JPS624398B2 - - Google Patents
Info
- Publication number
- JPS624398B2 JPS624398B2 JP52108344A JP10834477A JPS624398B2 JP S624398 B2 JPS624398 B2 JP S624398B2 JP 52108344 A JP52108344 A JP 52108344A JP 10834477 A JP10834477 A JP 10834477A JP S624398 B2 JPS624398 B2 JP S624398B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound according
- hydrogen
- carboxamide
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 31
- -1 (2-stearoyloxyethyl)carboxamide Chemical compound 0.000 claims description 29
- 206010028980 Neoplasm Diseases 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 150000003857 carboxamides Chemical class 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 14
- 150000002431 hydrogen Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- SSQTXMAIJVOVIP-UHFFFAOYSA-N n-(2-methoxyethyl)formamide Chemical compound COCCNC=O SSQTXMAIJVOVIP-UHFFFAOYSA-N 0.000 claims description 8
- ZNAHFSQAXSOVLF-UHFFFAOYSA-N 2,3-dihydro-1h-indole-2-carboxamide;1h-indole Chemical compound C1=CC=C2NC=CC2=C1.C1=CC=C2NC(C(=O)N)CC2=C1 ZNAHFSQAXSOVLF-UHFFFAOYSA-N 0.000 claims description 7
- JRZBPELLUMBLQU-UHFFFAOYSA-N carbonazidic acid Chemical compound OC(=O)N=[N+]=[N-] JRZBPELLUMBLQU-UHFFFAOYSA-N 0.000 claims description 7
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 6
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims description 6
- 125000002228 disulfide group Chemical group 0.000 claims description 5
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 5
- 125000005193 alkenylcarbonyloxy group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 claims description 3
- QPYIBQMRTUNZHZ-UHFFFAOYSA-N 2-formamidoethyl prop-2-enoate Chemical compound C=CC(=O)OCCNC=O QPYIBQMRTUNZHZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
- DSOBFWPMWSXZGI-UHFFFAOYSA-N (3-amino-3-oxopropyl) acetate Chemical compound CC(=O)OCCC(N)=O DSOBFWPMWSXZGI-UHFFFAOYSA-N 0.000 claims 1
- BHPBDSRHYYCQQO-UHFFFAOYSA-N 3-acetamidopropanamide Chemical compound CC(=O)NCCC(N)=O BHPBDSRHYYCQQO-UHFFFAOYSA-N 0.000 claims 1
- UJCYEHJOKQZZHG-UHFFFAOYSA-N 3-methylsulfanylpropanamide Chemical compound CSCCC(N)=O UJCYEHJOKQZZHG-UHFFFAOYSA-N 0.000 claims 1
- JLSJEUQOXVVCPN-UHFFFAOYSA-N 3-sulfanylpropanamide Chemical compound NC(=O)CCS JLSJEUQOXVVCPN-UHFFFAOYSA-N 0.000 claims 1
- JCERQDSYEXAYTH-UHFFFAOYSA-N 4-methylsulfanylbutanamide Chemical compound CSCCCC(N)=O JCERQDSYEXAYTH-UHFFFAOYSA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical class C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 88
- 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 82
- 241000699670 Mus sp. Species 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 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 17
- 150000001540 azides Chemical class 0.000 description 15
- 238000001819 mass spectrum Methods 0.000 description 15
- 239000000843 powder Substances 0.000 description 14
- 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 14
- 150000001408 amides Chemical class 0.000 description 13
- 230000000704 physical effect Effects 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 150000001793 charged compounds Chemical class 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 230000004083 survival effect Effects 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 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
- 239000002253 acid Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229930013930 alkaloid Natural products 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- GDENSQSVDRFGSZ-UHFFFAOYSA-N n-(2-sulfanylethyl)formamide Chemical compound SCCNC=O GDENSQSVDRFGSZ-UHFFFAOYSA-N 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 229960003048 vinblastine Drugs 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000012046 mixed solvent Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000009036 growth inhibition Effects 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 208000032839 leukemia Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- UKTNDLHXQNQKBH-UHFFFAOYSA-N 2,3-dihydro-1h-indole;1h-indole Chemical class C1=CC=C2NCCC2=C1.C1=CC=C2NC=CC2=C1 UKTNDLHXQNQKBH-UHFFFAOYSA-N 0.000 description 4
- 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
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000007796 conventional method Methods 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
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Natural products CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- LHUZAYREVYDAGJ-UHFFFAOYSA-N dichloromethane;ethyl acetate;methanol Chemical compound OC.ClCCl.CCOC(C)=O LHUZAYREVYDAGJ-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 229960004528 vincristine Drugs 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- PYXDKYYHNBADTF-UHFFFAOYSA-N 2-formamidoethyl acetate Chemical compound CC(=O)OCCNC=O PYXDKYYHNBADTF-UHFFFAOYSA-N 0.000 description 2
- KKYSBGWCYXYOHA-UHFFFAOYSA-N 3-methylthiopropylamine Chemical compound CSCCCN KKYSBGWCYXYOHA-UHFFFAOYSA-N 0.000 description 2
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 240000001829 Catharanthus roseus Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- WVTGEXAIVZDLCR-UHFFFAOYSA-N Vindoline Natural products CC1C2CN3CCCC14CCC5Nc6ccccc6C25C34 WVTGEXAIVZDLCR-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 2
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- GKWYINOZGDHWRA-UHFFFAOYSA-N catharanthine Natural products C1C(CC)(O)CC(CC2C(=O)OC)CN1CCC1=C2NC2=CC=CC=C12 GKWYINOZGDHWRA-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- VAFIWTIWOOZYCZ-UHFFFAOYSA-N n-(2-aminoethyl)formamide Chemical compound NCCNC=O VAFIWTIWOOZYCZ-UHFFFAOYSA-N 0.000 description 2
- ANIOBYVVCVYSCX-UHFFFAOYSA-N n-(2-methylsulfanylethyl)formamide Chemical compound CSCCNC=O ANIOBYVVCVYSCX-UHFFFAOYSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 150000003140 primary amides Chemical class 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- CXBGOBGJHGGWIE-IYJDUVQVSA-N vindoline Chemical compound CN([C@H]1[C@](O)([C@@H]2OC(C)=O)C(=O)OC)C3=CC(OC)=CC=C3[C@]11CCN3CC=C[C@]2(CC)[C@@H]13 CXBGOBGJHGGWIE-IYJDUVQVSA-N 0.000 description 2
- AFENDNXGAFYKQO-VKHMYHEASA-N (S)-2-hydroxybutyric acid Chemical compound CC[C@H](O)C(O)=O AFENDNXGAFYKQO-VKHMYHEASA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
- YSWFMQGCLBXBHU-UHFFFAOYSA-N 2-aminoethyl butanoate Chemical compound CCCC(=O)OCCN YSWFMQGCLBXBHU-UHFFFAOYSA-N 0.000 description 1
- UGIJCMNGQCUTPI-UHFFFAOYSA-N 2-aminoethyl prop-2-enoate Chemical compound NCCOC(=O)C=C UGIJCMNGQCUTPI-UHFFFAOYSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- BPGIOCZAQDIBPI-UHFFFAOYSA-N 2-ethoxyethanamine Chemical compound CCOCCN BPGIOCZAQDIBPI-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- UANWURKQKKYIGV-UHFFFAOYSA-N 2-methoxypropan-1-amine Chemical compound COC(C)CN UANWURKQKKYIGV-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
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- 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
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- 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)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical 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 |
|---|---|
| JPS5340799A JPS5340799A (en) | 1978-04-13 |
| JPS624398B2 true JPS624398B2 (pl) | 1987-01-30 |
Family
ID=24898757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10834477A Granted JPS5340799A (en) | 1976-09-08 | 1977-09-08 | Novel amide derivative of dimer alkaloid |
Country Status (27)
| Country | Link |
|---|---|
| JP (1) | JPS5340799A (pl) |
| AR (3) | AR226411A1 (pl) |
| AT (1) | AT360513B (pl) |
| AU (1) | AU511055B2 (pl) |
| BE (1) | BE858451A (pl) |
| CA (1) | CA1082179A (pl) |
| CH (1) | CH631990A5 (pl) |
| DD (1) | DD133055A5 (pl) |
| DE (1) | DE2739443A1 (pl) |
| DK (1) | DK146822C (pl) |
| ES (1) | ES462229A1 (pl) |
| FR (1) | FR2364220A1 (pl) |
| GB (1) | GB1586709A (pl) |
| GR (1) | GR69783B (pl) |
| HU (1) | HU180722B (pl) |
| IE (1) | IE45558B1 (pl) |
| IL (1) | IL52731A0 (pl) |
| MX (1) | MX4740E (pl) |
| NL (1) | NL7709806A (pl) |
| NZ (1) | NZ184932A (pl) |
| PH (1) | PH14771A (pl) |
| PL (1) | PL104309B1 (pl) |
| PT (1) | PT66984B (pl) |
| RO (3) | RO77922A (pl) |
| SE (1) | SE434953B (pl) |
| YU (1) | YU209777A (pl) |
| ZA (1) | ZA774988B (pl) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE30561E (en) * | 1976-12-06 | 1981-03-31 | Eli Lilly And Company | Vinca alkaloid intermediates |
| US4199504A (en) * | 1978-05-15 | 1980-04-22 | Eli Lilly And Company | Bridged cathranthus alkaloid dimers |
| AR225153A1 (es) * | 1978-10-10 | 1982-02-26 | Lilly Co Eli | Un procedimiento para la preparacion de sulfato de vindesina |
| US4357334A (en) | 1980-03-20 | 1982-11-02 | Eli Lilly And Company | Use of VLB 3-(2-chloroethyl) carboxamide in treating neoplasms |
| OA06421A (fr) * | 1980-06-10 | 1981-09-30 | Omnium Chimique Sa | Procédé de préparation de dérivés N-(vinblastinoyl-23) d'acides aminés et de peptides. |
| US4362664A (en) * | 1980-12-29 | 1982-12-07 | Eli Lilly And Company | Vinblastine oxazolidinedione disulfides and related compounds |
| CA1335686C (fr) * | 1986-01-13 | 1995-05-23 | Rao K. S. P. Bhushana | Vinblastine et composition pharmaceutique les contenant |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR204004A1 (es) * | 1973-04-02 | 1975-11-12 | Lilly Co Eli | Procedimientos para preparar derivados de vinblastina leurosidina y leurocristina |
| IL48685A (en) * | 1975-01-09 | 1980-03-31 | Lilly Co Eli | Amides of vincadioline and vinblastine |
-
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 IE IE1700/77A patent/IE45558B1/en not_active IP Right Cessation
- 1977-08-15 CA CA284,711A patent/CA1082179A/en not_active Expired
- 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 AR AR269062A patent/AR226411A1/es active
- 1977-09-01 PT PT66984A patent/PT66984B/pt unknown
- 1977-09-01 PL PL1977200607A patent/PL104309B1/pl not_active IP Right Cessation
- 1977-09-01 DE DE19772739443 patent/DE2739443A1/de active Granted
- 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 CH CH1089377A patent/CH631990A5/de not_active IP Right Cessation
- 1977-09-06 NL NL7709806A patent/NL7709806A/xx not_active Application Discontinuation
- 1977-09-06 RO RO7798857A patent/RO77922A/ro unknown
- 1977-09-06 RO RO7798856A patent/RO77921A/ro unknown
- 1977-09-07 BE BE1008362A patent/BE858451A/xx not_active IP Right Cessation
- 1977-09-07 DK DK398577A patent/DK146822C/da not_active IP Right Cessation
- 1977-09-07 RO RO7791544A patent/RO72474A/ro unknown
- 1977-09-07 AT AT644277A patent/AT360513B/de not_active IP Right Cessation
- 1977-09-07 FR FR7727080A patent/FR2364220A1/fr active Granted
- 1977-09-07 MX MX776104U patent/MX4740E/es unknown
- 1977-09-07 HU HU77EI762A patent/HU180722B/hu unknown
- 1977-09-07 SE SE7710059A patent/SE434953B/xx not_active IP Right Cessation
- 1977-09-08 JP JP10834477A patent/JPS5340799A/ja active Granted
- 1977-09-08 DD DD7700200940A patent/DD133055A5/xx unknown
- 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
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