BG63342B1 - Камптотецинови производни - Google Patents

Камптотецинови производни Download PDF

Info

Publication number: BG63342B1
Authority: BG; Bulgaria
Prior art keywords: group; compound; camptothecin; glycyl; formula
Prior art date: 1995-08-02

Application number

BG100758A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG100758A (bg

Inventor

Kenji Tsujihara

Takayuki Kawaguchi

Satoshi Okuno

Toshiro Yano

Original Assignee

Tanabe Seiyaku Co., Ltd.

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.)

1995-08-02

Filing date

1996-07-31

Publication date

2001-10-31

1996-07-31 Application filed by Tanabe Seiyaku Co., Ltd. filed Critical Tanabe Seiyaku Co., Ltd.

1997-02-28 Publication of BG100758A publication Critical patent/BG100758A/bg

2001-10-31 Publication of BG63342B1 publication Critical patent/BG63342B1/bg

Links

108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 76
150000001413 amino acids Chemical class 0.000 claims abstract description 63
229920001282 polysaccharide Polymers 0.000 claims abstract description 52
239000005017 polysaccharide Substances 0.000 claims abstract description 52
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 51
150000003839 salts Chemical class 0.000 claims abstract description 48
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 20
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
150000004676 glycans Chemical class 0.000 claims abstract 15
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 claims description 181
229940127093 camptothecin Drugs 0.000 claims description 178
150000001875 compounds Chemical class 0.000 claims description 166
-1 hydroxy, mercapto Chemical class 0.000 claims description 141
238000002360 preparation method Methods 0.000 claims description 130
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 86
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 71
239000000203 mixture Substances 0.000 claims description 63
125000003277 amino group Chemical group 0.000 claims description 38
238000006243 chemical reaction Methods 0.000 claims description 32
125000006239 protecting group Chemical group 0.000 claims description 23
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
238000000034 method Methods 0.000 claims description 18
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 8
230000008878 coupling Effects 0.000 claims description 8
238000010168 coupling process Methods 0.000 claims description 8
238000005859 coupling reaction Methods 0.000 claims description 8
206010028980 Neoplasm Diseases 0.000 claims description 6
229920001218 Pullulan Polymers 0.000 claims description 5
239000004373 Pullulan Substances 0.000 claims description 5
210000004899 c-terminal region Anatomy 0.000 claims description 5
235000019423 pullulan Nutrition 0.000 claims description 4
LESXFEZIFXFIQR-ZCFIWIBFSA-N D-Leu-Gly Chemical compound CC(C)C[C@@H]([NH3+])C(=O)NCC([O-])=O LESXFEZIFXFIQR-ZCFIWIBFSA-N 0.000 claims description 3
239000004471 Glycine Substances 0.000 claims description 2
150000002148 esters Chemical class 0.000 claims description 2
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 13
XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Chemical compound NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 claims 8
YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 claims 8
GLUBLISJVJFHQS-SECBINFHSA-N 2-[[(2r)-2-azaniumyl-3-phenylpropanoyl]amino]acetate Chemical compound OC(=O)CNC(=O)[C@H](N)CC1=CC=CC=C1 GLUBLISJVJFHQS-SECBINFHSA-N 0.000 claims 6
239000003085 diluting agent Substances 0.000 claims 6
239000003937 drug carrier Substances 0.000 claims 6
239000008194 pharmaceutical composition Substances 0.000 claims 6
QMOQBVOBWVNSNO-UHFFFAOYSA-N 2-[[2-[[2-[(2-azaniumylacetyl)amino]acetyl]amino]acetyl]amino]acetate Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(O)=O QMOQBVOBWVNSNO-UHFFFAOYSA-N 0.000 claims 4
108010008488 Glycylglycine Proteins 0.000 claims 4
108010067216 glycyl-glycyl-glycine Proteins 0.000 claims 4
108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 claims 4
229940043257 glycylglycine Drugs 0.000 claims 4
229920000180 alkyd Polymers 0.000 claims 2
MXHCPCSDRGLRER-UHFFFAOYSA-N pentaglycine Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(O)=O MXHCPCSDRGLRER-UHFFFAOYSA-N 0.000 claims 2
230000002265 prevention Effects 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 abstract description 13
230000000259 anti-tumor effect Effects 0.000 abstract description 9
230000000694 effects Effects 0.000 abstract description 9
125000002947 alkylene group Chemical group 0.000 abstract description 6
239000003814 drug Substances 0.000 abstract description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 143
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 83
238000001819 mass spectrum Methods 0.000 description 75
239000000843 powder Substances 0.000 description 59
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 52
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
238000005227 gel permeation chromatography Methods 0.000 description 44
229940024606 amino acid Drugs 0.000 description 43
235000001014 amino acid Nutrition 0.000 description 41
238000000354 decomposition reaction Methods 0.000 description 41
150000004804 polysaccharides Chemical class 0.000 description 36
229920002307 Dextran Polymers 0.000 description 35
238000002844 melting Methods 0.000 description 33
230000008018 melting Effects 0.000 description 33
238000004458 analytical method Methods 0.000 description 22
239000011572 manganese Substances 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
238000010521 absorption reaction Methods 0.000 description 18
238000010898 silica gel chromatography Methods 0.000 description 17
238000003756 stirring Methods 0.000 description 16
239000000243 solution Substances 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
238000001914 filtration Methods 0.000 description 12
239000000706 filtrate Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
229910052739 hydrogen Inorganic materials 0.000 description 10
239000011734 sodium Substances 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
238000006467 substitution reaction Methods 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
238000001816 cooling Methods 0.000 description 7
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 7
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
239000004375 Dextrin Substances 0.000 description 6
229920001353 Dextrin Polymers 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
230000000052 comparative effect Effects 0.000 description 6
235000019425 dextrin Nutrition 0.000 description 6
150000002576 ketones Chemical class 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
239000002246 antineoplastic agent Substances 0.000 description 5
125000004181 carboxyalkyl group Chemical group 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
102000004196 processed proteins & peptides Human genes 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000010531 catalytic reduction reaction Methods 0.000 description 4
238000006482 condensation reaction Methods 0.000 description 4
229960003692 gamma aminobutyric acid Drugs 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
125000006501 nitrophenyl group Chemical group 0.000 description 4
239000003921 oil Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
UAHPMMRIRFRGJP-UHFFFAOYSA-N 1-[5-(3-hydroxypropoxy)-2-nitrophenyl]prop-2-en-1-one Chemical compound OCCCOC1=CC=C([N+]([O-])=O)C(C(=O)C=C)=C1 UAHPMMRIRFRGJP-UHFFFAOYSA-N 0.000 description 3
AERPLYFHHMHCQN-UHFFFAOYSA-N 3-(1-hydroxyprop-2-enyl)-4-nitrophenol Chemical compound C=CC(O)C1=CC(O)=CC=C1[N+]([O-])=O AERPLYFHHMHCQN-UHFFFAOYSA-N 0.000 description 3
KLKKIENVIGQBAG-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCNC(=O)OC(C)(C)C)C=C1 KLKKIENVIGQBAG-UHFFFAOYSA-N 0.000 description 3
AHSDEILNPHUJGK-UHFFFAOYSA-N 5-[3-[tert-butyl(dimethyl)silyl]oxypropoxy]-2-nitrobenzaldehyde Chemical compound CC(C)(C)[Si](C)(C)OCCCOC1=CC=C([N+]([O-])=O)C(C=O)=C1 AHSDEILNPHUJGK-UHFFFAOYSA-N 0.000 description 3
229920002101 Chitin Polymers 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
229940079593 drug Drugs 0.000 description 3
125000002768 hydroxyalkyl group Chemical group 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
230000007935 neutral effect Effects 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 3
OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
YUNMDKMTHSECEM-UHFFFAOYSA-N 1-[5-[2-[tert-butyl(dimethyl)silyl]oxyethoxy]-2-nitrophenyl]prop-2-en-1-one Chemical compound CC(C)(C)[Si](C)(C)OCCOC1=CC=C([N+]([O-])=O)C(C(=O)C=C)=C1 YUNMDKMTHSECEM-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
239000007818 Grignard reagent Substances 0.000 description 2
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
239000004472 Lysine Substances 0.000 description 2
208000005718 Stomach Neoplasms Diseases 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000002431 aminoalkoxy group Chemical group 0.000 description 2
UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000012377 drug delivery Methods 0.000 description 2
239000000428 dust Substances 0.000 description 2
206010017758 gastric cancer Diseases 0.000 description 2
150000004795 grignard reagents Chemical class 0.000 description 2
229920000669 heparin Polymers 0.000 description 2
229960002897 heparin Drugs 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 2
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
201000011549 stomach cancer Diseases 0.000 description 2
QSQIGNHVIQNSTQ-UHFFFAOYSA-N tert-butyl n-[3-(4-nitro-3-prop-2-enoylphenoxy)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCOC1=CC=C([N+]([O-])=O)C(C(=O)C=C)=C1 QSQIGNHVIQNSTQ-UHFFFAOYSA-N 0.000 description 2
VFPATNYFVLEJLW-UHFFFAOYSA-N tert-butyl n-[3-[3-(1-hydroxyprop-2-enyl)-4-nitrophenoxy]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCOC1=CC=C([N+]([O-])=O)C(C(O)C=C)=C1 VFPATNYFVLEJLW-UHFFFAOYSA-N 0.000 description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000004448 titration Methods 0.000 description 2
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
- C07K9/001—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence having less than 12 amino acids and not being part of a ring structure
- C07K9/003—Peptides being substituted by heterocyclic radicals, e.g. bleomycin, phleomycin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

BG100758A 1995-08-02 1996-07-31 Камптотецинови производни BG63342B1 (bg)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
JP19739195		1995-08-02
JP34061995		1995-12-27
JP17337296		1996-07-03

Publications (2)

Publication Number	Publication Date
BG100758A BG100758A (bg)	1997-02-28
BG63342B1 true BG63342B1 (bg)	2001-10-31

Family

ID=27323772

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG100758A BG63342B1 (bg)	1995-08-02	1996-07-31	Камптотецинови производни

Country Status (19)

Country	Link
US (1)	US5837673A (fr)
EP (1)	EP0757049B1 (fr)
KR (1)	KR100387191B1 (fr)
CN (2)	CN1143859C (fr)
AT (1)	ATE178067T1 (fr)
AU (1)	AU717653B2 (fr)
BG (1)	BG63342B1 (fr)
CA (1)	CA2182244C (fr)
DE (1)	DE69601841T2 (fr)
DK (1)	DK0757049T3 (fr)
ES (1)	ES2131913T3 (fr)
GR (1)	GR3029796T3 (fr)
HU (1)	HUP9602122A3 (fr)
IL (1)	IL118957A (fr)
MY (1)	MY116665A (fr)
NO (1)	NO315469B1 (fr)
RU (1)	RU2138503C1 (fr)
SG (1)	SG50747A1 (fr)
TW (1)	TW466242B (fr)

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PT3088419T (pt)	2013-12-25	2019-01-11	Daiichi Sankyo Co Ltd	Conjugado de anticorpo anti-trop2-fármaco
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ES2754348T3 (es)	2014-04-10	2020-04-17	Daiichi Sankyo Co Ltd	Conjugado de (anticuerpo anti-HER2)-fármaco
CN111228511B (zh)	2014-04-10	2024-06-18	第一三共株式会社	抗her3抗体-药物偶联物
CN116059395A (zh)	2015-06-29	2023-05-05	第一三共株式会社	用于选择性制造抗体-药物缀合物的方法
EP3552626A4 (fr)	2016-12-12	2020-06-10	Daiichi Sankyo Company, Limited	Association d'un conjugué anticorps-médicament et d'un inhibiteur de point de contrôle immunitaire
EP3572428A4 (fr)	2017-01-17	2020-12-30	Daiichi Sankyo Company, Limited	Anticorps anti-gpr20 et conjugué anticorps-médicament anti-gpr20
CA3059527A1 (fr)	2017-04-14	2018-10-18	Capsugel Belgium Nv	Capsules de pullulane
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TWI855528B (zh)	2017-05-15	2024-09-11	日商第一三共股份有限公司	抗體-藥物結合物之製造方法
JP7248578B2 (ja)	2017-08-31	2023-03-29	第一三共株式会社	抗体－薬物コンジュゲートの新規製造方法
KR20250084239A (ko)	2017-08-31	2025-06-10	다이이찌 산쿄 가부시키가이샤	항체-약물 콘주게이트의 개량 제조 방법
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1996
- 1996-07-24 SG SG1996010359A patent/SG50747A1/en unknown
- 1996-07-25 AU AU60698/96A patent/AU717653B2/en not_active Ceased
- 1996-07-25 IL IL11895796A patent/IL118957A/xx not_active IP Right Cessation
- 1996-07-29 CA CA002182244A patent/CA2182244C/fr not_active Expired - Fee Related
- 1996-07-30 US US08/689,018 patent/US5837673A/en not_active Expired - Lifetime
- 1996-07-30 DK DK96305579T patent/DK0757049T3/da active
- 1996-07-30 AT AT96305579T patent/ATE178067T1/de not_active IP Right Cessation
- 1996-07-30 DE DE69601841T patent/DE69601841T2/de not_active Expired - Fee Related
- 1996-07-30 EP EP96305579A patent/EP0757049B1/fr not_active Expired - Lifetime
- 1996-07-30 ES ES96305579T patent/ES2131913T3/es not_active Expired - Lifetime
- 1996-07-31 BG BG100758A patent/BG63342B1/bg unknown
- 1996-08-01 MY MYPI96003153A patent/MY116665A/en unknown
- 1996-08-01 RU RU96115394A patent/RU2138503C1/ru not_active IP Right Cessation
- 1996-08-01 NO NO19963214A patent/NO315469B1/no not_active IP Right Cessation
- 1996-08-01 HU HU9602122A patent/HUP9602122A3/hu unknown
- 1996-08-02 KR KR1019960032296A patent/KR100387191B1/ko not_active Expired - Fee Related
- 1996-08-02 CN CNB001326619A patent/CN1143859C/zh not_active Expired - Fee Related
- 1996-08-02 TW TW085109331A patent/TW466242B/zh not_active IP Right Cessation
- 1996-08-02 CN CN96106979A patent/CN1075501C/zh not_active Expired - Fee Related
1999
- 1999-03-26 GR GR990400802T patent/GR3029796T3/el unknown

Also Published As

Publication number	Publication date
DK0757049T3 (da)	1999-06-23
TW466242B (en)	2001-12-01
HUP9602122A3 (en)	1998-07-28
CN1145365A (zh)	1997-03-19
KR19980013708A (ko)	1998-05-15
CA2182244C (fr)	2004-02-03
EP0757049B1 (fr)	1999-03-24
US5837673A (en)	1998-11-17
AU6069896A (en)	1997-02-06
NO963214D0 (no)	1996-08-01
IL118957A0 (en)	1996-10-31
CN1308078A (zh)	2001-08-15
EP0757049A1 (fr)	1997-02-05
HUP9602122A2 (en)	1997-11-28
RU2138503C1 (ru)	1999-09-27
IL118957A (en)	2000-11-21
HK1005545A1 (en)	1999-01-15
MY116665A (en)	2004-03-31
KR100387191B1 (ko)	2003-10-04
DE69601841T2 (de)	1999-08-05
SG50747A1 (en)	1998-07-20
CN1143859C (zh)	2004-03-31
CA2182244A1 (fr)	1997-02-03
AU717653B2 (en)	2000-03-30
HU9602122D0 (en)	1996-09-30
NO963214L (no)	1997-02-03
NO315469B1 (no)	2003-09-08
GR3029796T3 (en)	1999-06-30
DE69601841D1 (de)	1999-04-29
CN1075501C (zh)	2001-11-28
BG100758A (bg)	1997-02-28
ATE178067T1 (de)	1999-04-15
ES2131913T3 (es)	1999-08-01

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