IL91452A - Beta-carbolines,their bioisosteric benzofuran and benzothiophene analogues,their preparation and cytostatic compositions containing them - Google Patents
Beta-carbolines,their bioisosteric benzofuran and benzothiophene analogues,their preparation and cytostatic compositions containing themInfo
- Publication number
- IL91452A IL91452A IL9145289A IL9145289A IL91452A IL 91452 A IL91452 A IL 91452A IL 9145289 A IL9145289 A IL 9145289A IL 9145289 A IL9145289 A IL 9145289A IL 91452 A IL91452 A IL 91452A
- Authority
- IL
- Israel
- Prior art keywords
- group
- atoms
- hydrogen
- formula
- compound
- Prior art date
Links
- 230000001085 cytostatic effect Effects 0.000 title claims abstract description 7
- 239000000203 mixture Substances 0.000 title claims description 12
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 6
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title abstract description 4
- 239000000824 cytostatic agent Substances 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
- 239000001257 hydrogen Substances 0.000 claims abstract description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 239000001301 oxygen Substances 0.000 claims abstract description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000005864 Sulphur Substances 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- 125000006413 ring segment Chemical group 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract 6
- 238000000034 method Methods 0.000 claims description 13
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 2
- 238000006407 Bischler-Napieralski reaction Methods 0.000 claims 1
- 238000006929 Pictet-Spengler synthesis reaction Methods 0.000 claims 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
- 229940099990 ogen Drugs 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 2
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 abstract description 2
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- -1 for example Chemical class 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229930182478 glucoside Natural products 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 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
- 150000008131 glucosides Chemical class 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- VFZRZRDOXPRTSC-UHFFFAOYSA-N 3,5-Dimethoxybenzaldehyde Chemical compound COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 101150052863 THY1 gene Proteins 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000003021 clonogenic effect Effects 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 101000904970 Arabidopsis thaliana Histone H2B.7 Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 101100178983 Caenorhabditis elegans hyl-1 gene Proteins 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 101100260565 Dictyostelium discoideum thyA gene Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241001632427 Radiola Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 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
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- DABYEOZXRSTEGL-NSHDSACASA-N ethyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical group C1=CC=C2C(C[C@H](N)C(=O)OCC)=CNC2=C1 DABYEOZXRSTEGL-NSHDSACASA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- MLGCXEBRWGEOQX-UHFFFAOYSA-N tetradifon Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C1=CC(Cl)=C(Cl)C=C1Cl MLGCXEBRWGEOQX-UHFFFAOYSA-N 0.000 description 1
- 101150068774 thyX gene Proteins 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D515/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Saccharide Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL8802123 | 1988-08-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL91452A0 IL91452A0 (en) | 1990-04-29 |
| IL91452A true IL91452A (en) | 1994-05-30 |
Family
ID=19852815
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9145289A IL91452A (en) | 1988-08-29 | 1989-08-28 | Beta-carbolines,their bioisosteric benzofuran and benzothiophene analogues,their preparation and cytostatic compositions containing them |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5095020A (da) |
| EP (1) | EP0357122A3 (da) |
| JP (1) | JPH02111772A (da) |
| AU (1) | AU625068B2 (da) |
| CA (1) | CA1337200C (da) |
| DK (1) | DK417289A (da) |
| IL (1) | IL91452A (da) |
| NZ (1) | NZ230431A (da) |
| ZA (1) | ZA896473B (da) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE136032T1 (de) * | 1987-07-20 | 1996-04-15 | Duphar Int Res | 8,9-anellierte 1,2,3,4-tetrahydro-beta-carbolin- derivate |
| EP0347980A1 (en) * | 1988-06-20 | 1989-12-27 | Duphar International Research B.V | 8,9-Annelated beta-carbolines and 8,9-anelated-3,4-dihydro-beta-carbolines |
| EP0380155A1 (en) * | 1989-01-19 | 1990-08-01 | Duphar International Research B.V | 8,9-Annelated-1,2,3,4-tetrahydro-beta-carboline derivatives |
| US5622960A (en) * | 1992-04-14 | 1997-04-22 | The United States Of America As Represented By The Department Of Health And Human Services | Topoisomerase II inhibitors and therapeutic uses therefor |
| GB9401090D0 (en) * | 1994-01-21 | 1994-03-16 | Glaxo Lab Sa | Chemical compounds |
| GB9514465D0 (en) * | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Chemical compounds |
| US6143746A (en) * | 1994-01-21 | 2000-11-07 | Icos Corporation | Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use |
| GB9514464D0 (en) | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Medicaments |
| GB9514473D0 (en) * | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Chemical compounds |
| YU49898A (sh) | 1996-05-10 | 2000-03-21 | Icos Corporation | Hemijska jedinjenja |
| DE19744257B4 (de) * | 1997-10-07 | 2004-04-15 | Zentaris Gmbh | Beta-Carboline und deren Verwendung zur Behandlung von malignen und anderen, auf pathologischen Zellproliferationen beruhenden Erkrankungen |
| WO2002028865A2 (en) * | 2000-10-03 | 2002-04-11 | Lilly Icos Llc | Condensed pyridoindole derivatives |
| TWI329111B (en) | 2002-05-24 | 2010-08-21 | X Ceptor Therapeutics Inc | Azepinoindole and pyridoindole derivatives as pharmaceutical agents |
| US7872133B2 (en) * | 2003-06-23 | 2011-01-18 | Ono Pharmaceutical Co., Ltd. | Tricyclic heterocycle compound |
| AU2005206570A1 (en) * | 2004-01-23 | 2005-08-04 | Novartis Vaccines And Diagnostics, Inc. | Tetrahydrocarboline compounds as anticancer agents |
| US8076352B2 (en) | 2004-03-15 | 2011-12-13 | Ptc Therapeutics, Inc. | Administration of carboline derivatives useful in the treatment of cancer and other diseases |
| US7767689B2 (en) | 2004-03-15 | 2010-08-03 | Ptc Therapeutics, Inc. | Carboline derivatives useful in the treatment of cancer |
| SG184755A1 (en) | 2004-03-15 | 2012-10-30 | Ptc Therapeutics Inc | Carboline derivatives useful in the inhibition of angiogenesis |
| US8076353B2 (en) | 2004-03-15 | 2011-12-13 | Ptc Therapeutics, Inc. | Inhibition of VEGF translation |
| AU2005273867B2 (en) * | 2004-08-18 | 2010-12-23 | 4Sc Ag | Benzothienopyridines for use as inhibitors of Eg5 kinesin |
| WO2006068164A1 (ja) * | 2004-12-22 | 2006-06-29 | Ono Pharmaceutical Co., Ltd. | 三環式化合物およびその用途 |
| US20080114017A1 (en) * | 2005-01-27 | 2008-05-15 | Matthias Vennemann | Novel Indolopyridines, Benzofuranopyridines and Benzothienopyridines |
| JP2008528551A (ja) * | 2005-01-28 | 2008-07-31 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | インドロピリジン、ベンゾフラノピリジン及びベンゾチエノピリジン |
| US8530493B2 (en) | 2006-02-22 | 2013-09-10 | 4Sc Ag | Indolopyridines as Eg5 kinesin modulators |
| FR2914924A1 (fr) * | 2007-04-13 | 2008-10-17 | Fourtillan Snc | Derives de 4,5,11,11a-tetrahydro-1h,6h-oxazolo[3',4': 1,6] pyrido[3,4-b]indol-3-one et leur utilisation en therapeutique. |
| CA3080983C (en) | 2009-05-27 | 2023-02-28 | Pct Therapeutics, Inc. | Method of inhibiting and reducing a viral infection |
| CN102459263A (zh) | 2009-05-27 | 2012-05-16 | Ptc医疗公司 | 取代的四氢β-咔啉的制备工艺 |
| US8697662B2 (en) | 2009-05-27 | 2014-04-15 | Ptc Therapeutics, Inc. | Methods for treating Kaposi sarcoma |
| WO2010138685A1 (en) | 2009-05-27 | 2010-12-02 | Ptc Therapeutics, Inc. | Methods for treating prostate conditions |
| US9168247B2 (en) | 2010-06-25 | 2015-10-27 | Facultes Universitaires Notre Dame De La Paix | Beta carboline derivatives useful in the treatment of proliferative disorders |
| JP5649170B2 (ja) * | 2010-11-26 | 2015-01-07 | 国立大学法人 千葉大学 | テトラヒドロ−β−カルボリン誘導体及びその製造方法 |
| CN103450199B (zh) * | 2012-06-01 | 2015-09-09 | 首都医科大学 | 茶氨酸修饰的咔啉酰氨基酸苄酯、其制备、抗肿瘤活性和应用 |
| WO2019028171A1 (en) | 2017-08-01 | 2019-02-07 | Ptc Therapeutics, Inc. | DHODH INHIBITOR FOR USE IN THE TREATMENT OF HEMATOLOGICAL CANCERS |
| US10947253B2 (en) | 2019-08-05 | 2021-03-16 | Ankh Life Sciences Limited | Fused polycyclic dimers |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES273769A1 (es) * | 1961-01-18 | 1962-06-01 | Geigy Ag J R | Procedimiento para la preparaciën de nuevos derivados de amidas de acido beta-carbolin-carboxilico |
| FR1310971A (fr) * | 1962-01-17 | 1962-11-30 | Geigy Ag J R | Nouveaux dérivés de la beta-carboline et leur préparation |
| FR1310970A (fr) * | 1962-01-17 | 1962-11-30 | Geigy Ag J R | Nouveaux dérivés de la beta-carboline à substituants basiques et leur préparation |
| US3644384A (en) * | 1969-06-09 | 1972-02-22 | Sterling Drug Inc | Certain 2-(alpha-haloacetyl) - 1 2 3 4-tetrahydro - 9h - pyrido(3 4-b)indole-3-carboxylates and derivatives |
| US4336260A (en) * | 1977-12-08 | 1982-06-22 | The Dow Chemical Company | Method and compositions using 1-aryl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid for treating depression |
| PH25651A (en) * | 1986-05-21 | 1991-08-21 | Duphar Int Res | New di, tetrahydroisoquinoline derivatives |
| EP0275307A1 (en) * | 1986-08-05 | 1988-07-27 | Harbor Branch Oceanographic Institution, Inc. | Antitumor compositions and their methods of use |
| ATE136032T1 (de) * | 1987-07-20 | 1996-04-15 | Duphar Int Res | 8,9-anellierte 1,2,3,4-tetrahydro-beta-carbolin- derivate |
| ZA889251B (en) * | 1987-12-14 | 1989-08-30 | Duphar Int Res | 8,9-annelated-beta-carbolines and 8,9-annelated-3,4-dihydro-beta-carbolines |
| EP0347980A1 (en) * | 1988-06-20 | 1989-12-27 | Duphar International Research B.V | 8,9-Annelated beta-carbolines and 8,9-anelated-3,4-dihydro-beta-carbolines |
| US4962163A (en) * | 1989-01-17 | 1990-10-09 | The Dow Chemical Company | Vinyl ester resins containing mesogenic/rigid rodlike moieties |
-
1989
- 1989-08-11 EP EP19890202089 patent/EP0357122A3/en not_active Ceased
- 1989-08-24 DK DK417289A patent/DK417289A/da unknown
- 1989-08-24 US US07/397,859 patent/US5095020A/en not_active Expired - Fee Related
- 1989-08-24 ZA ZA896473A patent/ZA896473B/xx unknown
- 1989-08-24 CA CA000609208A patent/CA1337200C/en not_active Expired - Fee Related
- 1989-08-25 NZ NZ230431A patent/NZ230431A/en unknown
- 1989-08-28 IL IL9145289A patent/IL91452A/en not_active IP Right Cessation
- 1989-08-28 AU AU40830/89A patent/AU625068B2/en not_active Ceased
- 1989-08-29 JP JP1220479A patent/JPH02111772A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| ZA896473B (en) | 1990-09-26 |
| US5095020A (en) | 1992-03-10 |
| EP0357122A3 (en) | 1991-10-23 |
| DK417289D0 (da) | 1989-08-24 |
| AU4083089A (en) | 1990-05-10 |
| AU625068B2 (en) | 1992-07-02 |
| NZ230431A (en) | 1992-03-26 |
| EP0357122A2 (en) | 1990-03-07 |
| CA1337200C (en) | 1995-10-03 |
| IL91452A0 (en) | 1990-04-29 |
| DK417289A (da) | 1990-03-01 |
| JPH02111772A (ja) | 1990-04-24 |
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Legal Events
| Date | Code | Title | Description |
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| RH | Patent void |