JPH08509740A - カンプトテシンの水溶性誘導体 - Google Patents

カンプトテシンの水溶性誘導体

Info

Publication number: JPH08509740A
Authority: JP; Japan
Prior art keywords: lower alkyl; camptothecin; compound; formula; ethylenedioxy
Prior art date: 1993-04-29
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.): Pending

Application number

JP6524540A

Other languages

English (en)

Japanese (ja)

Inventor

マークベスタマン，ジェフリー

グレンエバレズ，マイケル

ヨセフルッツィオ，ミカエル

レスリーマイアズ，ピーター

Original Assignee

グラクソ、ウェルカム、インコーポレーテッド

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.)

1993-04-29

Filing date

1994-04-28

Publication date

1996-10-15

1994-04-28 Application filed by グラクソ、ウェルカム、インコーポレーテッド filed Critical グラクソ、ウェルカム、インコーポレーテッド

1996-10-15 Publication of JPH08509740A publication Critical patent/JPH08509740A/ja

Status Pending legal-status Critical Current

Links

VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 title abstract description 20
-1 N-methylpyrrolyl Chemical group 0.000 claims abstract description 90
125000000217 alkyl group Chemical group 0.000 claims abstract description 58
150000003839 salts Chemical class 0.000 claims abstract description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 28
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 24
125000004076 pyridyl group Chemical group 0.000 claims abstract description 20
125000002883 imidazolyl group Chemical group 0.000 claims abstract description 19
125000002541 furyl group Chemical group 0.000 claims abstract description 18
229910052736 halogen Inorganic materials 0.000 claims abstract description 17
150000002367 halogens Chemical class 0.000 claims abstract description 17
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
239000001257 hydrogen Substances 0.000 claims abstract description 17
206010028980 Neoplasm Diseases 0.000 claims abstract description 15
239000012453 solvate Substances 0.000 claims abstract description 15
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
125000001424 substituent group Chemical group 0.000 claims abstract description 12
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 11
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
238000004519 manufacturing process Methods 0.000 claims abstract description 7
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
150000001875 compounds Chemical class 0.000 claims description 134
238000000034 method Methods 0.000 claims description 31
238000006243 chemical reaction Methods 0.000 claims description 26
239000002253 acid Substances 0.000 claims description 19
VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 14
150000002431 hydrogen Chemical class 0.000 claims description 11
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
102000003915 DNA Topoisomerases Human genes 0.000 claims description 7
108090000323 DNA Topoisomerases Proteins 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 7
230000000259 anti-tumor effect Effects 0.000 claims description 7
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
230000002401 inhibitory effect Effects 0.000 claims description 5
YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 3
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
102000004190 Enzymes Human genes 0.000 claims description 2
108090000790 Enzymes Proteins 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
239000001301 oxygen Substances 0.000 claims 1
229910052760 oxygen Inorganic materials 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 3
239000000203 mixture Substances 0.000 description 26
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
238000001819 mass spectrum Methods 0.000 description 18
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
239000002904 solvent Substances 0.000 description 13
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 12
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
229940127093 camptothecin Drugs 0.000 description 11
238000000354 decomposition reaction Methods 0.000 description 11
238000009472 formulation Methods 0.000 description 11
239000007787 solid Substances 0.000 description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000004615 ingredient Substances 0.000 description 9
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
239000000047 product Substances 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
235000009518 sodium iodide Nutrition 0.000 description 6
239000000243 solution Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000000126 substance Substances 0.000 description 6
238000005160 1H NMR spectroscopy Methods 0.000 description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
229940093956 potassium carbonate Drugs 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
101710183280 Topoisomerase Proteins 0.000 description 4
239000002246 antineoplastic agent Substances 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
239000012458 free base Substances 0.000 description 4
150000002596 lactones Chemical group 0.000 description 4
239000003921 oil Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000000967 suction filtration Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
AGJAUFUNZWHLKE-UHFFFAOYSA-N (2E,4E)-N-isobutyl-2,4-tetradecadienamide Natural products CCCCCCCCCC=CC=CC(=O)NCC(C)C AGJAUFUNZWHLKE-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
125000003710 aryl alkyl group Chemical group 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
239000002775 capsule Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
230000008034 disappearance Effects 0.000 description 3
238000010828 elution Methods 0.000 description 3
239000008187 granular material Substances 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
239000010410 layer Substances 0.000 description 3
208000032839 leukemia Diseases 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
239000002609 medium Substances 0.000 description 3
238000000465 moulding Methods 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000009467 reduction Effects 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
238000004007 reversed phase HPLC Methods 0.000 description 3
239000002002 slurry Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
239000003826 tablet Substances 0.000 description 3
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
239000005977 Ethylene Substances 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
208000025865 Ulcer Diseases 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
238000010171 animal model Methods 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
229940127089 cytotoxic agent Drugs 0.000 description 2
230000001472 cytotoxic effect Effects 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
229940079593 drug Drugs 0.000 description 2
235000019439 ethyl acetate Nutrition 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
230000012010 growth Effects 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000001630 malic acid Substances 0.000 description 2
235000011090 malic acid Nutrition 0.000 description 2
239000012528 membrane Substances 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 2
229940050176 methyl chloride Drugs 0.000 description 2
239000011707 mineral Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
239000012454 non-polar solvent Substances 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000003880 polar aprotic solvent Substances 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
229920000728 polyester Polymers 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
210000003491 skin Anatomy 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
229940001593 sodium carbonate Drugs 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000002562 thickening agent Substances 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
231100000397 ulcer Toxicity 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
BZKOZYWGZKRTIB-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-amine Chemical compound O1CCOC2=CC(N)=CC=C21 BZKOZYWGZKRTIB-UHFFFAOYSA-N 0.000 description 1
MEVXSUZBFYZPHZ-UHFFFAOYSA-N 2-amino-3-methyl-4h-imidazol-5-one;sulfuric acid Chemical compound OS(O)(=O)=O.CN1CC(=O)N=C1N MEVXSUZBFYZPHZ-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (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 Condensed Heterocyclic Rings (AREA)
Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)

JP6524540A 1993-04-29 1994-04-28 カンプトテシンの水溶性誘導体 Pending JPH08509740A (ja)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US5458593A	1993-04-29	1993-04-29
US8104293A	1993-06-22	1993-06-22
US08/081,042		1993-06-22
US08/054,585		1993-06-22
PCT/US1994/004681 WO1994025466A1 (fr)	1993-04-29	1994-04-28	Derives hydrosolubles de camptothecine et leur utilisation comme agents antitumoraux

Publications (1)

Publication Number	Publication Date
JPH08509740A true JPH08509740A (ja)	1996-10-15

Family

ID=26733234

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP6524540A Pending JPH08509740A (ja)	1993-04-29	1994-04-28	カンプトテシンの水溶性誘導体

Country Status (10)

Country	Link
EP (1)	EP0696285A1 (fr)
JP (1)	JPH08509740A (fr)
AP (1)	AP9400638A0 (fr)
AU (1)	AU6777194A (fr)
CA (1)	CA2161681A1 (fr)
IL (1)	IL109470A0 (fr)
IS (1)	IS4152A (fr)
MY (1)	MY141374A (fr)
PE (1)	PE52894A1 (fr)
WO (1)	WO1994025466A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2003519234A (ja) *	1999-12-29	2003-06-17	リサーチ・トライアングル・インスティチュート	トポイソメラーゼＩ阻害を有するカンプトテシンβ−アラニンエステル

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6504029B1 (en) *	1995-04-10	2003-01-07	Daiichi Pharmaceutical Co., Ltd.	Condensed-hexacyclic compounds and a process therefor
US5663177A (en) *	1995-05-31	1997-09-02	Smithkline Beecham Corporation	Water soluble camptothecin analogs
SG103322A1 (en) *	1996-10-30	2004-04-29	Tanabe Seiyaku Co	S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds and process for preparation thereof
US6559309B2 (en)	1996-11-01	2003-05-06	Osi Pharmaceuticals, Inc.	Preparation of a camptothecin derivative by intramolecular cyclisation
US6046209A (en) *	1997-05-27	2000-04-04	Smithkline Beecham Corporation	Water soluble camptothecin analogs
IN189180B (fr) *	1997-07-09	2003-01-04	Chong Kun Dang Corp
US6833373B1 (en)	1998-12-23	2004-12-21	G.D. Searle & Co.	Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia
US6858598B1 (en)	1998-12-23	2005-02-22	G. D. Searle & Co.	Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK0418099T3 (da) *	1989-09-15	2002-04-02	Res Triangle Inst	Fremgangsmåde til fremstilling af 10,11-methylendioxy-20(RS)-camptothecin og 10,11-methylendioxy-20(S)-camptothecinanaloger
EP0540099B1 (fr) *	1991-10-29	1996-04-17	Glaxo Wellcome Inc.	Dérivés de camptothécine solubles dans l'eau
CA2087898A1 (fr) *	1992-01-24	1993-07-25	Hiroshi Akimoto	Composes heterocycliques condenses, leur preparation et leur utilisation

1994
- 1994-04-25 IS IS4152A patent/IS4152A/is unknown
- 1994-04-27 MY MYPI94001039A patent/MY141374A/en unknown
- 1994-04-27 PE PE1994241061A patent/PE52894A1/es not_active Application Discontinuation
- 1994-04-28 WO PCT/US1994/004681 patent/WO1994025466A1/fr not_active Ceased
- 1994-04-28 AU AU67771/94A patent/AU6777194A/en not_active Abandoned
- 1994-04-28 EP EP94915931A patent/EP0696285A1/fr not_active Withdrawn
- 1994-04-28 IL IL10947094A patent/IL109470A0/xx unknown
- 1994-04-28 AP APAP/P/1994/000638A patent/AP9400638A0/en unknown
- 1994-04-28 CA CA002161681A patent/CA2161681A1/fr not_active Abandoned
- 1994-04-28 JP JP6524540A patent/JPH08509740A/ja active Pending

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2003519234A (ja) *	1999-12-29	2003-06-17	リサーチ・トライアングル・インスティチュート	トポイソメラーゼＩ阻害を有するカンプトテシンβ−アラニンエステル

Also Published As

Publication number	Publication date
IS4152A (is)	1994-10-30
PE52894A1 (es)	1995-01-06
EP0696285A1 (fr)	1996-02-14
CA2161681A1 (fr)	1994-11-10
AU6777194A (en)	1994-11-21
WO1994025466A1 (fr)	1994-11-10
IL109470A0 (en)	1994-07-31
AP9400638A0 (en)	1995-10-28
MY141374A (en)	2010-04-16

Publication	Publication Date	Title
JP3020760B2 (ja)	2000-03-15	水溶性カンプトテシン誘導体
US5559235A (en)	1996-09-24	Water soluble camptothecin derivatives
US5342947A (en)	1994-08-30	Preparation of water soluble camptothecin derivatives
AU652728B2 (en)	1994-09-08	Camptothecin analogs as potent inhibitors of human colorectal cancer
US6100273A (en)	2000-08-08	Water soluble camptothecin derivatives
US4981968A (en)	1991-01-01	Synthesis of camptothecin and analogs thereof
US5122526A (en)	1992-06-16	Camptothecin and analogs thereof and pharmaceutical compositions and method using them
US5401747A (en)	1995-03-28	Alkyl camptothecin compounds as potent inhibitors of human colorectal cancer
WO1992021661A1 (fr)	1992-12-10	Composes cycliques antitumoraux
JPH10503525A (ja)	1998-03-31	カンプトテシン誘導体及びその製造方法
US5227380A (en)	1993-07-13	Pharmaceutical compositions and methods employing camptothecins
JPH08509740A (ja)	1996-10-15	カンプトテシンの水溶性誘導体
RU2450007C2 (ru)	2012-05-10	Производные камптотецина с противоопухолевой активностью
CN115340526B (zh)	2024-02-02	邻二甲酰亚胺类化合物及其药物组合物、制备方法和用途
JP5198447B2 (ja)	2013-05-15	抗腫瘍活性を有するカンプトテシン誘導体
GB2280674A (en)	1995-02-08	Pyrido[3,4-b]-pyridine antitumor compounds
SI9300183A (sl)	1994-12-31	Vodotopni kamptotecinski derivati
JPH0834788A (ja)	1996-02-06	ピロロベンゾカルバゾール誘導体及びその製造方法
JPH08283271A (ja)	1996-10-29	インドロカルバゾール誘導体
JPH0834787A (ja)	1996-02-06	ピロロカルバゾール誘導体及びその製造方法

JPH08509740A - カンプトテシンの水溶性誘導体 - Google Patents

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Applications Claiming Priority (5)

Publications (1)

Family

ID=26733234

Family Applications (1)

Country Status (10)

Cited By (1)

Families Citing this family (8)

Family Cites Families (3)

Cited By (1)

Also Published As

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