CS265248B2 - Process for preparing analogs of rebeccamycine - Google Patents

Process for preparing analogs of rebeccamycine Download PDF

Info

Publication number: CS265248B2
Authority: CS; Czechoslovakia
Prior art keywords: rebeccamycin; formula; alkyl; derivative; hydrogen atom
Prior art date: 1986-11-21

Application number

CS878249A

Other languages

Czech (cs)

English (en)

Other versions

CS824987A2 (en

Inventor

Takushi Kaneko

Henry S Wong

Jacob J Utzig

Original Assignee

Bristol Myers Co

Priority date (The priority date 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 date listed.)

1986-11-21

Filing date

1987-11-17

Publication date

1989-10-13

1987-11-17 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1989-01-12 Publication of CS824987A2 publication Critical patent/CS824987A2/cs

1989-10-13 Publication of CS265248B2 publication Critical patent/CS265248B2/cs

Links

238000004519 manufacturing process Methods 0.000 title description 2
INSACQSBHKIWNS-QZQSLCQPSA-N rebeccamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](OC)[C@@H](CO)O[C@H]1N1C2=C3N=C4[C](Cl)C=CC=C4C3=C3C(=O)NC(=O)C3=C2C2=CC=CC(Cl)=C21 INSACQSBHKIWNS-QZQSLCQPSA-N 0.000 claims abstract description 34
150000001875 compounds Chemical class 0.000 claims abstract description 30
ZGCSNRKSJLVANE-UHFFFAOYSA-N Aglycone-Rebeccamycin Natural products N1C2=C3NC4=C(Cl)C=CC=C4C3=C(C(=O)NC3=O)C3=C2C2=C1C(Cl)=CC=C2 ZGCSNRKSJLVANE-UHFFFAOYSA-N 0.000 claims abstract description 27
QEHOIJJIZXRMAN-UHFFFAOYSA-N Rebeccamycin Natural products OC1C(O)C(OC)C(CO)OC1N1C2=C3NC4=C(Cl)C=CC=C4C3=C3C(=O)NC(=O)C3=C2C2=CC=CC(Cl)=C21 QEHOIJJIZXRMAN-UHFFFAOYSA-N 0.000 claims abstract description 27
229960005567 rebeccamycin Drugs 0.000 claims abstract description 27
-1 nitro, carboxyl Chemical group 0.000 claims abstract description 18
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 11
150000003839 salts Chemical class 0.000 claims abstract description 9
239000002253 acid Substances 0.000 claims abstract description 8
125000000217 alkyl group Chemical group 0.000 claims abstract description 7
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
239000001257 hydrogen Substances 0.000 claims abstract description 6
239000012048 reactive intermediate Substances 0.000 claims abstract description 6
229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
239000007858 starting material Substances 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 13
125000004103 aminoalkyl group Chemical group 0.000 claims description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
238000000034 method Methods 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
150000001450 anions Chemical class 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
239000012442 inert solvent Substances 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
JSKFWUPVIZYJMR-UHFFFAOYSA-N 1,11-dichloro-6-[2-(diethylamino)ethyl]-12-(4-o-methylhexopyranosyl)-12,13-dihydro-5h-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6h)-dione Chemical class O=C1N(CCN(CC)CC)C(=O)C(C2=C3[CH]C=CC(Cl)=C3NC2=C23)=C1C2=C1C=CC=C(Cl)[C]1N3C1OC(CO)C(OC)C(O)C1O JSKFWUPVIZYJMR-UHFFFAOYSA-N 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
239000011541 reaction mixture Substances 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
239000012298 atmosphere Substances 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
150000003254 radicals Chemical class 0.000 claims 2
238000010171 animal model Methods 0.000 abstract description 6
239000002246 antineoplastic agent Substances 0.000 abstract description 5
230000000118 anti-neoplastic effect Effects 0.000 abstract description 3
125000004433 nitrogen atom Chemical group N* 0.000 abstract description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 2
206010028980 Neoplasm Diseases 0.000 abstract description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 4
125000003545 alkoxy group Chemical group 0.000 abstract 3
125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 3
125000003118 aryl group Chemical group 0.000 abstract 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 2
125000004663 dialkyl amino group Chemical group 0.000 abstract 2
125000001475 halogen functional group Chemical group 0.000 abstract 2
125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 2
125000003710 aryl alkyl group Chemical group 0.000 abstract 1
125000004093 cyano group Chemical group *C#N 0.000 abstract 1
239000000203 mixture Substances 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
125000004122 cyclic group Chemical group 0.000 description 7
239000007788 liquid Substances 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
239000000969 carrier Substances 0.000 description 6
239000007787 solid Substances 0.000 description 5
230000004614 tumor growth Effects 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
241000970318 Lechevalieria aerocolonigenes Species 0.000 description 4
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
239000002904 solvent Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
WVUULNDRFBHTFG-UHFFFAOYSA-N 3-chloro-n,n-diethylpropan-1-amine Chemical compound CCN(CC)CCCCl WVUULNDRFBHTFG-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
201000011510 cancer Diseases 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
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000001819 mass spectrum Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
239000007818 Grignard reagent Substances 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
229930187135 Olivomycin Natural products 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000000872 buffer Substances 0.000 description 2
238000012258 culturing Methods 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000003480 eluent Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
208000032839 leukemia Diseases 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
229960004857 mitomycin Drugs 0.000 description 2
CZDBNBLGZNWKMC-MWQNXGTOSA-N olivomycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1)O[C@H]1O[C@@H](C)[C@H](O)[C@@H](OC2O[C@@H](C)[C@H](O)[C@@H](O)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@H](O)[C@H](OC)[C@H](C)O1 CZDBNBLGZNWKMC-MWQNXGTOSA-N 0.000 description 2
229950005848 olivomycin Drugs 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
229910001923 silver oxide Inorganic materials 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
239000004375 Dextrin Substances 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
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
229930182474 N-glycoside Natural products 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-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
239000004480 active ingredient Substances 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
229940034982 antineoplastic agent Drugs 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
239000012059 conventional drug carrier Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
238000010586 diagram Methods 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000008393 encapsulating agent Substances 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000029142 excretion Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000005858 glycosidation reaction Methods 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
230000012010 growth Effects 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
150000002475 indoles Chemical class 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
239000008101 lactose Substances 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
229960003646 lysine Drugs 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 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
239000000463 material Substances 0.000 description 1
231100000682 maximum tolerated dose Toxicity 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000010992 reflux Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000008215 water for injection Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/044—Pyrrole radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/23—Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Compounds Of Unknown Constitution (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines Containing Plant Substances (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CS878249A 1986-11-21 1987-11-17 Process for preparing analogs of rebeccamycine CS265248B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US06/933,428 US4785085A (en)	1986-11-21	1986-11-21	Rebeccamycin analogs

Publications (2)

Publication Number	Publication Date
CS824987A2 CS824987A2 (en)	1989-01-12
CS265248B2 true CS265248B2 (en)	1989-10-13

Family

ID=25463937

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS878249A CS265248B2 (en)	1986-11-21	1987-11-17	Process for preparing analogs of rebeccamycine

Country Status (28)

Country	Link
US (1)	US4785085A (no)
EP (1)	EP0269025B1 (no)
JP (1)	JPS63198695A (no)
KR (1)	KR910000897B1 (no)
CN (1)	CN1019806B (no)
AT (1)	ATE84539T1 (no)
AU (1)	AU614068B2 (no)
CA (1)	CA1287349C (no)
CS (1)	CS265248B2 (no)
CY (1)	CY1701A (no)
DE (1)	DE3783577T2 (no)
DK (1)	DK165986C (no)
EG (1)	EG18409A (no)
ES (1)	ES2053510T3 (no)
FI (1)	FI86189C (no)
GR (1)	GR3006776T3 (no)
HK (1)	HK49093A (no)
HU (1)	HU201773B (no)
IE (1)	IE60595B1 (no)
IL (1)	IL84515A (no)
MX (1)	MX9202849A (no)
MY (1)	MY102722A (no)
NO (1)	NO167741C (no)
NZ (1)	NZ222544A (no)
PT (1)	PT86188B (no)
SG (1)	SG25193G (no)
YU (1)	YU46087B (no)
ZA (1)	ZA878714B (no)

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US5344823A (en) *	1990-03-06	1994-09-06	Bristol-Myers Squibb Company	Antitumor antibiotic BMY-41219
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NZ245203A (en) *	1991-11-29	1997-07-27	Banyu Pharma Co Ltd	5h-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6h)-dione derivatives substituted in position-13 by a pentose or hexose group; corresponding indolo-furano(anhydride)intermediates
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JPH07504674A (ja) *	1992-03-20	1995-05-25	ザ・ウエルカム・ファウンデーション・リミテッド	抗ウイルス活性を有する更なるインドール誘導体
JP3603322B2 (ja) *	1992-12-14	2004-12-22	萬有製薬株式会社	インドロピロロカルバゾール誘導体の製造法
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US5624949A (en) *	1993-12-07	1997-04-29	Eli Lilly And Company	Protein kinase C inhibitors
US5541347A (en) *	1993-12-07	1996-07-30	Eli Lilly And Company	Synthesis of bisindolylmaleimides
HUT69164A (en) *	1993-12-07	1995-08-28	Lilly Co Eli	Improved process for producing bis-indolyl-maleimide derivatives
US5723456A (en) *	1993-12-07	1998-03-03	Eli Lilly & Company	Therapeutic treatment for cardiovascular diseases
ES2162843T3 (es) *	1993-12-07	2002-01-16	Lilly Co Eli	Inhibidores de la proteina quinasa c.
DK0817627T3 (da) *	1993-12-23	2005-06-06	Lilly Co Eli	Inhibitorer af proteinkinase C
US5545636A (en) *	1993-12-23	1996-08-13	Eli Lilly And Company	Protein kinase C inhibitors
WO1995030682A1 (fr) *	1994-05-09	1995-11-16	Banyu Pharmaceutical Co., Ltd.	Derive d'indolopyrolocarbazole antitumoral
US5922860A (en) *	1994-05-09	1999-07-13	Banyu Pharmaceutical Co., Ltd.	Antitumor indolopyrrolocarbazole derivatives
US5804564A (en) *	1994-05-09	1998-09-08	Banyu Pharmaceutical Co., Ltd.	Antitumor indolopyrrolocarbazole derivatives
US5861293A (en) *	1994-06-13	1999-01-19	Banyu Pharmaceutical Co., Ltd.	Gene encoding glycosyltransferase and its uses
US5481003A (en) *	1994-06-22	1996-01-02	Eli Lilly And Company	Protein kinase C inhibitors
US5491242A (en) *	1994-06-22	1996-02-13	Eli Lilly And Company	Protein kinase C inhibitors
EP0695755B1 (en) *	1994-08-04	1998-10-21	F. Hoffmann-La Roche AG	Pyrrolocarbazole
AU6836696A (en) *	1995-09-05	1997-03-27	Banyu Pharmaceutical Co., Ltd.	Antitumor indolopyrrolocarbazole derivatives
IL126272A0 (en) *	1996-03-20	1999-05-09	Lilly Co Eli	Synthesis of indolylmaleimides
US5859261A (en) *	1997-03-20	1999-01-12	Eli Lilly And Company	Synthesis of indolylmaleimides
US6677450B2 (en)	2000-10-06	2004-01-13	Bristol-Myers Squibb Company	Topoisomerase inhibitors
US6653290B2 (en)	2000-10-06	2003-11-25	Bristol-Myers Squibb Company	Tumor proliferation inhibitors
US6610727B2 (en)	2000-10-06	2003-08-26	Bristol-Myers Squibb Company	Anhydro sugar derivatives of indolocarbazoles
BR0208322A (pt)	2001-03-22	2004-10-13	Bristol Myers Squibb Co	Derivados de açúcar citotóxixo seletivo da topoisomerase i de indolopirrolocarbazóis
AU2002322720B2 (en)	2001-07-25	2008-11-13	Raptor Pharmaceutical Inc.	Compositions and methods for modulating blood-brain barrier transport
CA2393720C (en) *	2002-07-12	2010-09-14	Eli Lilly And Company	Crystalline 2,5-dione-3-(1-methyl-1h-indol-3-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1h-indol-3-yl]-1h-pyrrole mono-hydrochloride
AU2004272457A1 (en) *	2003-09-16	2005-03-24	Banyu Pharmaceutical Co., Ltd.	Novel indolopyrrolocarbazole derivative with antitumor activity
CN103259027A (zh)	2005-04-28	2013-08-21	普罗透斯数字保健公司	药物信息系统
EP2063905B1 (en)	2006-09-18	2014-07-30	Raptor Pharmaceutical Inc	Treatment of liver disorders by administration of receptor-associated protein (rap)-conjugates
ES2326459B1 (es)	2008-04-08	2010-05-28	Universidad De Oviedo	Indolocarbazoles glicosilados, su procedimiento de obtencion y sus usos.
CN102316902B (zh)	2009-02-20	2014-09-24	to-BBB控股股份有限公司	基于谷胱甘肽的药物递送系统
CN110075069A (zh)	2009-05-06	2019-08-02	实验室护肤股份有限公司	包含活性剂-磷酸钙颗粒复合物的皮肤递送组合物及其应用
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US4524145A (en) *	1984-09-04	1985-06-18	Bristol-Myers Company	4'-Deschlororebeccamycin pharmaceutical composition and method of use
JPS62220196A (ja) *	1986-03-20	1987-09-28	Kyowa Hakko Kogyo Co Ltd	新規物質ｕｃｎ―０１

1986
- 1986-11-21 US US06/933,428 patent/US4785085A/en not_active Expired - Lifetime
1987
- 1987-11-12 AU AU81148/87A patent/AU614068B2/en not_active Expired
- 1987-11-13 NZ NZ222544A patent/NZ222544A/en unknown
- 1987-11-17 EG EG656/87A patent/EG18409A/xx active
- 1987-11-17 CS CS878249A patent/CS265248B2/cs not_active IP Right Cessation
- 1987-11-18 YU YU208687A patent/YU46087B/sh unknown
- 1987-11-18 IL IL84515A patent/IL84515A/xx not_active IP Right Cessation
- 1987-11-18 FI FI875091A patent/FI86189C/fi not_active IP Right Cessation
- 1987-11-20 DE DE8787117167T patent/DE3783577T2/de not_active Expired - Lifetime
- 1987-11-20 PT PT86188A patent/PT86188B/pt unknown
- 1987-11-20 JP JP62293854A patent/JPS63198695A/ja active Granted
- 1987-11-20 IE IE315287A patent/IE60595B1/en not_active IP Right Cessation
- 1987-11-20 HU HU875164A patent/HU201773B/hu unknown
- 1987-11-20 NO NO874857A patent/NO167741C/no not_active IP Right Cessation
- 1987-11-20 CN CN87107928A patent/CN1019806B/zh not_active Expired
- 1987-11-20 KR KR1019870013102A patent/KR910000897B1/ko not_active IP Right Cessation
- 1987-11-20 AT AT87117167T patent/ATE84539T1/de not_active IP Right Cessation
- 1987-11-20 ZA ZA878714A patent/ZA878714B/xx unknown
- 1987-11-20 DK DK612987A patent/DK165986C/da not_active IP Right Cessation
- 1987-11-20 ES ES87117167T patent/ES2053510T3/es not_active Expired - Lifetime
- 1987-11-20 EP EP87117167A patent/EP0269025B1/en not_active Expired - Lifetime
- 1987-11-20 CA CA000552337A patent/CA1287349C/en not_active Expired - Lifetime
- 1987-11-20 MY MYPI87003080A patent/MY102722A/en unknown
1992
- 1992-06-12 MX MX9202849A patent/MX9202849A/es unknown
1993
- 1993-01-14 GR GR920402547T patent/GR3006776T3/el unknown
- 1993-03-06 SG SG251/93A patent/SG25193G/en unknown
- 1993-05-20 HK HK490/93A patent/HK49093A/xx not_active IP Right Cessation
1994
- 1994-01-14 CY CY170194A patent/CY1701A/xx unknown

Also Published As

Publication number	Publication date
PT86188B (pt)	1990-11-07
ZA878714B (no)	1988-05-20
HUT45543A (en)	1988-07-28
HU201773B (en)	1990-12-28
NO167741C (no)	1991-12-04
DK612987A (da)	1988-05-22
PT86188A (en)	1987-12-01
GR3006776T3 (no)	1993-06-30
ES2053510T3 (es)	1994-08-01
IL84515A0 (en)	1988-04-29
MX9202849A (es)	1992-06-30
EP0269025B1 (en)	1993-01-13
IE873152L (en)	1988-05-21
HK49093A (en)	1993-05-27
KR910000897B1 (ko)	1991-02-12
EP0269025A2 (en)	1988-06-01
CA1287349C (en)	1991-08-06
CN1019806B (zh)	1992-12-30
KR880006246A (ko)	1988-07-22
CY1701A (en)	1994-01-14
JPS63198695A (ja)	1988-08-17
MY102722A (en)	1992-09-30
IE60595B1 (en)	1994-07-27
SG25193G (en)	1993-05-21
FI86189C (fi)	1992-07-27
DE3783577D1 (de)	1993-02-25
DK165986C (da)	1993-07-19
YU46087B (sh)	1992-12-21
CS824987A2 (en)	1989-01-12
DK612987D0 (da)	1987-11-20
ATE84539T1 (de)	1993-01-15
US4785085A (en)	1988-11-15
NO874857L (no)	1988-05-24
IL84515A (en)	1991-11-21
YU208687A (en)	1988-10-31
DK165986B (da)	1993-02-22
JPH05400B2 (no)	1993-01-05
NO874857D0 (no)	1987-11-20
FI875091A0 (fi)	1987-11-18
DE3783577T2 (de)	1993-05-19
EG18409A (en)	1993-02-28
NZ222544A (en)	1990-11-27
EP0269025A3 (en)	1990-08-29
FI86189B (fi)	1992-04-15
AU8114887A (en)	1988-05-26
NO167741B (no)	1991-08-26
CN87107928A (zh)	1988-08-10
FI875091A (fi)	1988-05-22
AU614068B2 (en)	1991-08-22

Publication	Publication Date	Title
CS265248B2 (en)	1989-10-13	Process for preparing analogs of rebeccamycine
US5070092A (en)	1991-12-03	Pyrroloindole derivatives related to dc-88a compound
US5187186A (en)	1993-02-16	Pyrroloindole derivatives
US4808613A (en)	1989-02-28	Rebeccamycin derivative containing pharmaceutical composition
EP0823429B1 (en)	2000-07-12	Radicicol derivatives
EP0580812A1 (en)	1994-02-02	Anti-tumor and anti-psoriatic agents
HU219232B (en)	2001-03-28	Bis-naphthalimide derivatives, process for producing them, and pharmaceutical compositions containing them
FR2801054A1 (fr)	2001-05-18	Nouveaux derives de 12,13-(pyranosyl)-indolo[2,3-a]pyrrolo [3,4-c]carbazole et 12,13-(pyranosyl)-furo[3,4-c]indolo [2,3-a]carbazole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
HU217551B (hu)	2000-02-28	6[(2-Hidroxi-etil)-amino-alkil]-5,11-dioxo-5,6-dihidro-11H-indén[1,2-c]izokinolin-származékok, valamint eljárás előállításukra, továbbá hatóanyagként e vegyületeket tartalmazó gyógyászati készítmények
FR2845996A1 (fr)	2004-04-23	Nouveaux derives de[3,4-a:3,4-c]carbazole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
JP2001526290A (ja)	2001-12-18	新規アクロニシン化合物、その製造方法及びそれを含有する医薬組成物
US4460599A (en)	1984-07-17	Mitomycin analogs
EP0378706B1 (en)	1994-12-28	5-substituted uridine derivatives and intermediates for their preparation
US4576945A (en)	1986-03-18	Hexaalkylmelamine-amino-oxy compounds
US5100881A (en)	1992-03-31	N-(23-vincristinoyl) and n-(5'-noranhydro-23-vinblastinoyl) compounds of 1-aminomethylphosphonic acid useful for the treatment of neoplastic diseases
US5218126A (en)	1993-06-08	Halogen substituted mitomycin derivatives
US5097036A (en)	1992-03-17	Substituted 7-oxomitosanes
US5099016A (en)	1992-03-24	Substituted 7-oxomitosanes
JPH0834788A (ja)	1996-02-06	ピロロベンゾカルバゾール誘導体及びその製造方法
EP0456514B1 (en)	1994-10-19	2-Fluoroneplanocin A and its production
EP0601520A1 (en)	1994-06-15	Trifluorothymidine derivatives, process for producing the same and anti-cancer agent containing the same
JPH0834789A (ja)	1996-02-06	ピロロインドールカルボン酸エステル誘導体及びその製造方法
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JPH0834786A (ja)	1996-02-06	トリフルオロメチルピロロインドール誘導体及びその製造方法
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