DE2739443A1 - Dimere indol-dihydroindolcarboxamide, verfahren zu ihrer herstellung und ihre verwendung - Google Patents
Dimere indol-dihydroindolcarboxamide, verfahren zu ihrer herstellung und ihre verwendungInfo
- Publication number
- DE2739443A1 DE2739443A1 DE19772739443 DE2739443A DE2739443A1 DE 2739443 A1 DE2739443 A1 DE 2739443A1 DE 19772739443 DE19772739443 DE 19772739443 DE 2739443 A DE2739443 A DE 2739443A DE 2739443 A1 DE2739443 A1 DE 2739443A1
- Authority
- DE
- Germany
- Prior art keywords
- group
- vlb
- deacetyl
- compounds according
- general formula
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims description 26
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 58
- 150000001875 compounds Chemical class 0.000 claims description 45
- 150000003839 salts Chemical class 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 13
- 150000003857 carboxamides Chemical class 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- GDENSQSVDRFGSZ-UHFFFAOYSA-N n-(2-sulfanylethyl)formamide Chemical compound SCCNC=O GDENSQSVDRFGSZ-UHFFFAOYSA-N 0.000 claims description 10
- ZNAHFSQAXSOVLF-UHFFFAOYSA-N 2,3-dihydro-1h-indole-2-carboxamide;1h-indole Chemical class C1=CC=C2NC=CC2=C1.C1=CC=C2NC(C(=O)N)CC2=C1 ZNAHFSQAXSOVLF-UHFFFAOYSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- SSQTXMAIJVOVIP-UHFFFAOYSA-N n-(2-methoxyethyl)formamide Chemical compound COCCNC=O SSQTXMAIJVOVIP-UHFFFAOYSA-N 0.000 claims description 7
- KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 4
- 239000012876 carrier material Substances 0.000 claims description 4
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims description 4
- 239000000539 dimer Substances 0.000 claims description 4
- PYXDKYYHNBADTF-UHFFFAOYSA-N 2-formamidoethyl acetate Chemical compound CC(=O)OCCNC=O PYXDKYYHNBADTF-UHFFFAOYSA-N 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- UKTNDLHXQNQKBH-UHFFFAOYSA-N 2,3-dihydro-1h-indole;1h-indole Chemical compound C1=CC=C2NCCC2=C1.C1=CC=C2NC=CC2=C1 UKTNDLHXQNQKBH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- SDAYLWNCGSHFTH-UHFFFAOYSA-N n-(3-methylsulfanylpropyl)formamide Chemical compound CSCCCNC=O SDAYLWNCGSHFTH-UHFFFAOYSA-N 0.000 claims description 2
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- 229960003048 vinblastine Drugs 0.000 description 42
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- 239000000243 solution Substances 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- -1 isobutyryl group Chemical group 0.000 description 24
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- 238000002329 infrared spectrum Methods 0.000 description 15
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- 239000000203 mixture Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
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- 239000011541 reaction mixture Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
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- 239000002585 base Substances 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 229930013930 alkaloid Natural products 0.000 description 6
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- 238000001819 mass spectrum Methods 0.000 description 6
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 6
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000003368 amide group Chemical group 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
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- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000011877 solvent mixture Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 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 description 4
- 230000000118 anti-neoplastic effect Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- BAMUPQJDKBGDPU-UHFFFAOYSA-N n-(2-hydroxyethyl)formamide Chemical compound OCCNC=O BAMUPQJDKBGDPU-UHFFFAOYSA-N 0.000 description 4
- 230000001613 neoplastic effect Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
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- 235000010288 sodium nitrite Nutrition 0.000 description 4
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- 238000001228 spectrum Methods 0.000 description 4
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- 230000002588 toxic effect Effects 0.000 description 4
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- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
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- 238000004458 analytical method Methods 0.000 description 3
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- 235000011152 sodium sulphate Nutrition 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
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- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
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- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical class OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 239000000314 lubricant Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 125000004492 methyl ester group Chemical group 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001419 myristoyl group Chemical group O=C([*])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([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ANIOBYVVCVYSCX-UHFFFAOYSA-N n-(2-methylsulfanylethyl)formamide Chemical compound CSCCNC=O ANIOBYVVCVYSCX-UHFFFAOYSA-N 0.000 description 1
- YWCWBUHJAURDMV-UHFFFAOYSA-N n-ethylformamide;sulfuric acid Chemical compound CCNC=O.OS(O)(=O)=O YWCWBUHJAURDMV-UHFFFAOYSA-N 0.000 description 1
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 1
- 235000019392 nitrosyl chloride Nutrition 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])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([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UDMDNOFKRFLVIA-UHFFFAOYSA-N propanamide sulfuric acid Chemical compound S(=O)(=O)(O)O.C(CC)(=O)N UDMDNOFKRFLVIA-UHFFFAOYSA-N 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([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([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical class OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 239000004552 water soluble powder Substances 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72165076A | 1976-09-08 | 1976-09-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2739443A1 true DE2739443A1 (de) | 1978-03-09 |
| DE2739443C2 DE2739443C2 (enrdf_load_stackoverflow) | 1991-08-14 |
Family
ID=24898757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19772739443 Granted DE2739443A1 (de) | 1976-09-08 | 1977-09-01 | Dimere indol-dihydroindolcarboxamide, verfahren zu ihrer herstellung und ihre verwendung |
Country Status (27)
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0005620A1 (en) * | 1978-05-15 | 1979-11-28 | Eli Lilly And Company | Bridged catharanthus alkaloid dimers, their preparation and formulations containing them |
| EP0009996A1 (en) * | 1978-10-10 | 1980-04-16 | Eli Lilly And Company | Preparation of vindesine monosulfate |
| EP0055602A3 (en) * | 1980-12-29 | 1982-10-13 | Eli Lilly And Company | Oxazolidinedione sulfide compounds |
| US4357334A (en) | 1980-03-20 | 1982-11-02 | Eli Lilly And Company | Use of VLB 3-(2-chloroethyl) carboxamide in treating neoplasms |
| US4388305A (en) * | 1980-06-10 | 1983-06-14 | Omnichem S.A. | Vinblastin-23-oyl amino acid derivatives for use as antitumor agents |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE30561E (en) * | 1976-12-06 | 1981-03-31 | Eli Lilly And Company | Vinca alkaloid intermediates |
| US4831038A (en) * | 1986-01-13 | 1989-05-16 | Ire-Celltarg S.A. | Vinblastine derivatives and pharmaceutical composition containing them |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2415980A1 (de) * | 1973-04-02 | 1974-10-10 | Lilly Co Eli | Neue aminderivate von vinblastin, leurosidin und leurocristin und verfahren zu ihrer herstellung |
| DE2558027A1 (de) * | 1975-01-09 | 1976-07-15 | Lilly Co Eli | Amidderivate von vinblastin, leurosidin, leurocristin und damit verwandten dimeren alkaloiden sowie verfahren zu ihrer herstellung |
-
1977
- 1977-08-10 GR GR54126A patent/GR69783B/el unknown
- 1977-08-15 IL IL52731A patent/IL52731A0/xx not_active IP Right Cessation
- 1977-08-15 CA CA284,711A patent/CA1082179A/en not_active Expired
- 1977-08-15 IE IE1700/77A patent/IE45558B1/en not_active IP Right Cessation
- 1977-08-16 NZ NZ184932A patent/NZ184932A/xx unknown
- 1977-08-17 ZA ZA00774988A patent/ZA774988B/xx unknown
- 1977-08-19 AU AU28039/77A patent/AU511055B2/en not_active Expired
- 1977-09-01 DE DE19772739443 patent/DE2739443A1/de active Granted
- 1977-09-01 PT PT66984A patent/PT66984B/pt unknown
- 1977-09-01 AR AR269062A patent/AR226411A1/es active
- 1977-09-01 PL PL1977200607A patent/PL104309B1/pl not_active IP Right Cessation
- 1977-09-02 GB GB36691/77A patent/GB1586709A/en not_active Expired
- 1977-09-02 YU YU02097/77A patent/YU209777A/xx unknown
- 1977-09-02 PH PH20192A patent/PH14771A/en unknown
- 1977-09-06 NL NL7709806A patent/NL7709806A/xx not_active Application Discontinuation
- 1977-09-06 CH CH1089377A patent/CH631990A5/de not_active IP Right Cessation
- 1977-09-06 RO RO7798857A patent/RO77922A/ro unknown
- 1977-09-06 RO RO7798856A patent/RO77921A/ro unknown
- 1977-09-07 HU HU77EI762A patent/HU180722B/hu unknown
- 1977-09-07 AT AT644277A patent/AT360513B/de not_active IP Right Cessation
- 1977-09-07 DK DK398577A patent/DK146822C/da not_active IP Right Cessation
- 1977-09-07 MX MX776104U patent/MX4740E/es unknown
- 1977-09-07 BE BE1008362A patent/BE858451A/xx not_active IP Right Cessation
- 1977-09-07 SE SE7710059A patent/SE434953B/xx not_active IP Right Cessation
- 1977-09-07 RO RO7791544A patent/RO72474A/ro unknown
- 1977-09-07 FR FR7727080A patent/FR2364220A1/fr active Granted
- 1977-09-08 DD DD7700200940A patent/DD133055A5/xx unknown
- 1977-09-08 JP JP10834477A patent/JPS5340799A/ja active Granted
- 1977-09-08 ES ES462229A patent/ES462229A1/es not_active Expired
-
1979
- 1979-07-25 AR AR277456A patent/AR231643A1/es active
- 1979-07-25 AR AR277455A patent/AR230642A1/es active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2415980A1 (de) * | 1973-04-02 | 1974-10-10 | Lilly Co Eli | Neue aminderivate von vinblastin, leurosidin und leurocristin und verfahren zu ihrer herstellung |
| DE2558027A1 (de) * | 1975-01-09 | 1976-07-15 | Lilly Co Eli | Amidderivate von vinblastin, leurosidin, leurocristin und damit verwandten dimeren alkaloiden sowie verfahren zu ihrer herstellung |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0005620A1 (en) * | 1978-05-15 | 1979-11-28 | Eli Lilly And Company | Bridged catharanthus alkaloid dimers, their preparation and formulations containing them |
| EP0032756A3 (en) * | 1978-05-15 | 1981-09-09 | Eli Lilly And Company | Intermediates used in the preparation of bridged catharanthus alkaloid dimers |
| EP0033981A3 (en) * | 1978-05-15 | 1981-09-09 | Eli Lilly And Company | Preparation of bridged catharanthus alkaloid dimers |
| EP0009996A1 (en) * | 1978-10-10 | 1980-04-16 | Eli Lilly And Company | Preparation of vindesine monosulfate |
| US4357334A (en) | 1980-03-20 | 1982-11-02 | Eli Lilly And Company | Use of VLB 3-(2-chloroethyl) carboxamide in treating neoplasms |
| US4388305A (en) * | 1980-06-10 | 1983-06-14 | Omnichem S.A. | Vinblastin-23-oyl amino acid derivatives for use as antitumor agents |
| EP0055602A3 (en) * | 1980-12-29 | 1982-10-13 | Eli Lilly And Company | Oxazolidinedione sulfide compounds |
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