JPS624398B2 - - Google Patents

Info

Publication number: JPS624398B2
Authority: JP; Japan
Prior art keywords: formula; compound according; hydrogen; carboxamide; compound
Prior art date: 1976-09-08
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

Application number

JP52108344A

Other languages

English (en)

Japanese (ja)

Other versions

JPS5340799A (en

Inventor

Jei Karinan Jooji

Geruzon Kooruto

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eli Lilly and Co

Original Assignee

Eli Lilly and 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.)

1976-09-08

Filing date

1977-09-08

Publication date

1987-01-30

1977-09-08 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1978-04-13 Publication of JPS5340799A publication Critical patent/JPS5340799A/ja

1987-01-30 Publication of JPS624398B2 publication Critical patent/JPS624398B2/ja

Status Granted legal-status Critical Current

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
CYWGSFFHHMQKET-UHFFFAOYSA-N 2-methylsulfanylethanamine Chemical compound CSCCN CYWGSFFHHMQKET-UHFFFAOYSA-N 0.000 description 1
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DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
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KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound 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-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
238000000746 purification Methods 0.000 description 1
SBMSLRMNBSMKQC-UHFFFAOYSA-N pyrrolidin-1-amine Chemical compound NN1CCCC1 SBMSLRMNBSMKQC-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical class O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
150000003334 secondary amides Chemical class 0.000 description 1
239000011780 sodium chloride 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
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 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
229940124597 therapeutic agent Drugs 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
238000004448 titration Methods 0.000 description 1
231100000167 toxic agent Toxicity 0.000 description 1
239000003440 toxic substance Substances 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
229940066528 trichloroacetate Drugs 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
HHJUWIANJFBDHT-KOTLKJBCSA-N vindesine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(N)=O)N4C)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 HHJUWIANJFBDHT-KOTLKJBCSA-N 0.000 description 1
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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

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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)

JP10834477A 1976-09-08 1977-09-08 Novel amide derivative of dimer alkaloid Granted JPS5340799A (en)

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 (de)	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 (de)
AR (3)	AR226411A1 (de)
AT (1)	AT360513B (de)
AU (1)	AU511055B2 (de)
BE (1)	BE858451A (de)
CA (1)	CA1082179A (de)
CH (1)	CH631990A5 (de)
DD (1)	DD133055A5 (de)
DE (1)	DE2739443A1 (de)
DK (1)	DK146822C (de)
ES (1)	ES462229A1 (de)
FR (1)	FR2364220A1 (de)
GB (1)	GB1586709A (de)
GR (1)	GR69783B (de)
HU (1)	HU180722B (de)
IE (1)	IE45558B1 (de)
IL (1)	IL52731A0 (de)
MX (1)	MX4740E (de)
NL (1)	NL7709806A (de)
NZ (1)	NZ184932A (de)
PH (1)	PH14771A (de)
PL (1)	PL104309B1 (de)
PT (1)	PT66984B (de)
RO (3)	RO77921A (de)
SE (1)	SE434953B (de)
YU (1)	YU209777A (de)
ZA (1)	ZA774988B (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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 CA CA284,711A patent/CA1082179A/en not_active Expired
- 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
- 1977-08-16 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 PL PL1977200607A patent/PL104309B1/pl not_active IP Right Cessation
- 1977-09-01 AR AR269062A patent/AR226411A1/es active
- 1977-09-01 PT PT66984A patent/PT66984B/pt unknown
- 1977-09-01 DE DE19772739443 patent/DE2739443A1/de active Granted
- 1977-09-02 PH PH20192A patent/PH14771A/en unknown
- 1977-09-02 YU YU02097/77A patent/YU209777A/xx unknown
- 1977-09-02 GB GB36691/77A patent/GB1586709A/en not_active Expired
- 1977-09-06 NL NL7709806A patent/NL7709806A/xx not_active Application Discontinuation
- 1977-09-06 RO RO7798856A patent/RO77921A/ro unknown
- 1977-09-06 RO RO7798857A patent/RO77922A/ro unknown
- 1977-09-06 CH CH1089377A patent/CH631990A5/de not_active IP Right Cessation
- 1977-09-07 FR FR7727080A patent/FR2364220A1/fr active Granted
- 1977-09-07 SE SE7710059A patent/SE434953B/xx not_active IP Right Cessation
- 1977-09-07 AT AT644277A patent/AT360513B/de not_active IP Right Cessation
- 1977-09-07 HU HU77EI762A patent/HU180722B/hu unknown
- 1977-09-07 MX MX776104U patent/MX4740E/es unknown
- 1977-09-07 RO RO7791544A patent/RO72474A/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
- 1977-09-08 DD DD7700200940A patent/DD133055A5/de unknown
- 1977-09-08 ES ES462229A patent/ES462229A1/es not_active Expired
- 1977-09-08 JP JP10834477A patent/JPS5340799A/ja active Granted
1979
- 1979-07-25 AR AR277455A patent/AR230642A1/es active
- 1979-07-25 AR AR277456A patent/AR231643A1/es active

Also Published As

Publication number	Publication date
FR2364220B1 (de)	1980-04-25
PH14771A (en)	1981-12-09
PT66984B (en)	1979-02-13
AU511055B2 (en)	1980-07-24
DE2739443C2 (de)	1991-08-14
PL104309B1 (pl)	1979-08-31
DK146822B (da)	1984-01-16
YU209777A (en)	1982-08-31
SE7710059L (sv)	1978-03-09
AR230642A1 (es)	1984-05-31
ES462229A1 (es)	1978-07-16
RO77921A (ro)	1981-12-25
PL200607A1 (pl)	1978-05-22
NZ184932A (en)	1979-11-01
DE2739443A1 (de)	1978-03-09
NL7709806A (nl)	1978-03-10
SE434953B (sv)	1984-08-27
DK146822C (da)	1984-06-25
RO77922A (ro)	1981-12-25
JPS5340799A (en)	1978-04-13
GR69783B (de)	1982-07-07
DD133055A5 (de)	1978-11-29
ATA644277A (de)	1980-06-15
CA1082179A (en)	1980-07-22
IE771700L (en)	1978-03-08
IL52731A0 (en)	1977-10-31
AR231643A1 (es)	1985-01-31
GB1586709A (en)	1981-03-25
IE45558B1 (en)	1982-09-22
PT66984A (en)	1977-10-01
FR2364220A1 (fr)	1978-04-07
MX4740E (es)	1982-08-25
AU2803977A (en)	1979-02-22
CH631990A5 (en)	1982-09-15
ZA774988B (en)	1979-03-28
RO72474A (ro)	1982-05-10
HU180722B (en)	1983-04-29
DK398577A (da)	1978-03-09
AR226411A1 (es)	1982-07-15
AT360513B (de)	1981-01-12
BE858451A (fr)	1978-03-07

Publication	Publication Date	Title
US4203898A (en)	1980-05-20	Amide derivatives of VLB, leurosidine, leurocristine and related dimeric alkaloids
SU1225490A3 (ru)	1986-04-15	Способ получени производных 0 @ -дезацетилвинка лейкобластин- @ -карбоксигидразида или их солей
JPS5919117B2 (ja)	1984-05-02	ビンブラスチン・ロイロシジンおよびロイロクリスチン誘導体の製法
HU185261B (en)	1984-12-28	Process for preparing n-/vinblastinoyl-23/-derivatives of some aminoacids and peptides
JPS624398B2 (de)	1987-01-30
HU176226B (en)	1981-01-28	Process for producing 4-deacetyl- or 4-deacetoxy-vinblastin-3-carboxamide derivatives
JPS625160B2 (de)	1987-02-03
PL102195B1 (pl)	1979-03-31	A process of producing the new derivative of 6-methylo-8-methylergoline
HU187803B (en)	1986-02-28	Process for producing n-bracket-vinblastinoyl-23-bracket closed-derivatives of amino acids and pharmaceutical compositions containing them
KR810001453B1 (ko)	1981-10-22	인돌-디하이드로인돌 카복스 아마이드 이량체의 제조방법
KR820001240B1 (ko)	1982-07-07	4-데스 아세틸 vlb c-3카복스하이드라지드의 항종양 유도체 제조방법
KR810000494B1 (ko)	1981-05-20	빈카 알카로이드의 옥사졸리딘 디온 유도체의 제조방법
KR790000810B1 (ko)	1979-07-12	빈브라스틴 유도체의 제조방법
KR820001241B1 (ko)	1982-07-07	4-데스아세틸 vlb c-3카복스하이드라지드의 항종양유도체 제조방법
PL120896B1 (en)	1982-03-31	Process for preparing novel derivatives of vinca rosea alkaloids
JPS6153360B2 (de)	1986-11-17
KR810001489B1 (ko)	1981-10-24	빈카 알카로이드의 옥사졸리딘 디온 유도체의 제조방법
KR810001982B1 (ko)	1981-12-08	4-데스아세틸인돌-디하이드로인돌 이량체의 제조방법
KR830002079B1 (ko)	1983-10-11	4'-데옥시 vlb "a"와 "b" 및 관련 1-포르밀 화합물의 3'-산화된 유도체의 제조방법
JPH10120680A (ja)	1998-05-12	新規インドリジン化合物
PL94203B1 (de)	1977-07-30
DK148510B (da)	1985-07-22	Analogifremgangsmaade til fremstilling af derivater af 4-desacetyl-vincaleucoblastin-c-3-carboxhydrazid
HU198074B (en)	1989-07-28	Process for producing new bis-indole derivatives and pharmaceutical compositions comprising these compounds