NL8403852A - Acylamino mitosanen; werkwijze voor het bereiden daarvan. - Google Patents
Acylamino mitosanen; werkwijze voor het bereiden daarvan. Download PDFInfo
- Publication number
- NL8403852A NL8403852A NL8403852A NL8403852A NL8403852A NL 8403852 A NL8403852 A NL 8403852A NL 8403852 A NL8403852 A NL 8403852A NL 8403852 A NL8403852 A NL 8403852A NL 8403852 A NL8403852 A NL 8403852A
- Authority
- NL
- Netherlands
- Prior art keywords
- amino
- methoxymitosane
- compound
- mitomycin
- substituted
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 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 claims description 116
- 150000001875 compounds Chemical class 0.000 claims description 68
- 229960004857 mitomycin Drugs 0.000 claims description 56
- -1 2-chloroacetyl Chemical group 0.000 claims description 27
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 10
- 125000000129 anionic group Chemical group 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 239000003495 polar organic solvent Substances 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 1
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 22
- 238000012360 testing method Methods 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
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- 239000000126 substance Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 6
- 239000004533 oil dispersion Substances 0.000 description 6
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 6
- JUJWROOIHBZHMG-QYKNYGDISA-N 2-deuteriopyridine Chemical compound [2H]C1=CC=CC=N1 JUJWROOIHBZHMG-QYKNYGDISA-N 0.000 description 5
- 229930192392 Mitomycin Natural products 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 208000001382 Experimental Melanoma Diseases 0.000 description 4
- HYFMSAFINFJTFH-UHFFFAOYSA-N Mitomycin-A Natural products O=C1C(OC)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)N2CC2NC21 HYFMSAFINFJTFH-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 235000011089 carbon dioxide Nutrition 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- HYFMSAFINFJTFH-NGSRAFSJSA-N mitomycin A Chemical compound O=C1C(OC)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@]1(OC)N2C[C@@H]2N[C@@H]21 HYFMSAFINFJTFH-NGSRAFSJSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 150000008064 anhydrides Chemical group 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VHBFEIBMZHEWSX-UHFFFAOYSA-N 2-isothiocyanatopropane Chemical group CC(C)N=C=S VHBFEIBMZHEWSX-UHFFFAOYSA-N 0.000 description 2
- LOLKAJARZKDJTD-UHFFFAOYSA-N 4-Ethoxy-4-oxobutanoic acid Chemical compound CCOC(=O)CCC(O)=O LOLKAJARZKDJTD-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 2
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- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000005595 deprotonation Effects 0.000 description 2
- 238000010537 deprotonation reaction Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
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- 230000005764 inhibitory process Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 230000003039 myelosuppressive effect Effects 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
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- 150000003672 ureas Chemical class 0.000 description 2
- JFOIBTLTZWOAIC-UHFFFAOYSA-N (4-nitrophenyl) 2,2,2-trifluoroacetate Chemical compound [O-][N+](=O)C1=CC=C(OC(=O)C(F)(F)F)C=C1 JFOIBTLTZWOAIC-UHFFFAOYSA-N 0.000 description 1
- GMKZBFFLCONHDE-UHFFFAOYSA-N (4-nitrophenyl) benzoate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)C1=CC=CC=C1 GMKZBFFLCONHDE-UHFFFAOYSA-N 0.000 description 1
- FFGGSHSHUKFELB-UHFFFAOYSA-N (4-nitrophenyl) methanesulfonate Chemical compound CS(=O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 FFGGSHSHUKFELB-UHFFFAOYSA-N 0.000 description 1
- NSBVDAMBDUXZAS-UHFFFAOYSA-N (4-nitrophenyl)methyl n-ethylcarbamate Chemical compound CCNC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 NSBVDAMBDUXZAS-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- RMQSINXLELHUAE-UHFFFAOYSA-N 1-[chloro(ethylsulfanyl)phosphoryl]oxyethane Chemical compound CCOP(Cl)(=O)SCC RMQSINXLELHUAE-UHFFFAOYSA-N 0.000 description 1
- BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-RHQRLBAQSA-N 2,3,4,5-tetradeuteriopyridine Chemical compound [2H]C1=CN=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RHQRLBAQSA-N 0.000 description 1
- AHDSRXYHVZECER-UHFFFAOYSA-N 2,4,6-tris[(dimethylamino)methyl]phenol Chemical compound CN(C)CC1=CC(CN(C)C)=C(O)C(CN(C)C)=C1 AHDSRXYHVZECER-UHFFFAOYSA-N 0.000 description 1
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- HNQRPLGPFCZIDQ-UHFFFAOYSA-N 3-benzyl-1-hydroxypyrrolidine-2,5-dione;carbonic acid Chemical compound OC(O)=O.O=C1N(O)C(=O)CC1CC1=CC=CC=C1 HNQRPLGPFCZIDQ-UHFFFAOYSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
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- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
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- UZUUQCBCWDBYCG-UHFFFAOYSA-N Mitomycin B Natural products O=C1C(OC)=C(C)C(=O)C2=C1C(COC(N)=O)C1(O)N2CC2C1N2C UZUUQCBCWDBYCG-UHFFFAOYSA-N 0.000 description 1
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Mitomycin E Natural products O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
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- 206010070863 Toxicity to various agents Diseases 0.000 description 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- UZUUQCBCWDBYCG-DQRAMIIBSA-N mitomycin B Chemical compound O=C1C(OC)=C(C)C(=O)C2=C1[C@H](COC(N)=O)[C@]1(O)N2C[C@H]2[C@@H]1N2C UZUUQCBCWDBYCG-DQRAMIIBSA-N 0.000 description 1
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- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- VVWNENUJKRQDTB-UHFFFAOYSA-N o-ethyl methanethioate Chemical compound CCOC=S VVWNENUJKRQDTB-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000005677 organic carbonates Chemical class 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- LCCNCVORNKJIRZ-UHFFFAOYSA-N parathion Chemical compound CCOP(=S)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 LCCNCVORNKJIRZ-UHFFFAOYSA-N 0.000 description 1
- AGUWUIVKDXDKBT-UHFFFAOYSA-N phenyl 2-chloroacetate Chemical compound ClCC(=O)OC1=CC=CC=C1 AGUWUIVKDXDKBT-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- HDGICZVUXOQTPV-UHFFFAOYSA-N phenylsulfanyl acetate Chemical compound CC(=O)OSC1=CC=CC=C1 HDGICZVUXOQTPV-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003566 thiocarboxylic acids Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 230000001875 tumorinhibitory effect Effects 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/564,806 US4642352A (en) | 1983-12-23 | 1983-12-23 | Acylamino mitosanes |
US56480683 | 1983-12-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
NL8403852A true NL8403852A (nl) | 1985-07-16 |
Family
ID=24255968
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NL8403852A NL8403852A (nl) | 1983-12-23 | 1984-12-19 | Acylamino mitosanen; werkwijze voor het bereiden daarvan. |
Country Status (32)
Country | Link |
---|---|
US (1) | US4642352A (es) |
JP (1) | JPS60169481A (es) |
KR (1) | KR910009329B1 (es) |
AR (1) | AR244231A1 (es) |
AT (1) | AT386828B (es) |
AU (1) | AU561376B2 (es) |
BE (1) | BE901377A (es) |
CA (1) | CA1239645A (es) |
CH (1) | CH665641A5 (es) |
DD (1) | DD228259A5 (es) |
DE (1) | DE3447003C2 (es) |
DK (1) | DK169477B1 (es) |
ES (1) | ES538804A0 (es) |
FI (1) | FI81099C (es) |
FR (1) | FR2557112B1 (es) |
GB (1) | GB2151627B (es) |
GR (1) | GR82567B (es) |
HU (1) | HU193245B (es) |
IE (1) | IE57835B1 (es) |
IL (1) | IL73876A (es) |
IT (1) | IT1178792B (es) |
LU (1) | LU85711A1 (es) |
MY (1) | MY100976A (es) |
NL (1) | NL8403852A (es) |
NO (1) | NO163570C (es) |
NZ (1) | NZ210254A (es) |
OA (1) | OA07911A (es) |
PT (1) | PT79741B (es) |
SE (1) | SE8406577L (es) |
SU (1) | SU1364239A3 (es) |
YU (1) | YU45688B (es) |
ZA (1) | ZA849907B (es) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4487769A (en) * | 1982-06-04 | 1984-12-11 | Bristol-Myers Company | Amidines |
NZ206932A (en) * | 1983-02-07 | 1987-08-31 | University Patents Inc | Certain 6-(heterocyclyl or amino) mitosanes and pharmaceutical compositions |
US4803212A (en) * | 1983-04-11 | 1989-02-07 | Bristol-Myers Company | Amino disulfides |
FR2571373A1 (fr) * | 1984-10-09 | 1986-04-11 | Bristol Myers Co | Procede de preparation de derives n7-substitues de la mitomycine c |
CA1282069C (en) * | 1985-09-12 | 1991-03-26 | Damon L. Meyer | Antibody complexes of hapten-modified diagnostic or therapeutic agents |
JPS6354380A (ja) * | 1986-08-26 | 1988-03-08 | Kyowa Hakko Kogyo Co Ltd | マイトマイシン誘導体 |
ZA886812B (en) * | 1987-11-23 | 1989-07-26 | Bristol Myers Co | Anti-tumor prodrugs |
US4874779A (en) * | 1988-06-29 | 1989-10-17 | Bristol-Myers Company | Mitomycin phosphate derivatives |
US5214804A (en) * | 1992-01-27 | 1993-06-01 | Carey Michael J | Protective mask with scarf |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US27384A (en) * | 1860-03-06 | Slide-valve for steam-engines | ||
BE655399A (es) * | ||||
CA771155A (en) * | 1967-11-07 | Matsui Masanao | Phosphorus-containing derivatives of mitomycin c | |
US3660578A (en) * | 1957-04-06 | 1972-05-02 | Kyowa Hakko Kogyo Kk | Mitomycin c |
NL129868C (es) * | 1963-06-07 | |||
DE1570029A1 (de) * | 1964-07-09 | 1970-04-09 | Kyowa Hakko Kogyo Kk | Verfahren zur Herstellung von Mitosanverbindungen |
US3420846A (en) * | 1964-08-25 | 1969-01-07 | Kyowa Hakko Kogyo Kk | 7-substituted mitomycin a |
US3332944A (en) * | 1964-11-02 | 1967-07-25 | American Cyanamid Co | Antibiotic derivatives of mitomycins a, b, c and porfiromycin |
FR1540921A (fr) * | 1965-05-18 | 1968-10-04 | Kyowa Hakko Kogyo Kk | Procédé de préparation de dérivés de thio-urée de la mitomycine c |
US3410867A (en) * | 1965-11-22 | 1968-11-12 | Kyowa Hakko Kogyo Kk | Mitomycin derivatives |
JPS5439098A (en) * | 1977-08-31 | 1979-03-24 | Kyowa Hakko Kogyo Co Ltd | Mitomycin c derivatives |
EP0008021B1 (en) * | 1978-07-18 | 1984-05-16 | Kyowa Hakko Kogyo Co., Ltd | New mitomycins and processes for production thereof |
US4268676A (en) * | 1979-12-05 | 1981-05-19 | University Patents, Inc. | Mitomycin analogs |
US4444768A (en) * | 1980-03-04 | 1984-04-24 | Ciba-Geigy Corporation | Pyrimido[1,6-a]indoles, pharmaceutical preparations containing them, and methods of treating pain and inflammation with them |
NZ199617A (en) * | 1981-05-15 | 1985-08-30 | University Patents Inc | Azirino(2',3',:3,4)pyrrolo(1,2-a)indole-4,7-dione derivatives and pharmaceutical compositions |
JPS58201791A (ja) | 1982-05-19 | 1983-11-24 | Katsuo Unno | ヘマトポルフイリン誘導体 |
US4487769A (en) * | 1982-06-04 | 1984-12-11 | Bristol-Myers Company | Amidines |
-
1983
- 1983-12-23 US US06/564,806 patent/US4642352A/en not_active Expired - Fee Related
-
1984
- 1984-11-20 AU AU35710/84A patent/AU561376B2/en not_active Ceased
- 1984-11-20 NZ NZ210254A patent/NZ210254A/en unknown
- 1984-12-06 AR AR84298866A patent/AR244231A1/es active
- 1984-12-11 FR FR8418904A patent/FR2557112B1/fr not_active Expired
- 1984-12-12 CA CA000469874A patent/CA1239645A/en not_active Expired
- 1984-12-19 NO NO845100A patent/NO163570C/no unknown
- 1984-12-19 FI FI845037A patent/FI81099C/fi not_active IP Right Cessation
- 1984-12-19 ZA ZA849907A patent/ZA849907B/xx unknown
- 1984-12-19 YU YU215284A patent/YU45688B/sh unknown
- 1984-12-19 NL NL8403852A patent/NL8403852A/nl not_active Application Discontinuation
- 1984-12-19 ES ES538804A patent/ES538804A0/es active Granted
- 1984-12-20 CH CH6091/84A patent/CH665641A5/de not_active IP Right Cessation
- 1984-12-20 IL IL73876A patent/IL73876A/xx not_active IP Right Cessation
- 1984-12-21 BE BE0/214237A patent/BE901377A/fr not_active IP Right Cessation
- 1984-12-21 LU LU85711A patent/LU85711A1/fr unknown
- 1984-12-21 AT AT0407484A patent/AT386828B/de not_active IP Right Cessation
- 1984-12-21 OA OA58488A patent/OA07911A/xx unknown
- 1984-12-21 IE IE3318/84A patent/IE57835B1/en not_active IP Right Cessation
- 1984-12-21 DD DD84271473A patent/DD228259A5/de not_active IP Right Cessation
- 1984-12-21 DE DE3447003A patent/DE3447003C2/de not_active Expired - Fee Related
- 1984-12-21 JP JP59268757A patent/JPS60169481A/ja active Granted
- 1984-12-21 HU HU844801A patent/HU193245B/hu not_active IP Right Cessation
- 1984-12-21 PT PT79741A patent/PT79741B/pt not_active IP Right Cessation
- 1984-12-21 SE SE8406577A patent/SE8406577L/xx unknown
- 1984-12-21 GB GB08432513A patent/GB2151627B/en not_active Expired
- 1984-12-21 SU SU843826167A patent/SU1364239A3/ru active
- 1984-12-21 DK DK621484A patent/DK169477B1/da active
- 1984-12-21 GR GR82567A patent/GR82567B/el unknown
- 1984-12-21 IT IT24227/84A patent/IT1178792B/it active
- 1984-12-22 KR KR1019840008275A patent/KR910009329B1/ko not_active IP Right Cessation
-
1987
- 1987-09-29 MY MYPI87002232A patent/MY100976A/en unknown
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Legal Events
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DNT | Communications of changes of names of applicants whose applications have been laid open to public inspection |
Free format text: BRISTOL-MYERS SQUIBB COMPANY |
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BA | A request for search or an international-type search has been filed | ||
BB | A search report has been drawn up | ||
BC | A request for examination has been filed | ||
BV | The patent application has lapsed |