホン |
| US6833480B2 (en) * | 2001-02-27 | 2004-12-21 | Temple University - Of The Commonwealth System Of Higher Education | (Z)-styrylbenzylsulfones and pharmaceutical uses thereof |
| WO2002069892A2 (en) * | 2001-02-28 | 2002-09-12 | Temple University Of The Commonwealth System Of Higher Education | METHOD FOR PROTECTING CELLS AND TISSUES FROM IONIZING RADIATION TOXICITY WITH α, β UNSATURATED ARYL SULFONES |
| EP1534284B1 (en) * | 2002-02-28 | 2011-07-27 | Temple University - Of The Commonwealth System of Higher Education | Amino-substituted sulfonanilides and derivatives thereof for treating proliferative disorders |
| ES2373945T3 (es) * | 2002-02-28 | 2012-02-10 | Temple University - Of The Commonwealth System Of Higher Education | Bencilsulfonas de (e)-2,6-dialcoxiestirilo amino sustituido sustituidas en 4 para tratar trastornos proliferativos. |
| US7012100B1 (en) | 2002-06-04 | 2006-03-14 | Avolix Pharmaceuticals, Inc. | Cell migration inhibiting compositions and methods and compositions for treating cancer |
| CA2546495C (en) * | 2003-11-14 | 2012-10-09 | Temple University - Of The Commonwealth System Of Higher Education | Alpha, beta-unsaturated sulfoxides for treating proliferative disorders |
| WO2005089269A2 (en) | 2004-03-16 | 2005-09-29 | Temple University - Of The Commonwealth System Of Higher Education | Substituted phenoxy- and phenylthio- derivatives for treating proliferative disorders |
| WO2006025924A2 (en) | 2004-06-24 | 2006-03-09 | Temple University Of The Commonwealth System Of Higher Education | Alpha, beta-unsaturated sulfones, sulfoxides, sulfonimides, sulfinimides, acylsulfonamides and acylsulfinamides and therapeutic uses thereof |
| CA2593523C (en) * | 2005-01-05 | 2014-04-08 | 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 |
| 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 |
| CA2663375A1 (en) * | 2006-09-15 | 2008-03-20 | Onconova Therapeutics, Inc. | Activated cytotoxic compounds for attachment to targeting molecules for the treatment of mammalian disease conditions |
| EP2091527B1 (en) * | 2006-12-13 | 2016-03-23 | Temple University - Of The Commonwealth System of Higher Education | Sulfide, sulfoxide and sulfone chalcone analogues, derivatives thereof and therapeutic uses thereof |
| ES2863538T3 (es) | 2012-09-20 | 2021-10-11 | Univ Temple | Derivados de alquil diarilo sustituidos, métodos de preparación y usos |
| ES2864681T3 (es) | 2012-12-07 | 2021-10-14 | Onconova Therapeutics Inc | Tratamiento del cáncer hematológico refractario a un agente contra el cáncer |
| WO2017023912A1 (en) | 2015-08-03 | 2017-02-09 | Temple University - Of The Commonwealth System Of Higher Education | 2,4,6-trialkoxystryl aryl sulfones, sulfonamides and carboxamides, and methods of preparation and use |
Family Cites Families (13)
| 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 |
| FR2645536B1 (fr) * | 1989-04-10 | 1991-05-31 | Rhone Poulenc Agrochimie | Composes herbicides et les compositions les contenant |
| US6177401B1 (en) * | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
| US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| US5659087A (en) | 1995-06-07 | 1997-08-19 | Eli Lilly And Company | Diarylvinyl sulfoxides |
| WO1996040629A1 (en) * | 1995-06-07 | 1996-12-19 | Sugen, Inc. | Tyrphostin-like compounds for the treatment of cell proliferative disorders or cell differentiation disorders |
-
1998
- 1998-10-01 IL IL13543898A patent/IL135438A/xx not_active IP Right Cessation
- 1998-10-01 CN CNB988098199A patent/CN1163480C/zh not_active Expired - Fee Related
- 1998-10-01 WO PCT/US1998/020580 patent/WO1999018068A1/en not_active Ceased
- 1998-10-01 CA CA002305790A patent/CA2305790C/en not_active Expired - Fee Related
- 1998-10-01 KR KR1020007003554A patent/KR100579355B1/ko not_active Expired - Fee Related
- 1998-10-01 US US09/509,227 patent/US6359013B1/en not_active Expired - Lifetime
- 1998-10-01 DE DE69828079T patent/DE69828079T2/de not_active Expired - Lifetime
- 1998-10-01 RU RU2000111513/04A patent/RU2201919C2/ru not_active IP Right Cessation
- 1998-10-01 BR BRPI9814059-0A patent/BR9814059B1/pt not_active IP Right Cessation
- 1998-10-01 EP EP98949680A patent/EP1027330B1/en not_active Expired - Lifetime
- 1998-10-01 AT AT98949680T patent/ATE284386T1/de not_active IP Right Cessation
- 1998-10-01 AU AU95954/98A patent/AU741042B2/en not_active Ceased
- 1998-10-01 JP JP2000514880A patent/JP4294217B2/ja not_active Expired - Fee Related
- 1998-10-01 NZ NZ503479A patent/NZ503479A/xx not_active IP Right Cessation
- 1998-10-01 CZ CZ20001174A patent/CZ299718B6/cs not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| BR9814059B1 (pt) | 2010-08-24 |
| HK1031373A1 (en) | 2001-06-15 |
| CZ20001174A3 (cs) | 2000-09-13 |
| EP1027330A1 (en) | 2000-08-16 |
| CZ299718B6 (cs) | 2008-10-29 |
| EP1027330B1 (en) | 2004-12-08 |
| KR100579355B1 (ko) | 2006-05-12 |
| JP4294217B2 (ja) | 2009-07-08 |
| WO1999018068A1 (en) | 1999-04-15 |
| CA2305790A1 (en) | 1999-04-15 |
| CN1273580A (zh) | 2000-11-15 |
| IL135438A0 (en) | 2001-05-20 |
| EP1027330A4 (en) | 2003-09-10 |
| DE69828079D1 (de) | 2005-01-13 |
| NZ503479A (en) | 2002-08-28 |
| RU2201919C2 (ru) | 2003-04-10 |
| BR9814059A (pt) | 2000-09-26 |
| AU9595498A (en) | 1999-04-27 |
| ATE284386T1 (de) | 2004-12-15 |
| KR20010015689A (ko) | 2001-02-26 |
| IL135438A (en) | 2005-12-18 |
| CA2305790C (en) | 2008-09-23 |
| US6359013B1 (en) | 2002-03-19 |
| AU741042B2 (en) | 2001-11-22 |
| JP2001519326A (ja) | 2001-10-23 |
| CN1163480C (zh) | 2004-08-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69828079T2 (de) | Styrolsulfone als antikrebsmittel | |
| DE60008098T2 (de) | Z-styryl sulfonen als anti-krebsmittel | |
| DE2616479C2 (de) | Substituierte Fluoracylresorcine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel und Kosmetika | |
| EP2842933A1 (de) | Mischungen cannabinoider Verbindungen, deren Herstellung und Verwendung | |
| EP0031954A2 (de) | Neue Sulfonamide, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel | |
| US6548553B2 (en) | Styryl sulfone anticancer agents | |
| DE69834109T2 (de) | 3-epi-vitamin d2 verbindungen und ihre anwendungen | |
| DE60020954T2 (de) | (e)-styrylsulfone als krebsbestreitende mittel | |
| DE69723463T2 (de) | Cyclische organoselenderivate, ihre herstellung und verwendung | |
| DE69623760T2 (de) | Kaliumionen-kanal-blocker | |
| DE2445811A1 (de) | Alkanolaminderivate | |
| DE60102925T2 (de) | Amino-thiolester-verbindungen, diese enthaltende pharmazeutische und kosmetische zusammensetzungen und ihre anwendungen | |
| EP0198277A1 (de) | Diselenobis-benzoesäureamide primärer und sekundärer Amine, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate | |
| WO2000059494A1 (en) | Styryl sulfone anticancer agents | |
| DE102006016367A1 (de) | Verwendung von Auronen für deren depigmentierende oder inhibierende Aktivität der Melanogenese in kosmetischen oder dermatologischen Zusammensetzungen | |
| DE69320030T2 (de) | Benzisoxazol-derivate und diese enthaltende pharmazeutische zusammensetzungen | |
| EP0002219B1 (de) | Arzneimittel mit schwefelhaltigen Estern und Verfahren zu ihrer Herstellung | |
| DE69509621T2 (de) | Diarylheptanoidderivat und diese enthaltende pharmazeutische Zusammensetzung | |
| DE69114922T2 (de) | Polysulfidverbindungen und Lipidperoxidierungsinhibitore, die diese Polysulfidverbindungen als aktive Zutaten enthalten. | |
| DE68910282T2 (de) | Acylaminoalkylpyridinamide als Inhibitoren der Tumormetastasierung. | |
| JP2012523391A (ja) | レゾルシノールの硫化誘導体、その製造及びその美容用途 | |
| DE2113489B2 (de) | 2-Nitro-benzofuranderivate, ein Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel | |
| DE3513070A1 (de) | Diselenobis-benzoesaeureamide primaerer amine, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate | |
| DE2528025A1 (de) | Heilmittel und verfahren zu seiner herstellung | |
| SU799628A3 (ru) | Гербицидный состав |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |