CA2368653C - Z-styryl sulfone anticancer agents - Google Patents
Z-styryl sulfone anticancer agents Download PDFInfo
- Publication number
- CA2368653C CA2368653C CA002368653A CA2368653A CA2368653C CA 2368653 C CA2368653 C CA 2368653C CA 002368653 A CA002368653 A CA 002368653A CA 2368653 A CA2368653 A CA 2368653A CA 2368653 C CA2368653 C CA 2368653C
- Authority
- CA
- Canada
- Prior art keywords
- hydrogen
- chloro
- compound
- bromo
- fluoro
- 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 - Fee Related
Links
- 239000002246 antineoplastic agent Substances 0.000 title abstract description 4
- XJNHONCWGODPIZ-XSYHWHKQSA-N C=1C=CC=CC=1\C=C/S(=O)(=O)\C=C/C1=CC=CC=C1 Chemical compound C=1C=CC=CC=1\C=C/S(=O)(=O)\C=C/C1=CC=CC=C1 XJNHONCWGODPIZ-XSYHWHKQSA-N 0.000 title description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 108
- 239000001257 hydrogen Substances 0.000 claims abstract description 90
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 44
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 27
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 26
- -1 chloro, bromo, iodo Chemical group 0.000 claims abstract description 25
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims description 84
- 150000002431 hydrogen Chemical group 0.000 claims description 41
- 125000001246 bromo group Chemical group Br* 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 210000004881 tumor cell Anatomy 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 201000011510 cancer Diseases 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 230000006907 apoptotic process Effects 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 125000002346 iodo group Chemical group I* 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 6
- 230000002611 ovarian Effects 0.000 claims description 6
- 230000002062 proliferating effect Effects 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- JJSHRTVHJFKOFB-KTKRTIGZSA-N 1-[[(z)-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-KTKRTIGZSA-N 0.000 claims description 3
- URBLDUHDENNTET-KTKRTIGZSA-N 1-[[(z)-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-KTKRTIGZSA-N 0.000 claims description 3
- XMPVUPXPMAUISH-KTKRTIGZSA-N 1-[[(z)-2-(4-chlorophenyl)ethenyl]sulfonylmethyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1CS(=O)(=O)\C=C/C1=CC=C(Cl)C=C1 XMPVUPXPMAUISH-KTKRTIGZSA-N 0.000 claims description 3
- SFEOZCOEUPNEJG-KTKRTIGZSA-N 1-[[(z)-2-(4-fluorophenyl)ethenyl]sulfonylmethyl]-4-iodobenzene Chemical compound C1=CC(F)=CC=C1\C=C/S(=O)(=O)CC1=CC=C(I)C=C1 SFEOZCOEUPNEJG-KTKRTIGZSA-N 0.000 claims description 3
- WXVZZCHUAIGQKJ-KTKRTIGZSA-N 1-chloro-4-[[(z)-2-(4-chlorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(Cl)=CC=C1CS(=O)(=O)\C=C/C1=CC=C(Cl)C=C1 WXVZZCHUAIGQKJ-KTKRTIGZSA-N 0.000 claims description 3
- GMKXPTFOBQFAOD-KTKRTIGZSA-N 1-chloro-4-[[(z)-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-KTKRTIGZSA-N 0.000 claims description 3
- QFXKVNVCBJMHBH-KTKRTIGZSA-N 1-fluoro-4-[[(z)-2-(4-fluorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(F)=CC=C1CS(=O)(=O)\C=C/C1=CC=C(F)C=C1 QFXKVNVCBJMHBH-KTKRTIGZSA-N 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 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 abstract 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 abstract description 8
- 239000000543 intermediate Substances 0.000 abstract description 8
- 238000002360 preparation method Methods 0.000 abstract description 4
- 238000000034 method Methods 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 31
- 239000000243 solution Substances 0.000 description 26
- 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 22
- 125000004429 atom Chemical group 0.000 description 22
- 230000003647 oxidation Effects 0.000 description 22
- 238000007254 oxidation reaction Methods 0.000 description 22
- 239000011734 sodium Substances 0.000 description 22
- 229910052708 sodium Inorganic materials 0.000 description 22
- 101150041968 CDC13 gene Proteins 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 125000003118 aryl group Chemical group 0.000 description 20
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 10
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 10
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 10
- 102000019145 JUN kinase activity proteins 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 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
- WWFIIZLHSNBNTC-UHFFFAOYSA-N (2-chlorophenyl)methanethiol Chemical compound SCC1=CC=CC=C1Cl WWFIIZLHSNBNTC-UHFFFAOYSA-N 0.000 description 5
- GKQXPTHQTXCXEV-UHFFFAOYSA-N (4-chlorophenyl)methanethiol Chemical compound SCC1=CC=C(Cl)C=C1 GKQXPTHQTXCXEV-UHFFFAOYSA-N 0.000 description 5
- RKTRHMNWVZRZJQ-UHFFFAOYSA-N (4-fluorophenyl)methanethiol Chemical compound FC1=CC=C(CS)C=C1 RKTRHMNWVZRZJQ-UHFFFAOYSA-N 0.000 description 5
- QXSWHQGIEKUBAS-UHFFFAOYSA-N 1-ethynyl-4-fluorobenzene Chemical group FC1=CC=C(C#C)C=C1 QXSWHQGIEKUBAS-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- LTLVZQZDXQWLHU-UHFFFAOYSA-N 1-bromo-4-ethynylbenzene Chemical group BrC1=CC=C(C#C)C=C1 LTLVZQZDXQWLHU-UHFFFAOYSA-N 0.000 description 4
- LFZJRTMTKGYJRS-UHFFFAOYSA-N 1-chloro-4-ethynylbenzene Chemical group ClC1=CC=C(C#C)C=C1 LFZJRTMTKGYJRS-UHFFFAOYSA-N 0.000 description 4
- KSZVOXHGCKKOLL-UHFFFAOYSA-N 4-Ethynyltoluene Chemical group CC1=CC=C(C#C)C=C1 KSZVOXHGCKKOLL-UHFFFAOYSA-N 0.000 description 4
- 208000032612 Glial tumor Diseases 0.000 description 4
- 206010018338 Glioma Diseases 0.000 description 4
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 4
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 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
- 230000004913 activation 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
- 102000015694 estrogen receptors Human genes 0.000 description 3
- 108010038795 estrogen receptors Proteins 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 208000023958 prostate neoplasm Diseases 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 230000004668 G2/M phase Effects 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
- 108091000080 Phosphotransferase Proteins 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
- 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
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000003064 anti-oxidating effect Effects 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003834 intracellular effect Effects 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
- 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
- 230000000865 phosphorylative effect Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000000770 proinflammatory effect 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
- 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
- 150000003839 salts Chemical class 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 230000001225 therapeutic effect 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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 1
- OIMBYDFUXNAJSV-UHFFFAOYSA-N (4-iodophenyl)methanethiol Chemical compound SCC1=CC=C(I)C=C1 OIMBYDFUXNAJSV-UHFFFAOYSA-N 0.000 description 1
- APMAVVWPSUJNPP-FDWQPRGYSA-N 1-[(z)-1-[(z)-1,3-bis(4-chlorophenyl)prop-2-enyl]sulfanyl-3-(4-chlorophenyl)prop-2-enyl]-4-chlorobenzene Chemical compound C1=CC(Cl)=CC=C1\C=C/C(C=1C=CC(Cl)=CC=1)SC(C=1C=CC(Cl)=CC=1)\C=C/C1=CC=C(Cl)C=C1 APMAVVWPSUJNPP-FDWQPRGYSA-N 0.000 description 1
- OVCQWNRQZMILRV-FDWQPRGYSA-N 1-[(z)-1-[(z)-1,3-bis(4-fluorophenyl)prop-2-enyl]sulfanyl-3-(4-fluorophenyl)prop-2-enyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1\C=C/C(C=1C=CC(F)=CC=1)SC(C=1C=CC(F)=CC=1)\C=C/C1=CC=C(F)C=C1 OVCQWNRQZMILRV-FDWQPRGYSA-N 0.000 description 1
- PBRXGHNUKOXERA-KHPPLWFESA-N 1-[(z)-2-[(4-chlorophenyl)methylsulfonyl]ethenyl]-4-methylbenzene Chemical compound C1=CC(C)=CC=C1\C=C/S(=O)(=O)CC1=CC=C(Cl)C=C1 PBRXGHNUKOXERA-KHPPLWFESA-N 0.000 description 1
- UKBYVJCGADOQNV-KHPPLWFESA-N 1-[(z)-2-[(4-fluorophenyl)methylsulfonyl]ethenyl]-4-methylbenzene Chemical compound C1=CC(C)=CC=C1\C=C/S(=O)(=O)CC1=CC=C(F)C=C1 UKBYVJCGADOQNV-KHPPLWFESA-N 0.000 description 1
- YTFTUAAHDSAPCD-KHPPLWFESA-N 1-[(z)-2-benzylsulfonylethenyl]-4-bromobenzene Chemical compound C1=CC(Br)=CC=C1\C=C/S(=O)(=O)CC1=CC=CC=C1 YTFTUAAHDSAPCD-KHPPLWFESA-N 0.000 description 1
- CQQMYELYPHEXMW-KHPPLWFESA-N 1-[(z)-2-benzylsulfonylethenyl]-4-chlorobenzene Chemical compound C1=CC(Cl)=CC=C1\C=C/S(=O)(=O)CC1=CC=CC=C1 CQQMYELYPHEXMW-KHPPLWFESA-N 0.000 description 1
- CJZVNSBEGOPYSR-KHPPLWFESA-N 1-[(z)-2-benzylsulfonylethenyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1\C=C/S(=O)(=O)CC1=CC=CC=C1 CJZVNSBEGOPYSR-KHPPLWFESA-N 0.000 description 1
- CYONJZNVDFMCRO-QXMHVHEDSA-N 1-[(z)-2-benzylsulfonylethenyl]-4-methylbenzene Chemical compound C1=CC(C)=CC=C1\C=C/S(=O)(=O)CC1=CC=CC=C1 CYONJZNVDFMCRO-QXMHVHEDSA-N 0.000 description 1
- FNTIBJYLBWLPMH-KTKRTIGZSA-N 1-[[(z)-2-(4-bromophenyl)ethenyl]sulfonylmethyl]-2-chlorobenzene Chemical compound ClC1=CC=CC=C1CS(=O)(=O)\C=C/C1=CC=C(Br)C=C1 FNTIBJYLBWLPMH-KTKRTIGZSA-N 0.000 description 1
- GETOKRNJABIKLG-KTKRTIGZSA-N 1-bromo-4-[(z)-2-[(4-fluorophenyl)methylsulfanyl]ethenyl]benzene Chemical compound C1=CC(F)=CC=C1CS\C=C/C1=CC=C(Br)C=C1 GETOKRNJABIKLG-KTKRTIGZSA-N 0.000 description 1
- UDOLHGWNCYGJOJ-AXPXABNXSA-N 1-bromo-4-[(z)-3-[(z)-3-(4-bromophenyl)-1-(2-chlorophenyl)prop-2-enyl]sulfanyl-3-(2-chlorophenyl)prop-1-enyl]benzene Chemical compound ClC1=CC=CC=C1C(\C=C/C=1C=CC(Br)=CC=1)SC(C=1C(=CC=CC=1)Cl)\C=C/C1=CC=C(Br)C=C1 UDOLHGWNCYGJOJ-AXPXABNXSA-N 0.000 description 1
- QJDPTWVRQRAUQD-FDWQPRGYSA-N 1-bromo-4-[(z)-3-[(z)-3-(4-bromophenyl)-1-(4-chlorophenyl)prop-2-enyl]sulfanyl-3-(4-chlorophenyl)prop-1-enyl]benzene Chemical compound C1=CC(Cl)=CC=C1C(\C=C/C=1C=CC(Br)=CC=1)SC(C=1C=CC(Cl)=CC=1)\C=C/C1=CC=C(Br)C=C1 QJDPTWVRQRAUQD-FDWQPRGYSA-N 0.000 description 1
- ZUAQRWGGTKGIQI-BMJUYKDLSA-N 1-bromo-4-[(z)-3-[(z)-3-(4-bromophenyl)-1-phenylprop-2-enyl]sulfanyl-3-phenylprop-1-enyl]benzene Chemical compound C1=CC(Br)=CC=C1\C=C/C(C=1C=CC=CC=1)SC(C=1C=CC=CC=1)\C=C/C1=CC=C(Br)C=C1 ZUAQRWGGTKGIQI-BMJUYKDLSA-N 0.000 description 1
- SQBMIVFIRPQMSA-WRBBJXAJSA-N 1-chloro-2-[(z)-1-[(z)-1-(2-chlorophenyl)-3-(4-methylphenyl)prop-2-enyl]sulfanyl-3-(4-methylphenyl)prop-2-enyl]benzene Chemical compound C1=CC(C)=CC=C1\C=C/C(C=1C(=CC=CC=1)Cl)SC(C=1C(=CC=CC=1)Cl)\C=C/C1=CC=C(C)C=C1 SQBMIVFIRPQMSA-WRBBJXAJSA-N 0.000 description 1
- VWROXZHTGGUEDO-AXPXABNXSA-N 1-chloro-2-[(z)-3-(4-chlorophenyl)-1-[(z)-1-(2-chlorophenyl)-3-(4-chlorophenyl)prop-2-enyl]sulfanylprop-2-enyl]benzene Chemical compound C1=CC(Cl)=CC=C1\C=C/C(C=1C(=CC=CC=1)Cl)SC(C=1C(=CC=CC=1)Cl)\C=C/C1=CC=C(Cl)C=C1 VWROXZHTGGUEDO-AXPXABNXSA-N 0.000 description 1
- AXPPSPUVIWKNPV-KHPPLWFESA-N 1-chloro-2-[[(Z)-2-phenylethenyl]sulfanylmethyl]benzene Chemical compound ClC1=CC=CC=C1CS\C=C/C1=CC=CC=C1 AXPPSPUVIWKNPV-KHPPLWFESA-N 0.000 description 1
- OPBMQZXCAHCREC-KHPPLWFESA-N 1-chloro-2-[[(Z)-2-phenylethenyl]sulfonylmethyl]benzene Chemical compound ClC1=CC=CC=C1CS(=O)(=O)\C=C/C1=CC=CC=C1 OPBMQZXCAHCREC-KHPPLWFESA-N 0.000 description 1
- MCFADXZMMSICDD-KTKRTIGZSA-N 1-chloro-2-[[(z)-2-(4-chlorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(Cl)=CC=C1\C=C/S(=O)(=O)CC1=CC=CC=C1Cl MCFADXZMMSICDD-KTKRTIGZSA-N 0.000 description 1
- UQHISZNGJQQLPQ-KTKRTIGZSA-N 1-chloro-2-[[(z)-2-(4-fluorophenyl)ethenyl]sulfanylmethyl]benzene Chemical compound C1=CC(F)=CC=C1\C=C/SCC1=CC=CC=C1Cl UQHISZNGJQQLPQ-KTKRTIGZSA-N 0.000 description 1
- YJSWYJYDZJZNPQ-KTKRTIGZSA-N 1-chloro-2-[[(z)-2-(4-fluorophenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(F)=CC=C1\C=C/S(=O)(=O)CC1=CC=CC=C1Cl YJSWYJYDZJZNPQ-KTKRTIGZSA-N 0.000 description 1
- VQHFZEXWUQNBDL-KHPPLWFESA-N 1-chloro-2-[[(z)-2-(4-methylphenyl)ethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(C)=CC=C1\C=C/S(=O)(=O)CC1=CC=CC=C1Cl VQHFZEXWUQNBDL-KHPPLWFESA-N 0.000 description 1
- KNYVJCGWVZBQKJ-FDWQPRGYSA-N 1-chloro-4-[(z)-1-[(z)-1-(4-chlorophenyl)-3-(4-fluorophenyl)prop-2-enyl]sulfanyl-3-(4-fluorophenyl)prop-2-enyl]benzene Chemical compound C1=CC(F)=CC=C1\C=C/C(C=1C=CC(Cl)=CC=1)SC(C=1C=CC(Cl)=CC=1)\C=C/C1=CC=C(F)C=C1 KNYVJCGWVZBQKJ-FDWQPRGYSA-N 0.000 description 1
- CTQJDJGSRQEWFU-IINORCHSSA-N 1-chloro-4-[(z)-1-[(z)-1-(4-chlorophenyl)-3-(4-methylphenyl)prop-2-enyl]sulfanyl-3-(4-methylphenyl)prop-2-enyl]benzene Chemical compound C1=CC(C)=CC=C1\C=C/C(C=1C=CC(Cl)=CC=1)SC(C=1C=CC(Cl)=CC=1)\C=C/C1=CC=C(C)C=C1 CTQJDJGSRQEWFU-IINORCHSSA-N 0.000 description 1
- GWGPKZYCSNGPJJ-FDWQPRGYSA-N 1-chloro-4-[(z)-3-[(z)-3-(4-chlorophenyl)-1-(4-fluorophenyl)prop-2-enyl]sulfanyl-3-(4-fluorophenyl)prop-1-enyl]benzene Chemical compound C1=CC(F)=CC=C1C(\C=C/C=1C=CC(Cl)=CC=1)SC(C=1C=CC(F)=CC=1)\C=C/C1=CC=C(Cl)C=C1 GWGPKZYCSNGPJJ-FDWQPRGYSA-N 0.000 description 1
- ZFWBVVZJPKJQKX-BMJUYKDLSA-N 1-chloro-4-[(z)-3-[(z)-3-(4-chlorophenyl)-1-phenylprop-2-enyl]sulfanyl-3-phenylprop-1-enyl]benzene Chemical compound C1=CC(Cl)=CC=C1\C=C/C(C=1C=CC=CC=1)SC(C=1C=CC=CC=1)\C=C/C1=CC=C(Cl)C=C1 ZFWBVVZJPKJQKX-BMJUYKDLSA-N 0.000 description 1
- QNXZQUAYPIPJMQ-KHPPLWFESA-N 1-chloro-4-[[(Z)-2-phenylethenyl]sulfanylmethyl]benzene Chemical compound C1=CC(Cl)=CC=C1CS\C=C/C1=CC=CC=C1 QNXZQUAYPIPJMQ-KHPPLWFESA-N 0.000 description 1
- VCTUJHZNTIOIPW-KHPPLWFESA-N 1-chloro-4-[[(Z)-2-phenylethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(Cl)=CC=C1CS(=O)(=O)\C=C/C1=CC=CC=C1 VCTUJHZNTIOIPW-KHPPLWFESA-N 0.000 description 1
- LVTXGKZGJWJLFC-IINORCHSSA-N 1-fluoro-4-[(z)-1-[(z)-1-(4-fluorophenyl)-3-(4-methylphenyl)prop-2-enyl]sulfanyl-3-(4-methylphenyl)prop-2-enyl]benzene Chemical compound C1=CC(C)=CC=C1\C=C/C(C=1C=CC(F)=CC=1)SC(C=1C=CC(F)=CC=1)\C=C/C1=CC=C(C)C=C1 LVTXGKZGJWJLFC-IINORCHSSA-N 0.000 description 1
- LWWWNBINKVURMF-KTKRTIGZSA-N 1-fluoro-4-[(z)-2-[(4-iodophenyl)methylsulfanyl]ethenyl]benzene Chemical compound C1=CC(F)=CC=C1\C=C/SCC1=CC=C(I)C=C1 LWWWNBINKVURMF-KTKRTIGZSA-N 0.000 description 1
- QQSFDKBZTYVAPX-BMJUYKDLSA-N 1-fluoro-4-[(z)-3-[(z)-3-(4-fluorophenyl)-1-phenylprop-2-enyl]sulfanyl-3-phenylprop-1-enyl]benzene Chemical compound C1=CC(F)=CC=C1\C=C/C(C=1C=CC=CC=1)SC(C=1C=CC=CC=1)\C=C/C1=CC=C(F)C=C1 QQSFDKBZTYVAPX-BMJUYKDLSA-N 0.000 description 1
- VUDDPYWCQOAKKC-KHPPLWFESA-N 1-fluoro-4-[[(Z)-2-phenylethenyl]sulfanylmethyl]benzene Chemical compound C1=CC(F)=CC=C1CS\C=C/C1=CC=CC=C1 VUDDPYWCQOAKKC-KHPPLWFESA-N 0.000 description 1
- LIJWFKOGPDQHRW-KHPPLWFESA-N 1-fluoro-4-[[(z)-2-phenylethenyl]sulfonylmethyl]benzene Chemical compound C1=CC(F)=CC=C1CS(=O)(=O)\C=C/C1=CC=CC=C1 LIJWFKOGPDQHRW-KHPPLWFESA-N 0.000 description 1
- MFCMVMBOUSYNIF-SXAUZNKPSA-N 1-methyl-4-[(z)-3-[(z)-3-(4-methylphenyl)-1-phenylprop-2-enyl]sulfanyl-3-phenylprop-1-enyl]benzene Chemical compound C1=CC(C)=CC=C1\C=C/C(C=1C=CC=CC=1)SC(C=1C=CC=CC=1)\C=C/C1=CC=C(C)C=C1 MFCMVMBOUSYNIF-SXAUZNKPSA-N 0.000 description 1
- 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 1
- 101100397594 Ancylostoma caninum JNK-1 gene 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
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 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
- 241001529936 Murinae Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000001253 Protein Kinase 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-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
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 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 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 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
- 230000033228 biological regulation Effects 0.000 description 1
- 208000016738 bone Paget disease Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000011803 breast fibrocystic disease Diseases 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 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
- 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
- 208000011379 keloid formation Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 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
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 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
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation 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
- 210000005267 prostate cell Anatomy 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
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 201000008628 secondary progressive multiple sclerosis Diseases 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
- 159000000000 sodium salts Chemical class 0.000 description 1
- SNCHEDBJOUWPMJ-UHFFFAOYSA-M sodium;phenylmethanethiolate Chemical class [Na+].[S-]CC1=CC=CC=C1 SNCHEDBJOUWPMJ-UHFFFAOYSA-M 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
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 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
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 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
- 230000004614 tumor growth 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
- C07C321/12—Sulfides, hydropolysulfides, or polysulfides having thio groups bound to acyclic carbon atoms
- C07C321/20—Sulfides, hydropolysulfides, or polysulfides having thio 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
- C07C317/02—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
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/01—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 halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton
- C07C323/02—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 halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/07—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 halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/282,855 | 1999-03-31 | ||
| US09/282,855 US6201154B1 (en) | 1999-03-31 | 1999-03-31 | Z-styryl sulfone anticancer agents |
| PCT/US2000/008350 WO2000057872A1 (en) | 1999-03-31 | 2000-03-30 | Z-styryl sulfone anticancer agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2368653A1 CA2368653A1 (en) | 2000-10-05 |
| CA2368653C true CA2368653C (en) | 2010-01-12 |
Family
ID=23083418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002368653A Expired - Fee Related CA2368653C (en) | 1999-03-31 | 2000-03-30 | Z-styryl sulfone anticancer agents |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US6201154B1 (https=) |
| EP (1) | EP1180024B1 (https=) |
| JP (1) | JP4468593B2 (https=) |
| AT (1) | ATE258790T1 (https=) |
| AU (1) | AU771133B2 (https=) |
| CA (1) | CA2368653C (https=) |
| DE (1) | DE60008098T2 (https=) |
| WO (1) | WO2000057872A1 (https=) |
Families Citing this family (19)
| 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 |
| EP1173160B1 (en) * | 1999-04-02 | 2005-06-22 | Temple University of the Commonwealth System of Higher Education | (e)-styryl sulfone anticancer 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 |
| WO2002028828A1 (en) * | 2000-10-05 | 2002-04-11 | Temple University - Of The Commonwealth System Of Higher Education | Substituted (e)-styryl benzylsulfones for treating proliferative disorders |
| JP2004521126A (ja) * | 2001-02-27 | 2004-07-15 | 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 | （ｚ）−スチリルベンジルスルホン及びそれらの医薬としての使用 |
| AU2002305942B2 (en) * | 2001-02-28 | 2006-10-26 | Onconova Therapeutics, Inc. | Method for protecting cells and tissues from ionizing radiation toxicity with Alpha, Beta unsaturated aryl sulfones |
| US20060270643A1 (en) * | 2002-10-31 | 2006-11-30 | Chawnshang Chang | Hyfroxyflutamide induced pathways related to androgen receptor negative prostate cancer cells |
| JP5196787B2 (ja) * | 2003-11-14 | 2013-05-15 | 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 | 増殖性疾患を治療するためのα，β−不飽和スルホキシド |
| KR101274524B1 (ko) * | 2004-03-16 | 2013-06-19 | 온코노바 테라퓨틱스, 인코포레이티드 | 증식성 질병 치료용 치환 페녹시- 및 페닐티오- 유도체 |
| EP1773310B9 (en) | 2004-06-24 | 2012-04-25 | Temple University - Of The Commonwealth System of Higher Education | Alpha, beta-unsaturated sulfones, sulfoxides, sulfonimides, sulfinimides, acylsulfonamides and acylsulfinamides and therapeutic uses thereof |
| AU2006216544B2 (en) * | 2005-02-25 | 2012-04-05 | Onconova Therapeutics, Inc. | Unsaturated sulfides, sulfones, sulfoxides and sulfonamides synthesis |
| 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 |
| US8308342B2 (en) * | 2008-11-24 | 2012-11-13 | Kraft Foods Global Brands Llc | Processing elements for mixing meat products |
| GB201010359D0 (en) | 2010-06-21 | 2010-08-04 | Univ Nottingham | Compounds for treating proliferative disorders |
| KR101992929B1 (ko) | 2012-09-20 | 2019-06-25 | 템플 유니버시티-오브 더 커먼웰쓰 시스템 오브 하이어 에듀케이션 | 치환된 알킬 디아릴 유도체, 제조방법 및 용도 |
| 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 |
Family Cites Families (11)
| 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 |
| US3463774A (en) | 1963-03-18 | 1969-08-26 | Hoffmann La Roche | Novel 4,1-benzothiazepin-2-(1h)-ones and 4,1-benzothiazepines |
| 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 |
| US5659087A (en) | 1995-06-07 | 1997-08-19 | Eli Lilly And Company | Diarylvinyl sulfoxides |
| US5733909A (en) * | 1996-02-01 | 1998-03-31 | Merck Frosst Canada, Inc. | Diphenyl stilbenes as prodrugs to COX-2 inhibitors |
-
1999
- 1999-03-31 US US09/282,855 patent/US6201154B1/en not_active Expired - Lifetime
-
2000
- 2000-03-30 JP JP2000607623A patent/JP4468593B2/ja not_active Expired - Fee Related
- 2000-03-30 US US09/937,805 patent/US6576675B1/en not_active Expired - Lifetime
- 2000-03-30 AT AT00919829T patent/ATE258790T1/de not_active IP Right Cessation
- 2000-03-30 AU AU40450/00A patent/AU771133B2/en not_active Ceased
- 2000-03-30 CA CA002368653A patent/CA2368653C/en not_active Expired - Fee Related
- 2000-03-30 WO PCT/US2000/008350 patent/WO2000057872A1/en not_active Ceased
- 2000-03-30 DE DE60008098T patent/DE60008098T2/de not_active Expired - Lifetime
- 2000-03-30 EP EP00919829A patent/EP1180024B1/en not_active Expired - Lifetime
- 2000-11-22 US US09/722,450 patent/US6414034B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1180024A4 (en) | 2002-06-19 |
| JP2002540152A (ja) | 2002-11-26 |
| JP4468593B2 (ja) | 2010-05-26 |
| US6576675B1 (en) | 2003-06-10 |
| EP1180024B1 (en) | 2004-02-04 |
| US6414034B1 (en) | 2002-07-02 |
| CA2368653A1 (en) | 2000-10-05 |
| DE60008098D1 (de) | 2004-03-11 |
| AU4045000A (en) | 2000-10-16 |
| AU771133B2 (en) | 2004-03-11 |
| DE60008098T2 (de) | 2005-10-27 |
| US6201154B1 (en) | 2001-03-13 |
| EP1180024A1 (en) | 2002-02-20 |
| ATE258790T1 (de) | 2004-02-15 |
| WO2000057872A1 (en) | 2000-10-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2368653C (en) | Z-styryl sulfone anticancer agents | |
| JP4294217B2 (ja) | スチリルスルホン抗癌剤 | |
| US6642410B2 (en) | Substituted benzylthioacetic acids and esters | |
| US6548553B2 (en) | Styryl sulfone anticancer agents | |
| AU2001251615A1 (en) | Substituted styryl benzylsulfones for treating proliferative disorders | |
| US6762207B1 (en) | (E)-styryl sulfone anticancer agents | |
| US6541475B2 (en) | α, β-unsaturated sulfones for treating proliferative disorders | |
| EP1173160B1 (en) | (e)-styryl sulfone anticancer agents | |
| WO2000059494A1 (en) | Styryl sulfone anticancer agents | |
| HK1031373B (en) | Styryl sulfone anticancer agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20190401 |