UA77400C2 - Variolin b derivatives, pharmaceutical composition, method for production, intermadiates - Google Patents
Variolin b derivatives, pharmaceutical composition, method for production, intermadiates Download PDFInfo
- Publication number
- UA77400C2 UA77400C2 UA2003021828A UA2003021828A UA77400C2 UA 77400 C2 UA77400 C2 UA 77400C2 UA 2003021828 A UA2003021828 A UA 2003021828A UA 2003021828 A UA2003021828 A UA 2003021828A UA 77400 C2 UA77400 C2 UA 77400C2
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- UA
- Ukraine
- Prior art keywords
- group
- pyrrolo
- compound according
- solution
- mixture
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 229930186114 Variolin Natural products 0.000 title description 4
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 125000001424 substituent group Chemical group 0.000 claims abstract description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 31
- -1 4-pyrimidyl group Chemical group 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 125000003277 amino group Chemical group 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 230000003993 interaction Effects 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 150000001491 aromatic compounds Chemical class 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 238000001212 derivatisation Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 125000006413 ring segment Chemical group 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 4
- 230000000259 anti-tumor effect Effects 0.000 abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 2
- 239000000243 solution Substances 0.000 description 114
- 239000000203 mixture Substances 0.000 description 101
- 125000004432 carbon atom Chemical group C* 0.000 description 52
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- 238000005481 NMR spectroscopy Methods 0.000 description 48
- 239000007787 solid Substances 0.000 description 44
- 238000005160 1H NMR spectroscopy Methods 0.000 description 34
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 30
- 238000010828 elution Methods 0.000 description 23
- 238000003818 flash chromatography Methods 0.000 description 23
- 239000002904 solvent Substances 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 101100229939 Mus musculus Gpsm1 gene Proteins 0.000 description 16
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 16
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 14
- RTHKPHCVZVYDFN-UHFFFAOYSA-N 9-amino-5-(2-aminopyrimidin-4-yl)pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidin-4-ol Chemical class NC1=NC=CC(C=2C3=C(O)C=CN=C3N3C(N)=NC=CC3=2)=N1 RTHKPHCVZVYDFN-UHFFFAOYSA-N 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- JTQQDEMYPLKSDW-UHFFFAOYSA-N 5-(2-aminopyrimidin-4-yl)pyrido[2,3]pyrrolo[4,5-c]pyrimidin-9-amine Chemical class NC1=NC=CC(C2=C3C=CN=C(N)N3C3=NC=CC=C32)=N1 JTQQDEMYPLKSDW-UHFFFAOYSA-N 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- LMRDBJZQDUVCQH-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)acetaldehyde Chemical compound C1=CC=C2C(=O)N(CC=O)C(=O)C2=C1 LMRDBJZQDUVCQH-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- 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
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 238000006138 lithiation reaction Methods 0.000 description 4
- YPOZZIHTGQNUOW-UHFFFAOYSA-N n-(4-chloropyrimidin-2-yl)acetamide Chemical compound CC(=O)NC1=NC=CC(Cl)=N1 YPOZZIHTGQNUOW-UHFFFAOYSA-N 0.000 description 4
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- RCFQIMPQKOTUCJ-UHFFFAOYSA-N trimethyl(pyrimidin-2-yl)stannane Chemical class C[Sn](C)(C)C1=NC=CC=N1 RCFQIMPQKOTUCJ-UHFFFAOYSA-N 0.000 description 4
- UZSRWAXAZAAPKC-UHFFFAOYSA-N 2-[2-hydroxy-2-(1h-pyrrolo[2,3-b]pyridin-2-yl)ethyl]isoindole-1,3-dione Chemical compound C1=CN=C2NC(C(CN3C(C4=CC=CC=C4C3=O)=O)O)=CC2=C1 UZSRWAXAZAAPKC-UHFFFAOYSA-N 0.000 description 3
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
- BWVZLXTZQHILRC-UHFFFAOYSA-N 4-chloro-2-methylsulfonylpyrimidine Chemical compound CS(=O)(=O)C1=NC=CC(Cl)=N1 BWVZLXTZQHILRC-UHFFFAOYSA-N 0.000 description 3
- DBGFGNCFYUNXLD-UHFFFAOYSA-N 4-chloropyrimidin-2-amine Chemical compound NC1=NC=CC(Cl)=N1 DBGFGNCFYUNXLD-UHFFFAOYSA-N 0.000 description 3
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
- 125000002015 acyclic group Chemical group 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- GQFDUSIKHMUDSF-UHFFFAOYSA-N n-(4-trimethylstannylpyrimidin-2-yl)acetamide Chemical compound CC(=O)NC1=NC=CC([Sn](C)(C)C)=N1 GQFDUSIKHMUDSF-UHFFFAOYSA-N 0.000 description 3
- QQABYHBSEHZESN-UHFFFAOYSA-N n-acetyl-n-(4-chloropyrimidin-2-yl)acetamide Chemical compound CC(=O)N(C(C)=O)C1=NC=CC(Cl)=N1 QQABYHBSEHZESN-UHFFFAOYSA-N 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 125000004001 thioalkyl group Chemical group 0.000 description 3
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- ZYRVRQJQZZWLSI-UHFFFAOYSA-N 2-(4-methoxy-1h-pyrrolo[2,3-b]pyridin-2-yl)-2-(oxan-2-yloxy)ethanamine Chemical compound C=1C=2C(OC)=CC=NC=2NC=1C(CN)OC1CCCCO1 ZYRVRQJQZZWLSI-UHFFFAOYSA-N 0.000 description 2
- JLIDXOMKNOMYBB-UHFFFAOYSA-N 2-[2-hydroxy-2-(4-methoxy-1h-pyrrolo[2,3-b]pyridin-2-yl)ethyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC(O)C(N1)=CC2=C1N=CC=C2OC JLIDXOMKNOMYBB-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin 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-VTZDEGQISA-N 0.000 description 2
- DNIKOOPKCLWWPO-UHFFFAOYSA-N 4-methoxy-1h-pyrrolo[2,3-b]pyridine Chemical compound COC1=CC=NC2=C1C=CN2 DNIKOOPKCLWWPO-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 102100029645 UBX domain-containing protein 11 Human genes 0.000 description 2
- BBEBAMDMYAUOLG-UHFFFAOYSA-N Variolin A Natural products N=C1N(C)C=C(O)C(C=2C=3C(=O)C=CNC=3N3C(N)=NC=CC3=2)=N1 BBEBAMDMYAUOLG-UHFFFAOYSA-N 0.000 description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000005236 alkanoylamino group Chemical group 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960001904 epirubicin Drugs 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
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- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
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- 229960001592 paclitaxel Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000003744 tubulin modulator Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 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
- C07D471/12—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Compounds Of Unknown Constitution (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0019117.1A GB0019117D0 (en) | 2000-08-03 | 2000-08-03 | Derivatives of variolin B |
| PCT/GB2001/003517 WO2002012240A1 (fr) | 2000-08-03 | 2001-08-03 | Dérivés de varioline b |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA77400C2 true UA77400C2 (en) | 2006-12-15 |
Family
ID=9896947
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2003021828A UA77400C2 (en) | 2000-08-03 | 2001-03-08 | Variolin b derivatives, pharmaceutical composition, method for production, intermadiates |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US7329666B2 (fr) |
| EP (1) | EP1307454B1 (fr) |
| JP (1) | JP2004505976A (fr) |
| KR (1) | KR100937606B1 (fr) |
| CN (1) | CN1275965C (fr) |
| AT (1) | ATE432932T1 (fr) |
| AU (2) | AU7651001A (fr) |
| BR (1) | BR0112920A (fr) |
| CA (1) | CA2417629C (fr) |
| CY (1) | CY1109337T1 (fr) |
| DE (1) | DE60138889D1 (fr) |
| DK (1) | DK1307454T3 (fr) |
| ES (1) | ES2328013T3 (fr) |
| GB (1) | GB0019117D0 (fr) |
| IL (2) | IL154155A0 (fr) |
| MX (1) | MXPA03001047A (fr) |
| NZ (1) | NZ523864A (fr) |
| PT (1) | PT1307454E (fr) |
| RU (1) | RU2293737C2 (fr) |
| SI (1) | SI1307454T1 (fr) |
| UA (1) | UA77400C2 (fr) |
| WO (1) | WO2002012240A1 (fr) |
| ZA (1) | ZA200300797B (fr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2799757B1 (fr) * | 1999-10-15 | 2001-12-14 | Adir | Nouveaux derives polycycliques azaindoliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| AU2001270783B2 (en) * | 2000-07-11 | 2006-06-15 | Pharma Mar, S.A. | Variolin derivatives as anti-cancer agents |
| GB0116966D0 (en) | 2001-07-11 | 2001-09-05 | Pharma Mar Sa | Anittumoral compounds |
| EP2313102A2 (fr) | 2008-07-03 | 2011-04-27 | Biota Scientific Management | Nucléosides bicycliques et nucléotides convenant comme agents thérapeutiques |
| CN106674132B (zh) * | 2016-11-22 | 2019-04-26 | 上海书亚医药科技有限公司 | 一种嘧啶类除草剂的制备方法与应用 |
| US11332480B2 (en) | 2017-04-27 | 2022-05-17 | Pharma Mar, S.A. | Antitumoral compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001270783B2 (en) * | 2000-07-11 | 2006-06-15 | Pharma Mar, S.A. | Variolin derivatives as anti-cancer agents |
| GB0116966D0 (en) * | 2001-07-11 | 2001-09-05 | Pharma Mar Sa | Anittumoral compounds |
-
2000
- 2000-08-03 GB GBGB0019117.1A patent/GB0019117D0/en not_active Ceased
-
2001
- 2001-03-08 UA UA2003021828A patent/UA77400C2/uk unknown
- 2001-08-03 ES ES01954163T patent/ES2328013T3/es not_active Expired - Lifetime
- 2001-08-03 US US10/343,391 patent/US7329666B2/en not_active Expired - Fee Related
- 2001-08-03 CN CNB018166652A patent/CN1275965C/zh not_active Expired - Fee Related
- 2001-08-03 EP EP01954163A patent/EP1307454B1/fr not_active Expired - Lifetime
- 2001-08-03 BR BR0112920-1A patent/BR0112920A/pt not_active IP Right Cessation
- 2001-08-03 NZ NZ523864A patent/NZ523864A/en unknown
- 2001-08-03 DK DK01954163T patent/DK1307454T3/da active
- 2001-08-03 SI SI200130929T patent/SI1307454T1/sl unknown
- 2001-08-03 WO PCT/GB2001/003517 patent/WO2002012240A1/fr not_active Ceased
- 2001-08-03 MX MXPA03001047A patent/MXPA03001047A/es active IP Right Grant
- 2001-08-03 CA CA2417629A patent/CA2417629C/fr not_active Expired - Fee Related
- 2001-08-03 AU AU7651001A patent/AU7651001A/xx active Pending
- 2001-08-03 DE DE60138889T patent/DE60138889D1/de not_active Expired - Lifetime
- 2001-08-03 KR KR1020037001574A patent/KR100937606B1/ko not_active Expired - Fee Related
- 2001-08-03 AU AU2001276510A patent/AU2001276510B2/en not_active Ceased
- 2001-08-03 RU RU2003105824/04A patent/RU2293737C2/ru not_active IP Right Cessation
- 2001-08-03 JP JP2002518215A patent/JP2004505976A/ja active Pending
- 2001-08-03 PT PT01954163T patent/PT1307454E/pt unknown
- 2001-08-03 IL IL15415501A patent/IL154155A0/xx unknown
- 2001-08-03 AT AT01954163T patent/ATE432932T1/de active
-
2003
- 2003-01-27 IL IL154155A patent/IL154155A/en not_active IP Right Cessation
- 2003-01-29 ZA ZA200300797A patent/ZA200300797B/en unknown
-
2007
- 2007-07-27 US US11/829,379 patent/US20080033001A1/en not_active Abandoned
-
2009
- 2009-09-01 CY CY20091100914T patent/CY1109337T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200300797B (en) | 2004-04-29 |
| MXPA03001047A (es) | 2004-02-26 |
| US20080033001A1 (en) | 2008-02-07 |
| ES2328013T3 (es) | 2009-11-06 |
| IL154155A (en) | 2010-05-31 |
| KR20030038684A (ko) | 2003-05-16 |
| RU2293737C2 (ru) | 2007-02-20 |
| US20040058939A1 (en) | 2004-03-25 |
| BR0112920A (pt) | 2003-07-01 |
| DE60138889D1 (de) | 2009-07-16 |
| JP2004505976A (ja) | 2004-02-26 |
| IL154155A0 (en) | 2003-07-31 |
| NZ523864A (en) | 2004-09-24 |
| CA2417629C (fr) | 2010-10-19 |
| DK1307454T3 (da) | 2009-09-14 |
| CN1275965C (zh) | 2006-09-20 |
| ATE432932T1 (de) | 2009-06-15 |
| SI1307454T1 (sl) | 2009-12-31 |
| CA2417629A1 (fr) | 2002-02-14 |
| AU2001276510B2 (en) | 2007-01-25 |
| US7329666B2 (en) | 2008-02-12 |
| GB0019117D0 (en) | 2000-09-27 |
| EP1307454B1 (fr) | 2009-06-03 |
| AU7651001A (en) | 2002-02-18 |
| PT1307454E (pt) | 2009-09-03 |
| CY1109337T1 (el) | 2014-07-02 |
| EP1307454A1 (fr) | 2003-05-07 |
| KR100937606B1 (ko) | 2010-01-20 |
| WO2002012240A1 (fr) | 2002-02-14 |
| CN1468240A (zh) | 2004-01-14 |
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