KR100886496B1 - 항종양성 엑티나시딘 유도체 - Google Patents
항종양성 엑티나시딘 유도체 Download PDFInfo
- Publication number
- KR100886496B1 KR100886496B1 KR1020027013749A KR20027013749A KR100886496B1 KR 100886496 B1 KR100886496 B1 KR 100886496B1 KR 1020027013749 A KR1020027013749 A KR 1020027013749A KR 20027013749 A KR20027013749 A KR 20027013749A KR 100886496 B1 KR100886496 B1 KR 100886496B1
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- group
- alkyl
- formula
- alkenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- ZHQQRIUYLMXDPP-ZETCQYMHSA-N actinidine Chemical class C1=NC=C(C)C2=C1[C@@H](C)CC2 ZHQQRIUYLMXDPP-ZETCQYMHSA-N 0.000 title abstract description 20
- 230000000259 anti-tumor effect Effects 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 243
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 12
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 9
- -1 cyano, hydroxyl Chemical group 0.000 claims description 129
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- 238000000034 method Methods 0.000 claims description 61
- 125000004432 carbon atom Chemical group C* 0.000 claims description 57
- 125000003118 aryl group Chemical group 0.000 claims description 46
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 125000003342 alkenyl group Chemical group 0.000 claims description 29
- 125000002252 acyl group Chemical group 0.000 claims description 26
- 229940079593 drug Drugs 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 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 claims description 16
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000004104 aryloxy group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000000468 ketone group Chemical group 0.000 claims description 11
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 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 claims description 8
- 229930012538 Paclitaxel Natural products 0.000 claims description 8
- 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 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 229960001592 paclitaxel Drugs 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 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 claims description 8
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 6
- 229960003957 dexamethasone Drugs 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- 229960002685 biotin Drugs 0.000 claims description 5
- 235000020958 biotin Nutrition 0.000 claims description 5
- 239000011616 biotin Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 4
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 229940009456 adriamycin Drugs 0.000 claims description 4
- 125000005518 carboxamido group Chemical group 0.000 claims description 4
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 4
- 229960004316 cisplatin Drugs 0.000 claims description 4
- 229960004397 cyclophosphamide Drugs 0.000 claims description 4
- 229960000684 cytarabine Drugs 0.000 claims description 4
- 229960003668 docetaxel Drugs 0.000 claims description 4
- 229960004679 doxorubicin Drugs 0.000 claims description 4
- 229960001904 epirubicin Drugs 0.000 claims description 4
- 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 claims description 4
- 229960005420 etoposide Drugs 0.000 claims description 4
- 229960002949 fluorouracil Drugs 0.000 claims description 4
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 4
- 229960005277 gemcitabine Drugs 0.000 claims description 4
- 229940022353 herceptin Drugs 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 4
- 229960001101 ifosfamide Drugs 0.000 claims description 4
- 229960000485 methotrexate Drugs 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 4
- 229960001756 oxaliplatin Drugs 0.000 claims description 4
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 claims description 4
- 229960002340 pentostatin Drugs 0.000 claims description 4
- UUSZLLQJYRSZIS-LXNNNBEUSA-N plitidepsin Chemical compound CN([C@H](CC(C)C)C(=O)N[C@@H]1C(=O)N[C@@H]([C@H](CC(=O)O[C@H](C(=O)[C@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N(C)[C@@H](CC=2C=CC(OC)=CC=2)C(=O)O[C@@H]1C)C(C)C)O)[C@@H](C)CC)C(=O)[C@@H]1CCCN1C(=O)C(C)=O UUSZLLQJYRSZIS-LXNNNBEUSA-N 0.000 claims description 4
- 229950008499 plitidepsin Drugs 0.000 claims description 4
- 108010049948 plitidepsin Proteins 0.000 claims description 4
- 229960001603 tamoxifen Drugs 0.000 claims description 4
- 229940063683 taxotere Drugs 0.000 claims description 4
- 229960003048 vinblastine Drugs 0.000 claims description 4
- 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 claims description 4
- 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 claims description 4
- 229960004528 vincristine Drugs 0.000 claims description 4
- 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 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
- 125000005251 aryl acyl group Chemical group 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims description 2
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims description 2
- 125000001288 lysyl group Chemical group 0.000 claims description 2
- 125000000405 phenylalanyl group Chemical group 0.000 claims description 2
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000002072 seryl group Chemical group 0.000 claims description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims 12
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims 10
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 claims 3
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims 3
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims 3
- 108010069236 Goserelin Proteins 0.000 claims 3
- 108010016076 Octreotide Proteins 0.000 claims 3
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 claims 3
- DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 claims 3
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 claims 3
- 229960002074 flutamide Drugs 0.000 claims 3
- 229960002913 goserelin Drugs 0.000 claims 3
- 229960002700 octreotide Drugs 0.000 claims 3
- 125000004641 (C1-C12) haloalkyl group Chemical group 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 125000005544 phthalimido group Chemical group 0.000 claims 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims 1
- 125000004643 (C1-C12) haloalkoxy group Chemical group 0.000 claims 1
- 125000001980 alanyl group Chemical group 0.000 claims 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229940126543 compound 14 Drugs 0.000 claims 1
- 125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 claims 1
- 125000001939 glutaminyl group Chemical group 0.000 claims 1
- 125000002073 methionyl group Chemical group 0.000 claims 1
- 150000003018 phosphorus compounds Chemical class 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 125000001239 threonyl group Chemical group 0.000 claims 1
- 125000002233 tyrosyl group Chemical group 0.000 claims 1
- ZHQQRIUYLMXDPP-SSDOTTSWSA-N Actinidine Natural products C1=NC=C(C)C2=C1[C@H](C)CC2 ZHQQRIUYLMXDPP-SSDOTTSWSA-N 0.000 abstract description 18
- 238000006243 chemical reaction Methods 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 34
- 239000000203 mixture Substances 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 29
- 238000003818 flash chromatography Methods 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000007858 starting material Substances 0.000 description 18
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 17
- 239000011734 sodium Substances 0.000 description 17
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical group O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 125000004122 cyclic group Chemical group 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 150000003462 sulfoxides Chemical class 0.000 description 15
- 0 C*[C@](C)(CNC)C(OC1CC1)=O Chemical compound C*[C@](C)(CNC)C(OC1CC1)=O 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 11
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- JNEGMBHBUAJRSX-SHUHUVMISA-N saframycin a Chemical compound C([C@H](N1C)[C@@H]2C#N)C(C(C(C)=C(OC)C3=O)=O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O JNEGMBHBUAJRSX-SHUHUVMISA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960002385 streptomycin sulfate Drugs 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000004964 sulfoalkyl group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 125000006488 t-butyl benzyl group Chemical group 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960000977 trabectedin Drugs 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- BYCZLYDXIYCSGW-UHFFFAOYSA-N tri(propan-2-yl)-(1h-pyrrol-2-yloxy)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)OC1=CC=CN1 BYCZLYDXIYCSGW-UHFFFAOYSA-N 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- 239000003744 tubulin modulator Substances 0.000 description 1
- 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 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D515/22—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 four or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0009043.1 | 2000-04-12 | ||
| GB0009043A GB0009043D0 (en) | 2000-04-12 | 2000-04-12 | New autitumoural derivatives of ET-743 |
| PCT/GB2000/001852 WO2000069862A2 (en) | 1999-05-14 | 2000-05-15 | Hemisynthetic method and intermediates thereof |
| GBPCT/GB00/01852 | 2000-05-15 | ||
| GB0022644A GB0022644D0 (en) | 2000-09-14 | 2000-09-14 | Antitumoral derivatives of ET-743 |
| GB0022644.9 | 2000-09-14 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20030012864A KR20030012864A (ko) | 2003-02-12 |
| KR100886496B1 true KR100886496B1 (ko) | 2009-03-05 |
Family
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| KR1020027013749A Expired - Lifetime KR100886496B1 (ko) | 2000-04-12 | 2001-04-12 | 항종양성 엑티나시딘 유도체 |
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| EP (1) | EP1280809B1 (enExample) |
| JP (1) | JP5219323B2 (enExample) |
| KR (1) | KR100886496B1 (enExample) |
| CN (1) | CN1436191B (enExample) |
| AR (1) | AR032879A1 (enExample) |
| AT (1) | ATE299146T1 (enExample) |
| AU (1) | AU784249C (enExample) |
| BG (1) | BG65987B1 (enExample) |
| BR (1) | BRPI0110024B8 (enExample) |
| CA (1) | CA2406080C (enExample) |
| CZ (1) | CZ304749B6 (enExample) |
| DE (1) | DE60111845T2 (enExample) |
| DK (1) | DK1280809T3 (enExample) |
| EA (1) | EA006206B1 (enExample) |
| ES (1) | ES2244598T3 (enExample) |
| HK (1) | HK1049005B (enExample) |
| HU (1) | HU230918B1 (enExample) |
| IL (1) | IL152094A (enExample) |
| MX (1) | MXPA02010088A (enExample) |
| NO (1) | NO329125B1 (enExample) |
| NZ (1) | NZ521550A (enExample) |
| PL (1) | PL210703B1 (enExample) |
| PT (1) | PT1280809E (enExample) |
| SI (1) | SI1280809T1 (enExample) |
| SK (1) | SK288017B6 (enExample) |
| WO (1) | WO2001077115A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1195514C (zh) | 1998-05-11 | 2005-04-06 | 法马马有限公司 | 海鞘素 743的代谢物 |
| MY164077A (en) | 1999-05-13 | 2017-11-30 | Pharma Mar Sa | Compositions and uses of et743 for treating cancer |
| MY130271A (en) | 1999-05-14 | 2007-06-29 | Pharma Mar Sa | Hemisynthetic method and new compounds |
| US7919493B2 (en) * | 2000-04-12 | 2011-04-05 | Pharma Mar, S.A. | Anititumoral ecteinascidin derivatives |
| US7420051B2 (en) | 2000-05-15 | 2008-09-02 | Pharma Mar, S.A. | Synthetic process for the manufacture of an ecteinaschidin compound |
| MXPA02011319A (es) | 2000-05-15 | 2003-06-06 | Pharma Mar Sa | Analogos antitumorales de ecteinascidina 743. |
| GB0117402D0 (en) * | 2001-07-17 | 2001-09-05 | Pharma Mar Sa | New antitumoral derivatives of et-743 |
| GB0119243D0 (en) * | 2001-08-07 | 2001-10-03 | Pharma Mar Sa | Antitumoral analogs of ET-743 |
| KR20050038578A (ko) * | 2001-10-19 | 2005-04-27 | 파르마 마르, 에스.에이. | 항종양성 화합물의 암치료에 있어서의 향상된 용도 |
| JP4208469B2 (ja) * | 2002-01-29 | 2009-01-14 | 独立行政法人科学技術振興機構 | エクテナサイジン類の全合成方法、エクテナサイジン類に類縁構造を持つ前記全合成用中間体化合物類、及び該中間体化合物類の合成方法 |
| GB0202544D0 (en) * | 2002-02-04 | 2002-03-20 | Pharma Mar Sa | The synthesis of naturally occuring ecteinascidins and related compounds |
| SI1689404T1 (sl) | 2003-11-13 | 2009-02-28 | Pharma Mar Sau | Kombinacija et-743 s 5-fluorouracil pro zdravili za zdravljenje raka |
| JP2008514688A (ja) * | 2004-09-29 | 2008-05-08 | ファルマ・マル・エス・アー， ソシエダッド・ユニペルソナル | 抗炎症剤としてのエクテイナシジン化合物 |
| RS50510B (sr) | 2004-10-29 | 2010-03-02 | Pharma Mar S.A., Sociedad Unipersonal | Formulacije koje sadrže ekteinascidin i disaharid |
| US8067462B2 (en) * | 2004-12-20 | 2011-11-29 | The Trustees Of Columbia University In The City Of New York | Processes of making sesquiterpenoid tashironin, its analogs and their uses |
| US20090131498A1 (en) * | 2005-01-18 | 2009-05-21 | Danishefsky Samuel J | Enantioselective Synthesis of Merrilactone and Its Analogs |
| GB0522082D0 (en) | 2005-10-31 | 2005-12-07 | Pharma Mar Sa | Formulations |
| WO2007087220A2 (en) * | 2006-01-25 | 2007-08-02 | The Trustees Of Columbia University In The City Of New York | The total synthesis of ecteinascidin 743 and derivatives thereof |
| FR2936951B1 (fr) * | 2008-10-10 | 2010-12-03 | Novexel | Nouvelles combinaisons de composes heterocycliques azotes antibacteriens avec d'autres composes antibacteriens et leur utilisation comme medicaments |
| CA2800097C (en) | 2010-05-25 | 2019-01-08 | Pharma Mar, S.A. | Synthetic process for the manufacture of ecteinascidin compounds and intermediates |
| KR102452022B1 (ko) | 2010-11-12 | 2022-10-06 | 파르마 마르 에스.에이. | 항종양 알칼로이드를 이용한 병용요법 |
| JOP20190254A1 (ar) * | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | مركبات مضادة للأورام |
| CN112679513B (zh) * | 2019-10-18 | 2023-08-25 | 南通诺泰生物医药技术有限公司 | 一种制备曲贝替定的关键中间体的方法 |
| PH12022551216A1 (en) | 2019-11-21 | 2023-07-17 | Pharma Mar Sa | Methods of treating small cell lung cancer with lurbinectedin formulations |
| CN114940682A (zh) * | 2022-05-18 | 2022-08-26 | 博瑞制药(苏州)有限公司 | 芦比替定的晶型及其制备方法和用途 |
| CN115677728A (zh) * | 2022-11-02 | 2023-02-03 | 成都科岭源医药技术有限公司 | 一种海鞘素类化合物中间体的制备方法 |
| IL322039A (en) * | 2023-01-17 | 2025-09-01 | Adcytherix Sas | The breads of ECTEINASCIDIN and antibodies |
| WO2025077996A1 (en) | 2023-10-09 | 2025-04-17 | Pharma Mar, S.A. | Synthetic process for the manufacture of ecteinascidin compounds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5721365A (en) * | 1989-09-15 | 1998-02-24 | Us Health | N-substituted piperazine NONOates |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59225189A (ja) | 1983-06-03 | 1984-12-18 | Shionogi & Co Ltd | キノナミン誘導体およびその製造法 |
| JPS6084288A (ja) | 1983-10-13 | 1985-05-13 | Shionogi & Co Ltd | シアノキノナミンアセテ−ト類およびその製造法 |
| US5089273A (en) | 1986-06-09 | 1992-02-18 | Board Of Trustees Of The University Of Illinois | Ecteinascidins 729, 743, 745, 759A, 759B and 770 |
| US5256663A (en) | 1986-06-09 | 1993-10-26 | The Board Of Trustees Of The University Of Illinois | Compositions comprising ecteinascidins and a method of treating herpes simplex virus infections therewith |
| EP0309477B1 (en) | 1986-06-09 | 1991-11-06 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins 729, 743, 745, 759a, 759b and 770 |
| US5149804A (en) | 1990-11-30 | 1992-09-22 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins 736 and 722 |
| US5478932A (en) | 1993-12-02 | 1995-12-26 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins |
| US5721362A (en) * | 1996-09-18 | 1998-02-24 | President And Fellows Of Harvard College | Process for producing ecteinascidin compounds |
| US5985876A (en) | 1997-04-15 | 1999-11-16 | Univ Illinois | Nucleophile substituted ecteinascidins and N-oxide ecteinascidins |
| CN1195514C (zh) | 1998-05-11 | 2005-04-06 | 法马马有限公司 | 海鞘素 743的代谢物 |
| US6124292A (en) | 1998-09-30 | 2000-09-26 | President And Fellows Of Harvard College | Synthetic analogs of ecteinascidin-743 |
| MY130271A (en) | 1999-05-14 | 2007-06-29 | Pharma Mar Sa | Hemisynthetic method and new compounds |
| EP1254140A4 (en) | 2000-01-19 | 2003-03-12 | Univ Columbia | SAFRAMYCIN-ECTEINASCIDIN SERIES COMPOUNDS, USES AND SYNTHESIS |
| MXPA02011319A (es) | 2000-05-15 | 2003-06-06 | Pharma Mar Sa | Analogos antitumorales de ecteinascidina 743. |
-
2001
- 2001-04-12 DE DE60111845T patent/DE60111845T2/de not_active Expired - Lifetime
- 2001-04-12 SK SK1435-2002A patent/SK288017B6/sk not_active IP Right Cessation
- 2001-04-12 BR BR0110024-6 patent/BRPI0110024B8/pt not_active IP Right Cessation
- 2001-04-12 CA CA2406080A patent/CA2406080C/en not_active Expired - Lifetime
- 2001-04-12 WO PCT/GB2001/001667 patent/WO2001077115A1/en not_active Ceased
- 2001-04-12 CN CN01810939XA patent/CN1436191B/zh not_active Expired - Lifetime
- 2001-04-12 KR KR1020027013749A patent/KR100886496B1/ko not_active Expired - Lifetime
- 2001-04-12 CZ CZ2002-3352A patent/CZ304749B6/cs not_active IP Right Cessation
- 2001-04-12 AT AT01919669T patent/ATE299146T1/de active
- 2001-04-12 HU HUP0300534A patent/HU230918B1/hu unknown
- 2001-04-12 PT PT01919669T patent/PT1280809E/pt unknown
- 2001-04-12 HK HK03101292.0A patent/HK1049005B/en not_active IP Right Cessation
- 2001-04-12 SI SI200130394T patent/SI1280809T1/sl unknown
- 2001-04-12 MX MXPA02010088A patent/MXPA02010088A/es active IP Right Grant
- 2001-04-12 IL IL152094A patent/IL152094A/en active IP Right Grant
- 2001-04-12 JP JP2001575588A patent/JP5219323B2/ja not_active Expired - Lifetime
- 2001-04-12 EP EP01919669A patent/EP1280809B1/en not_active Expired - Lifetime
- 2001-04-12 DK DK01919669T patent/DK1280809T3/da active
- 2001-04-12 NZ NZ521550A patent/NZ521550A/en not_active IP Right Cessation
- 2001-04-12 ES ES01919669T patent/ES2244598T3/es not_active Expired - Lifetime
- 2001-04-12 US US10/240,963 patent/US7202361B2/en not_active Expired - Lifetime
- 2001-04-12 PL PL357574A patent/PL210703B1/pl unknown
- 2001-04-12 EA EA200201083A patent/EA006206B1/ru not_active IP Right Cessation
- 2001-04-12 AU AU46729/01A patent/AU784249C/en not_active Expired
- 2001-04-16 AR ARP010101773A patent/AR032879A1/es active IP Right Grant
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2002
- 2002-10-11 NO NO20024906A patent/NO329125B1/no not_active IP Right Cessation
- 2002-10-24 BG BG107220A patent/BG65987B1/bg unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5721365A (en) * | 1989-09-15 | 1998-02-24 | Us Health | N-substituted piperazine NONOates |
Non-Patent Citations (1)
| Title |
|---|
| US 5721365 A.* |
Also Published As
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| KR100834601B1 (ko) | 반합성 방법 및 신규한 화합물 | |
| US7247629B2 (en) | Antitumoral analogs of et-743 | |
| US7919493B2 (en) | Anititumoral ecteinascidin derivatives | |
| KR100777464B1 (ko) | 엑티나시딘 화합물의 합성적인 제조 방법 | |
| JP4942900B2 (ja) | エクチナサイジン化合物の製造のための合成方法 |
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