IL88517A - Water soluble camptothecin analogs, their preparation, pharmaceutical compositions containing them, some intermediates thereof and their preparation - Google Patents

Water soluble camptothecin analogs, their preparation, pharmaceutical compositions containing them, some intermediates thereof and their preparation

Info

Publication number: IL88517A
Authority: IL; Israel
Prior art keywords: compound; hydroxy; hydrogen; formyl; formula
Prior art date: 1987-12-01

Application number

IL8851788A

Other languages

English (en)

Other versions

IL88517A0 (en

Original Assignee

Smithkline Beckman Corp

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.)

1987-12-01

Filing date

1988-11-28

Publication date

1994-10-07

1988-11-28 Application filed by Smithkline Beckman Corp filed Critical Smithkline Beckman Corp

1989-06-30 Publication of IL88517A0 publication Critical patent/IL88517A0/xx

1994-10-07 Publication of IL88517A publication Critical patent/IL88517A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
238000002360 preparation method Methods 0.000 title abstract description 8
239000000543 intermediate Substances 0.000 title abstract description 3
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 description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 189
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 42
-1 -CH2NH2 Chemical group 0.000 claims abstract description 40
239000001257 hydrogen Chemical group 0.000 claims abstract description 32
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 18
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 16
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
238000000034 method Methods 0.000 claims abstract description 13
125000000217 alkyl group Chemical group 0.000 claims abstract description 10
230000008569 process Effects 0.000 claims abstract description 10
125000002837 carbocyclic group Chemical group 0.000 claims abstract description 6
230000004565 tumor cell growth Effects 0.000 claims abstract description 6
125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 5
125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 5
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
239000012453 solvate Substances 0.000 claims abstract description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 4
XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical group N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims abstract 3
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 42
HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 claims description 21
HAWSQZCWOQZXHI-UHFFFAOYSA-N CPT-OH Natural products C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-UHFFFAOYSA-N 0.000 claims description 21
241001465754 Metazoa Species 0.000 claims description 15
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 14
230000002401 inhibitory effect Effects 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 14
210000004881 tumor cell Anatomy 0.000 claims description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
229910052757 nitrogen Inorganic materials 0.000 claims description 7
159000000000 sodium salts Chemical class 0.000 claims description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 5
150000001450 anions Chemical class 0.000 claims description 5
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
159000000021 acetate salts Chemical class 0.000 claims description 4
238000009833 condensation Methods 0.000 claims description 4
230000005494 condensation Effects 0.000 claims description 4
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 4
230000012010 growth Effects 0.000 claims description 4
150000002431 hydrogen Chemical group 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 3
238000010438 heat treatment Methods 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
239000012442 inert solvent Substances 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
238000006722 reduction reaction Methods 0.000 claims description 3
150000003573 thiols Chemical class 0.000 claims description 3
239000002168 alkylating agent Substances 0.000 claims description 2
229940100198 alkylating agent Drugs 0.000 claims description 2
230000006315 carbonylation Effects 0.000 claims description 2
238000005810 carbonylation reaction Methods 0.000 claims description 2
238000010531 catalytic reduction reaction Methods 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
230000009467 reduction Effects 0.000 claims description 2
150000003335 secondary amines Chemical class 0.000 claims description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims 3
238000004519 manufacturing process Methods 0.000 claims 2
239000003153 chemical reaction reagent Substances 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
230000022244 formylation Effects 0.000 claims 1
238000006170 formylation reaction Methods 0.000 claims 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims 1
239000006201 parenteral dosage form Substances 0.000 claims 1
150000003141 primary amines Chemical class 0.000 claims 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims 1
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims 1
239000003112 inhibitor Substances 0.000 abstract description 3
125000006528 (C2-C6) alkyl group Chemical group 0.000 abstract 1
238000002560 therapeutic procedure Methods 0.000 abstract 1
206010028980 Neoplasm Diseases 0.000 description 137
230000000694 effects Effects 0.000 description 52
208000032839 leukemia Diseases 0.000 description 41
239000003814 drug Substances 0.000 description 32
229940079593 drug Drugs 0.000 description 32
241000699670 Mus sp. Species 0.000 description 31
210000004027 cell Anatomy 0.000 description 27
208000001382 Experimental Melanoma Diseases 0.000 description 26
238000011282 treatment Methods 0.000 description 25
230000005764 inhibitory process Effects 0.000 description 23
230000004614 tumor growth Effects 0.000 description 22
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 21
229940127093 camptothecin Drugs 0.000 description 21
208000029742 colonic neoplasm Diseases 0.000 description 19
238000002474 experimental method Methods 0.000 description 17
208000006552 Lewis Lung Carcinoma Diseases 0.000 description 15
206010009944 Colon cancer Diseases 0.000 description 14
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 14
206010039491 Sarcoma Diseases 0.000 description 14
206010061289 metastatic neoplasm Diseases 0.000 description 11
231100000331 toxic Toxicity 0.000 description 11
230000002588 toxic effect Effects 0.000 description 11
201000010897 colon adenocarcinoma Diseases 0.000 description 10
230000007774 longterm Effects 0.000 description 10
230000001394 metastastic effect Effects 0.000 description 10
206010058467 Lung neoplasm malignant Diseases 0.000 description 9
238000001727 in vivo Methods 0.000 description 9
239000002246 antineoplastic agent Substances 0.000 description 8
229940041181 antineoplastic drug Drugs 0.000 description 8
201000005296 lung carcinoma Diseases 0.000 description 8
108020004414 DNA Proteins 0.000 description 7
102000003915 DNA Topoisomerases Human genes 0.000 description 7
108090000323 DNA Topoisomerases Proteins 0.000 description 7
230000000259 anti-tumor effect Effects 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
229960004679 doxorubicin Drugs 0.000 description 7
230000004083 survival effect Effects 0.000 description 7
241000283984 Rodentia Species 0.000 description 6
230000001472 cytotoxic effect Effects 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
238000006683 Mannich reaction Methods 0.000 description 5
239000002253 acid Substances 0.000 description 5
238000010367 cloning Methods 0.000 description 5
231100000433 cytotoxic Toxicity 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
238000002513 implantation Methods 0.000 description 5
229930014626 natural product Natural products 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
102000007537 Type II DNA Topoisomerases Human genes 0.000 description 4
108010046308 Type II DNA Topoisomerases Proteins 0.000 description 4
201000008274 breast adenocarcinoma Diseases 0.000 description 4
239000000039 congener Substances 0.000 description 4
230000003013 cytotoxicity Effects 0.000 description 4
231100000135 cytotoxicity Toxicity 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
208000020816 lung neoplasm Diseases 0.000 description 4
208000037841 lung tumor Diseases 0.000 description 4
101150077795 mdr gene Proteins 0.000 description 4
KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 4
229960001156 mitoxantrone Drugs 0.000 description 4
230000036457 multidrug resistance Effects 0.000 description 4
230000003389 potentiating effect Effects 0.000 description 4
230000002035 prolonged effect Effects 0.000 description 4
230000035945 sensitivity Effects 0.000 description 4
238000001228 spectrum Methods 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
206010006187 Breast cancer Diseases 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
208000007452 Plasmacytoma Diseases 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
210000003527 eukaryotic cell Anatomy 0.000 description 3
239000002609 medium Substances 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
229920001817 Agar Polymers 0.000 description 2
238000012935 Averaging Methods 0.000 description 2
208000026310 Breast neoplasm Diseases 0.000 description 2
238000006364 Duff aldehyde synthesis reaction Methods 0.000 description 2
241000196324 Embryophyta Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
241001529936 Murinae Species 0.000 description 2
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
206010034133 Pathogen resistance Diseases 0.000 description 2
239000008272 agar Substances 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229930013930 alkaloid Natural products 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
150000001721 carbon Chemical group 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
238000001647 drug administration Methods 0.000 description 2
CTSPAMFJBXKSOY-UHFFFAOYSA-N ellipticine Chemical compound N1=CC=C2C(C)=C(NC=3C4=CC=CC=3)C4=C(C)C2=C1 CTSPAMFJBXKSOY-UHFFFAOYSA-N 0.000 description 2
210000000981 epithelium Anatomy 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
150000002596 lactones Chemical class 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000000174 oncolytic effect Effects 0.000 description 2
238000011369 optimal treatment Methods 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
230000000306 recurrent effect Effects 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
230000004043 responsiveness Effects 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000000243 solution Substances 0.000 description 2
241000894007 species Species 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
238000004114 suspension culture Methods 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
238000006257 total synthesis reaction Methods 0.000 description 2
238000013518 transcription Methods 0.000 description 2
230000035897 transcription Effects 0.000 description 2
238000011269 treatment regimen Methods 0.000 description 2
208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
208000036832 Adenocarcinoma of ovary Diseases 0.000 description 1
241000234282 Allium Species 0.000 description 1
235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
241000922351 Anoma Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
238000011735 C3H mouse Methods 0.000 description 1
241000759909 Camptotheca Species 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
108010077544 Chromatin Proteins 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
102000053602 DNA Human genes 0.000 description 1
230000004543 DNA replication Effects 0.000 description 1
229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
ZIXGXMMUKPLXBB-UHFFFAOYSA-N Guatambuinine Natural products N1C2=CC=CC=C2C2=C1C(C)=C1C=CN=C(C)C1=C2 ZIXGXMMUKPLXBB-UHFFFAOYSA-N 0.000 description 1
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 1
208000005045 Interdigitating dendritic cell sarcoma Diseases 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
102000012750 Membrane Glycoproteins Human genes 0.000 description 1
108010090054 Membrane Glycoproteins Proteins 0.000 description 1
206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
208000034578 Multiple myelomas Diseases 0.000 description 1
101100180399 Mus musculus Izumo1r gene Proteins 0.000 description 1
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
241000060390 Nothapodytes nimmoniana Species 0.000 description 1
206010061328 Ovarian epithelial cancer Diseases 0.000 description 1
206010035226 Plasma cell myeloma Diseases 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
SUYXJDLXGFPMCQ-INIZCTEOSA-N SJ000287331 Natural products CC1=c2cnccc2=C(C)C2=Nc3ccccc3[C@H]12 SUYXJDLXGFPMCQ-INIZCTEOSA-N 0.000 description 1
101710183280 Topoisomerase Proteins 0.000 description 1
239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
ZEEBGORNQSEQBE-UHFFFAOYSA-N [2-(3-phenylphenoxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound C1(=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)C1=CC=CC=C1 ZEEBGORNQSEQBE-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000003797 alkaloid derivatives Chemical class 0.000 description 1
230000003321 amplification Effects 0.000 description 1
XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
229960001220 amsacrine Drugs 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
201000008275 breast carcinoma Diseases 0.000 description 1
239000012830 cancer therapeutic Substances 0.000 description 1
150000007942 carboxylates Chemical group 0.000 description 1
230000003915 cell function Effects 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000033077 cellular process Effects 0.000 description 1
150000001793 charged compounds Chemical group 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
210000003483 chromatin Anatomy 0.000 description 1
230000002759 chromosomal effect Effects 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
238000012398 clinical drug development Methods 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
230000001461 cytolytic effect Effects 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
239000002254 cytotoxic agent Substances 0.000 description 1
231100000599 cytotoxic agent Toxicity 0.000 description 1
238000011161 development Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
231100000371 dose-limiting toxicity Toxicity 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
230000029142 excretion Effects 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
238000009093 first-line therapy Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 1
230000005917 in vivo anti-tumor Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
210000002490 intestinal epithelial cell Anatomy 0.000 description 1
210000001985 kidney epithelial cell Anatomy 0.000 description 1
230000002147 killing effect Effects 0.000 description 1
ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
208000021039 metastatic melanoma Diseases 0.000 description 1
208000037843 metastatic solid tumor Diseases 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
238000004264 monolayer culture Methods 0.000 description 1
VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
230000000683 nonmetastatic effect Effects 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
208000013371 ovarian adenocarcinoma Diseases 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
201000006588 ovary adenocarcinoma Diseases 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
208000028591 pheochromocytoma Diseases 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000005588 protonation Effects 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
230000010076 replication Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
208000029922 reticulum cell sarcoma Diseases 0.000 description 1
238000012552 review Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
238000011519 second-line treatment Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000005783 single-strand break Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000001839 systemic circulation Effects 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
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 1
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 1
229960004528 vincristine Drugs 0.000 description 1
235000020138 yakult Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Steroid Compounds (AREA)
Semiconductor Lasers (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

IL8851788A 1987-12-01 1988-11-28 Water soluble camptothecin analogs, their preparation, pharmaceutical compositions containing them, some intermediates thereof and their preparation IL88517A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US12714887A	1987-12-01	1987-12-01

Publications (2)

Publication Number	Publication Date
IL88517A0 IL88517A0 (en)	1989-06-30
IL88517A true IL88517A (en)	1994-10-07

Family

ID=22428545

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL8851788A IL88517A (en)	1987-12-01	1988-11-28	Water soluble camptothecin analogs, their preparation, pharmaceutical compositions containing them, some intermediates thereof and their preparation

Country Status (25)

Country	Link
US (1)	US5004758A (fr)
EP (1)	EP0321122B1 (fr)
JP (1)	JPH0633268B2 (fr)
KR (1)	KR930009357B1 (fr)
CN (3)	CN1027265C (fr)
AT (1)	ATE143368T1 (fr)
AU (1)	AU612735B2 (fr)
CA (1)	CA1308102C (fr)
CY (1)	CY2017A (fr)
DE (2)	DE3855575T2 (fr)
DK (1)	DK173034B1 (fr)
ES (1)	ES2094721T3 (fr)
FI (1)	FI89923C (fr)
GR (1)	GR3021990T3 (fr)
HK (1)	HK81097A (fr)
IE (1)	IE74873B1 (fr)
IL (1)	IL88517A (fr)
LU (2)	LU90026I2 (fr)
MX (1)	MX9203744A (fr)
NL (1)	NL970017I2 (fr)
NO (2)	NO170487C (fr)
NZ (1)	NZ227124A (fr)
PT (1)	PT89111B (fr)
SG (1)	SG66254A1 (fr)
ZA (1)	ZA888938B (fr)

Families Citing this family (143)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5227380A (en) *	1987-03-31	1993-07-13	Research Triangle Institute	Pharmaceutical compositions and methods employing camptothecins
US5053512A (en) *	1987-04-14	1991-10-01	Research Triangle Institute	Total synthesis of 20(S) and 20(R)-camptothecin and compthothecin derivatives
US5106742A (en) *	1987-03-31	1992-04-21	Wall Monroe E	Camptothecin analogs as potent inhibitors of topoisomerase I
US5122526A (en) *	1987-03-31	1992-06-16	Research Triangle Institute	Camptothecin and analogs thereof and pharmaceutical compositions and method using them
US5364858A (en) *	1987-03-31	1994-11-15	Research Triangle Institute	Camptothecin analogs as potent inhibitors of topoisomerase I
US5049668A (en) *	1989-09-15	1991-09-17	Research Triangle Institute	10,11-methylenedioxy-20(RS)-camptothecin analogs
US5180722A (en) *	1987-04-14	1993-01-19	Research Triangle Institute	10,11-methylenedioxy-20(RS)-camptothecin and 10,11-methylenedioxy-20(S)-camptothecin analogs
US5340817A (en) *	1987-04-14	1994-08-23	Research Triangle Institute	Method of treating tumors with anti-tumor effective camptothecin compounds
US5122606A (en) *	1987-04-14	1992-06-16	Research Triangle Institute	10,11-methylenedioxy camptothecins
US4939255A (en) *	1987-06-24	1990-07-03	Daiichi Pharmaceutical Co., Ltd.	Hexa-cyclic camptothecin derivatives
US5552154A (en) *	1989-11-06	1996-09-03	The Stehlin Foundation For Cancer Research	Method for treating cancer with water-insoluble s-camptothecin of the closed lactone ring form and derivatives thereof
JP2684104B2 (ja) *	1990-02-09	1997-12-03	株式会社ヤクルト本社	新規なカンプトテシン誘導体
DK0547165T3 (da) *	1990-09-28	2000-03-27	Smithkline Beecham Corp	Fremgangsmåde til fremstilling af vandopløselige camptothecinanaloger såvel som forbindelserne 10-hydroxy-11-C(1-6)-alkoxyc
US5883255A (en) *	1990-10-31	1999-03-16	Smithkline Beecham Corporation	Substituted indolizino 1,2-b!quinolinones
DK1707568T3 (da) *	1991-02-21	2010-11-08	Glaxosmithkline Llc	Farmaceutisk sammensætning til anvendelse i behandlingen af ovariecancer hos et menneske, der har sygdommen
JPH06505487A (ja) *	1991-02-21	1994-06-23	スミスクライン・ビーチャム・コーポレイション	食道癌の治療用医薬組成物
CA2103707C (fr) *	1991-02-21	2003-12-09	Randall Keith Johnson	Traitement des carcinomes pulmonaires autres que le cancer pulmonaire a petites cellules
ATE136898T1 (de) *	1991-10-29	1996-05-15	Glaxo Wellcome Inc	Wasserlösliche camptothecinderivate
US5559235A (en) *	1991-10-29	1996-09-24	Glaxo Wellcome Inc.	Water soluble camptothecin derivatives
NZ245112A (en) *	1991-11-15	1995-07-26	Smithkline Beecham Corp	Pharmaceutical composition comprising a camptothecin analog and a platinum coordination compound
AU2394392A (en) *	1991-12-10	1993-07-19	Smithkline Beecham Corporation	Treatment of colorectal cancer
US6080751A (en) *	1992-01-14	2000-06-27	The Stehlin Foundation For Cancer Research	Method for treating pancreatic cancer in humans with water-insoluble S-camptothecin of the closed lactone ring form and derivatives thereof
US5446047A (en) *	1992-07-23	1995-08-29	Sloan-Kettering Institute For Cancer Research	Camptothecin analogues
US5391745A (en) *	1992-07-23	1995-02-21	Sloan-Kettering Institute For Cancer Research	Methods of preparation of camptothecin analogs
CA2142831A1 (fr) *	1992-08-21	1994-03-03	Arthur B. Pardee	Traitement des infections virales humaines
US5614549A (en) *	1992-08-21	1997-03-25	Enzon, Inc.	High molecular weight polymer-based prodrugs
US5342947A (en) *	1992-10-09	1994-08-30	Glaxo Inc.	Preparation of water soluble camptothecin derivatives
AP9300587A0 (en) *	1992-11-12	1995-05-05	Glaxo Inc	Water soluble camptothecin derivatives.
US5674872A (en) *	1993-08-20	1997-10-07	Smithkline Beecham Corporation	Treatment of ovarian cancer
AU8052194A (en) *	1993-10-20	1995-05-08	Enzon, Inc.	2'- and/or 7- substituted taxoids
US5880131A (en) *	1993-10-20	1999-03-09	Enzon, Inc.	High molecular weight polymer-based prodrugs
US5436243A (en) *	1993-11-17	1995-07-25	Research Triangle Institute Duke University	Aminoanthraquinone derivatives to combat multidrug resistance
US5447936A (en) *	1993-12-22	1995-09-05	Bionumerik Pharmaceuticals, Inc.	Lactone stable formulation of 10-hydroxy 7-ethyl camptothecin and methods for uses thereof
GB9402934D0 (en) *	1994-02-16	1994-04-06	Erba Carlo Spa	Camptothecin derivatives and process for their preparation
US5468754A (en) *	1994-04-19	1995-11-21	Bionumerik Pharmaceuticals, Inc.	11,7 substituted camptothecin derivatives and formulations of 11,7 substituted camptothecin derivatives and methods for uses thereof
CA2188297C (fr) *	1994-04-28	2006-12-19	Frederick Herman Hausheer	Formulation stable sous forme lactone de camptothecine ou 7-ethyle camptothecine
US5604233A (en) *	1994-04-28	1997-02-18	Bionumerik Pharmaceuticals, Inc.	Lactone stable formulation of 7-ethyl camptothecin and methods for uses thereof
US5597829A (en) *	1994-05-09	1997-01-28	Bionumerik Pharmaceuticals, Inc.	Lactone stable formulation of camptothecin and methods for uses thereof
US5491237A (en) *	1994-05-03	1996-02-13	Glaxo Wellcome Inc.	Intermediates in pharmaceutical camptothecin preparation
US5834442A (en) *	1994-07-07	1998-11-10	Barbara Ann Karmanos Cancer Institute	Method for inhibiting cancer metastasis by oral administration of soluble modified citrus pectin
US5646159A (en) *	1994-07-20	1997-07-08	Research Triangle Institute	Water-soluble esters of camptothecin compounds
US6504029B1 (en) *	1995-04-10	2003-01-07	Daiichi Pharmaceutical Co., Ltd.	Condensed-hexacyclic compounds and a process therefor
GB9510716D0 (en) *	1995-05-26	1995-07-19	Pharmacia Spa	Substituted camptothecin derivatives and process for their preparation
US5663177A (en) *	1995-05-31	1997-09-02	Smithkline Beecham Corporation	Water soluble camptothecin analogs
US5670500A (en) *	1995-05-31	1997-09-23	Smithkline Beecham Corporation	Water soluble camptothecin analogs
WO1996040886A1 (fr) *	1995-06-07	1996-12-19	Thomas Jefferson University	Agents antifongiques et leurs procedes d'identification et d'utlisation
AU7732996A (en) *	1995-11-22	1997-06-11	Research Triangle Institute	Camptothecin compounds with combined topoisomerase i inhibition and dna alkylation properties
US6395541B1 (en)	1996-05-23	2002-05-28	The Rockefeller University	Methods for the identification of compounds capable of inhibiting HIV-1 viral replication employing murine cell lines expressing human topoisomerase I
DE69728152T2 (de) *	1996-08-19	2004-08-05	Bionumerik Pharmaceuticals, Inc., San Antonio	Hoch-lipophile campothecin-derivate
US6013505A (en) *	1996-10-08	2000-01-11	Smithkline Beecham Corporation	Topoisomerase I
US5962303A (en)	1996-10-15	1999-10-05	Smithkline Beecham Corporation	Topoisomerase III
US6025156A (en) *	1996-10-15	2000-02-15	Smithkline Beecham Corporation	Topoisomerase III
US6559309B2 (en)	1996-11-01	2003-05-06	Osi Pharmaceuticals, Inc.	Preparation of a camptothecin derivative by intramolecular cyclisation
CA2280905C (fr) *	1997-02-14	2006-08-29	Bionumerik Pharmaceuticals, Inc.	Derives de camptothecine hautement lipophile
US6207673B1 (en)	1997-03-12	2001-03-27	The University Of North Carolina At Chapel Hill	Covalent conjugates of topoisomerase I and topoisomerase II inhibitors
ID23424A (id)	1997-05-14	2000-04-20	Bayer Ag	Glikokonjugat dari 20(s)-kamptotesin
US6046209A (en) *	1997-05-27	2000-04-04	Smithkline Beecham Corporation	Water soluble camptothecin analogs
TW458974B (en) *	1997-07-17	2001-10-11	Kuraray Co	Process for producing chromans
US6011042A (en) *	1997-10-10	2000-01-04	Enzon, Inc.	Acyl polymeric derivatives of aromatic hydroxyl-containing compounds
US6214821B1 (en)	1998-03-05	2001-04-10	Washington State University Research Foundation	Methods and composition for the inhibition of cancer cells
DK1102594T3 (da) *	1998-08-05	2002-08-26	Aventis Pharma Sa	Anvendelse af natriumchlorid til nedsættelse af den gastrointestinale toxicitet af derivater af camptothecin
HK1049787B (en)	1999-10-01	2014-07-25	Immunogen, Inc.	Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents
FR2801309B1 (fr) *	1999-11-18	2002-01-04	Adir	Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US6288072B1 (en) *	1999-12-29	2001-09-11	Monroe E. Wall	Camptothecin β-alanine esters with topoisomerase I inhibition
IL150953A0 (en)	2000-02-28	2003-02-12	Aventis Pharma Sa	A composition comprising camptothecin and a pyrimidine derivative for the treatment of cancer
US6545010B2 (en)	2000-03-17	2003-04-08	Aventis Pharma S.A.	Composition comprising camptothecin or a camptothecin derivative and a platin derivative for the treatment of cancer
US6548488B2 (en)	2000-03-17	2003-04-15	Aventis Pharma S.A.	Composition comprising camptothecin or a camptothecin derivative and an alkylating agent for the treatment of cancer
AR027687A1 (es) *	2000-03-22	2003-04-09	Yakult Honsha Kk	Procedimiento para preparar camptotecina
US6486320B2 (en)	2000-09-15	2002-11-26	Aventis Pharma S.A.	Preparation of camptothecin and of its derivatives
KR100742524B1 (ko)	2000-10-27	2007-08-02	아방티 파르마 소시에테 아노님	캄프토테신과 스틸벤 유도체를 포함하는 암 치료용 약제학적 병용제제
US20050003502A1 (en) *	2000-11-14	2005-01-06	Emerald Biostructures, Inc.	Structures and methods for designing topoisomerase I inhibitors
IL163666A0 (en)	2002-02-22	2005-12-18	New River Pharmaceuticals Inc	Active agent delivery systems and methods for protecting and administering active agents
US7462601B2 (en) *	2002-03-26	2008-12-09	Tsutomu Kagiya	Ameliorant for chemical treatment of cancer
ITRM20020306A1 (it) *	2002-05-31	2003-12-01	Sigma Tau Ind Farmaceuti	Esteri in posizione 20 di camptotecine.
US20040062748A1 (en) *	2002-09-30	2004-04-01	Mountain View Pharmaceuticals, Inc.	Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof
US8129330B2 (en) *	2002-09-30	2012-03-06	Mountain View Pharmaceuticals, Inc.	Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof
US8034831B2 (en) *	2002-11-06	2011-10-11	Celgene Corporation	Methods for the treatment and management of myeloproliferative diseases using 4-(amino)-2-(2,6-Dioxo(3-piperidyl)-isoindoline-1,3-dione in combination with other therapies
US7563810B2 (en)	2002-11-06	2009-07-21	Celgene Corporation	Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases
WO2004055020A1 (fr) *	2002-12-16	2004-07-01	Council Of Scientific And Industrial Research	Procede de preparation directe d'analogues de 5-alcoxy et de 5-acyloxy de camptothecines ou de mappicines cetones
FR2852606A1 (fr) *	2003-03-18	2004-09-24	Inst Nat Sante Rech Med	Moyens pour inhiber simultanement l'expression de plusieurs genes impliques dans une pathologie
AU2003223109A1 (en) *	2003-03-31	2004-10-25	Council Of Scientific And Industrial Research	Process for preparing topotecan from 10-hydroxy-4-(s) camptothecin
CN100406460C (zh) *	2003-11-10	2008-07-30	中国科学院上海药物研究所	喜树碱的新衍生物、制备方法和用途
AR046579A1 (es) *	2003-11-12	2005-12-14	Smithkline Beecham Corp	Compuesto cristalino de topotecan, composicion farmaceutica que lo comprende, procedimiento para prepararlo y su uso para preparar dicha composicion farmaceutica
DE602005027673D1 (de) *	2004-03-05	2011-06-09	Vegenics Pty Ltd	Materialien und verfahren für wachstumsfaktorbindende konstrukte
AU2005244768B2 (en)	2004-04-27	2011-06-09	Wellstat Biologics Corporation	Cancer treatment using viruses and camptothecins
US20050267141A1 (en)	2004-05-28	2005-12-01	Phytogen Life Sciences Inc.	Process to prepare camptothecin derivatives
US20050272757A1 (en) *	2004-06-04	2005-12-08	Phytogen Life Sciences Inc.	Process to prepare camptothecin derivatives and novel intermediate and compounds thereof
US7122700B2 (en) *	2004-07-30	2006-10-17	Xerox Corporation	Arylamine processes
US20090104254A1 (en)	2004-12-22	2009-04-23	Rutgers, The State University Of New Jersey	Controlled Release Hydrogels
AU2006207321B2 (en)	2005-01-21	2012-09-06	Astex Therapeutics Limited	Pharmaceutical compounds
US20090047365A1 (en) *	2005-02-28	2009-02-19	Eisai R & D Management Co., Ltd.	Novel Concomitant Use of Sulfonamide Compound with Anti-Cancer Agent
AU2006270297B2 (en) *	2005-07-14	2013-01-17	Wellstat Biologics Corporation	Cancer treatment using viruses, fluoropyrimidines and camptothecins
WO2007042799A1 (fr) *	2005-10-10	2007-04-19	Cipla Limited	Nouvelles formes cristallines
US7786134B2 (en)	2005-12-16	2010-08-31	Sonus Pharmaceuticals, Inc.	Lipophilic anticancer drug compounds, compositions and related methods
US7547785B2 (en)	2005-12-26	2009-06-16	Dr. Reddy's Laboratories Limited	Process for preparing topotecan
WO2007085370A1 (fr) *	2006-01-25	2007-08-02	Heidelberg Pharma Ag	Dérivés d’esters lipidiques de la 9-(dimethylamino)methyl-10-hydroxycamptothecine
CN101033230B (zh) *	2006-03-10	2010-12-08	中国科学院上海药物研究所	一类喜树碱衍生物及其应用
EP1998809B1 (fr)	2006-03-30	2014-06-25	Drais Pharmaceuticals, Inc.	Conjugués de camptothecin et peptide pénétrant la cellule et composition pharmaceutique les contenant.
US20070259031A1 (en) *	2006-04-26	2007-11-08	The Regents Of The University Of California	Compositions and methods for convection enhanced delivery of high molecular weight neurotherapeutics
WO2008021549A2 (fr) *	2006-08-18	2008-02-21	Sidney Kimmel Cancer Center	Procédés et compositions pour la suppression de tumeurs modulées par la topoisomérase i
JP5528806B2 (ja)	2006-10-12	2014-06-25	アステックス、セラピューティックス、リミテッド	複合薬剤
JP5528807B2 (ja)	2006-10-12	2014-06-25	アステックス、セラピューティックス、リミテッド	複合薬剤
US7977483B2 (en) *	2007-04-11	2011-07-12	Scinopharm Taiwan, Ltd.	Process for making topotecan
US20080255175A1 (en) *	2007-04-16	2008-10-16	Lam Marina K	Anti-cancer agents, compositions and methods of treating cancers
NZ580516A (en) *	2007-04-19	2012-02-24	Scinopharm Taiwan Ltd	Crystalline forms of topotecan hydrochloride and processes for making the same
US8026249B2 (en) *	2007-09-14	2011-09-27	Deutena Pharmaceuticals, Inc.	Deuterium-enriched topotecan
ITMI20072268A1 (it)	2007-12-04	2009-06-05	Antibioticos Spa	Polimorfi cristallini di topotecan cloridrato con elevato grado di purezza e metodi per la loro preparazione
EP2280013B1 (fr) *	2008-05-29	2013-07-10	MicroBiopharm Japan Co., Ltd.	Procédé de production de dérivé de camptothécine
US8173621B2 (en)	2008-06-11	2012-05-08	Gilead Pharmasset Llc	Nucleoside cyclicphosphates
CA2748057C (fr) *	2008-12-23	2018-07-03	Pharmasset, Inc.	Phosphoramidates de nucleosides
EP2376515A1 (fr)	2008-12-23	2011-10-19	Pharmasset, Inc.	Synthèse de nucléosides de type purine
US8551973B2 (en) *	2008-12-23	2013-10-08	Gilead Pharmasset Llc	Nucleoside analogs
WO2011116026A2 (fr)	2010-03-15	2011-09-22	The Board Of Trustees Of The University Of Illinois	Inhibiteurs des interactions de liaison de sous unité alpha d'intégrine ƒà-de protéine g
CL2011000718A1 (es)	2010-03-31	2012-04-09	Gilead Pharmasset Llc	Proceso para la preparacion de compuestos fosforados enantiomericos.
US20140086975A1 (en)	2010-10-15	2014-03-27	Rutgers, The State University Of New Jersey	Hydrogel formulation for dermal and ocular delivery
RU2447076C1 (ru) *	2010-12-09	2012-04-10	Закрытое Акционерное Общество "Фарм-Синтез"	Способ получения топотекана
US20140371258A1 (en)	2010-12-17	2014-12-18	Nektar Therapeutics	Water-Soluble Polymer Conjugates of Topotecan
WO2012082337A2 (fr)	2010-12-17	2012-06-21	Glaxo Wellcome Manufacturing Pte Ltd	Combinaison
EP2655401B1 (fr)	2010-12-20	2016-03-09	The Regents of the University of Michigan	Inhibiteurs de l'interaction de liaison entre le récepteur du facteur de croissance épidermique et la protéine de choc thermique 90
US20130303560A1 (en)	2011-02-01	2013-11-14	Sunnybrook Research Institute	Combination
TR201808733T4 (tr)	2011-10-03	2018-07-23	Mx Adjuvac Ab	Kanser tedavisini ve gıda ile ilgili bileşikleri içeren tıp alanlarında amfipatik veya hidrofobik moleküller için taşıyıcı olarak nano-parçacıklar, preparasyon için proses ve bunların kullanımı.
PL235836B1 (pl) *	2012-10-25	2020-11-02	Inst Chemii Organicznej Polskiej Akademii Nauk	Pochodne kamptotecyny, sposób ich otrzymywania i zastosowanie
CN103113381B (zh) *	2013-02-26	2014-12-10	大连理工大学	系列水溶性羟基喜树碱环烷胺醇衍生物及其制法与用途
WO2014163558A1 (fr)	2013-04-01	2014-10-09	Moreinx Ab	Nanoparticules, constituées de stérol et de saponine de quillaja saponaria molina, leur procédé de préparation et leur utilisation comme support pour des molécules amphipathiques ou hydrophobes dans le domaine médical, notamment pour le traitement du cancer, et composés alimentaires
WO2016123143A1 (fr)	2015-01-26	2016-08-04	The University Of Chicago	Lymphocytes t à récepteur d'antigène chimérique (car) reconnaissant le récepteur il 13rα2 spécifique au cancer
JP7264592B2 (ja)	2015-01-26	2023-04-25	ザユニバーシティーオブシカゴ	ＩＬ１３Ｒα２結合剤及び癌治療におけるその使用
WO2017053920A1 (fr)	2015-09-25	2017-03-30	Zy Therapeutics Inc.	Formulation médicamenteuse à base de particules comprenant un conjugué polysaccharide-vitamine
CN120661674A (zh)	2016-03-15	2025-09-19	奥莱松基因组股份有限公司	用于治疗实体瘤的lsd1抑制剂的组合
EP3622953B1 (fr) *	2016-05-17	2021-03-17	Scandion Oncology A/S	Polythérapie du cancer
MX2020001451A (es)	2017-08-07	2020-08-06	Amgen Inc	Tratamiento de cancer de mama triple negativo o cancer colorrectal con metastasis hepaticas con un anticuerpo anti-pd-l1 y un virus oncolitico.
EP3669890A1 (fr)	2018-12-18	2020-06-24	Croda International PLC	Nanoparticules filamenteuses ayant un effet d'adjuvant de vaccin
DK3941946T3 (da)	2019-03-20	2025-03-24	Univ California	Claudin-6-antistoffer og lægemiddelkonjugater
EP3941944A4 (fr)	2019-03-20	2022-11-30	The Regents of the University of California	Anticorps de claudin-6 bispécifiques
US20220160872A1 (en)	2019-04-09	2022-05-26	The Board Of Trustees Of The University Of Illinois	Drug Adsorbed Highly Porous Activated Carbon for Enhanced Drug Delivery
JP2022530241A (ja)	2019-04-30	2022-06-28	インスチトゥートデメディシーナモリクラールジョアンロボアントゥネス	Ｃｄｋ阻害剤と組み合わせたｒａｎｋ経路阻害剤
US12558407B2 (en)	2019-05-02	2026-02-24	University Of Florida Research Foundation, Inc.	Compositions for treatment of diffuse intrinsic pontine glioma
EP3986441A1 (fr)	2019-06-24	2022-04-27	Amgen Inc.	Inhibition de la sirp-gamma pour le traitement du cancer
WO2021043723A1 (fr)	2019-09-02	2021-03-11	INSERM (Institut National de la Santé et de la Recherche Médicale)	Procédés et compositions pour le traitement d'une maladie associée à une déficience de pax6
BR112022017064A2 (pt) *	2020-02-25	2022-11-16	Mediboston Inc	Derivados da camptotecina e seus conjugados
US12521444B2 (en)	2021-02-25	2026-01-13	Fortvita Biologics Limited	Anti-HER2 antibody-drug conjugates and uses thereof
KR20250008774A (ko)	2022-05-11	2025-01-15	셀진 코포레이션	T 세포 요법 및 그의 생산과 관련된 방법 및 용도
CN116478174B (zh) *	2022-07-29	2025-09-16	杭州爱科瑞思生物医药有限公司	喜树碱衍生物及其制备方法和应用
CN117045655A (zh) *	2023-03-09	2023-11-14	兰州大学	喜树碱类衍生物在制备治疗膀胱癌药物中的应用

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4399282A (en) *	1979-07-10	1983-08-16	Kabushiki Kaisha Yakult Honsha	Camptothecin derivatives
US4342776A (en) *	1979-11-05	1982-08-03	Merck & Co., Inc.	4-Substituted-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase
US4473692A (en) *	1981-09-04	1984-09-25	Kabushiki Kaisha Yakult Honsha	Camptothecin derivatives and process for preparing same
JPS58134095A (ja) *	1982-02-05	1983-08-10	Yakult Honsha Co Ltd	新規なカンプトテシン誘導体
JPS58154582A (ja) *	1982-03-10	1983-09-14	Yakult Honsha Co Ltd	新規なカンプトテシン誘導体およびその製造法
JPS58154584A (ja) *	1982-03-10	1983-09-14	Yakult Honsha Co Ltd	５位ヒドロキシ置換カンプトテシン誘導体の製造法
JPS5951289A (ja) *	1982-09-17	1984-03-24	Yakult Honsha Co Ltd	新規な９−置換−カンプトテシン誘導体
JPS59227884A (ja) *	1983-06-09	1984-12-21	Yakult Honsha Co Ltd	新規な７−ヒドロキシアルキルカンプトテシン誘導体
JPS6019790A (ja) *	1983-07-14	1985-01-31	Yakult Honsha Co Ltd	新規なカンプトテシン誘導体
US4775759A (en) *	1984-11-27	1988-10-04	The United States Of America As Represented By The Department Of Health And Human Services	Synthesis and utilization of 17-methyl and 17-cyclopropylmethyl-3,14-dihydroxy-4,5α-epoxy 6β-fluoromorphinans (foxy and cyclofoxy) as (18F)-labeled opioid ligands for position emission transaxial tomography (PETT)
US4820816A (en) *	1985-08-02	1989-04-11	President And Fellows Of Harvard College	3-trifuoromethylsulfonyloxy-substituted 1-carbacephalosporins as intermediates for antibiotics
JPH0615546B2 (ja) *	1986-02-24	1994-03-02	株式会社ヤクルト本社	新規なカンプトテシン誘導体
US4894456A (en) *	1987-03-31	1990-01-16	Research Triangle Institute	Synthesis of camptothecin and analogs thereof
JP3431931B2 (ja) *	1992-07-16	2003-07-28	旭電化工業株式会社	銅及び銅合金の表面処理方法

1988
- 1988-11-02 US US07/266,460 patent/US5004758A/en not_active Expired - Lifetime
- 1988-11-28 IL IL8851788A patent/IL88517A/en not_active IP Right Cessation
- 1988-11-28 DK DK198806636A patent/DK173034B1/da not_active IP Right Cessation
- 1988-11-29 ZA ZA888938A patent/ZA888938B/xx unknown
- 1988-11-29 PT PT89111A patent/PT89111B/pt not_active IP Right Cessation
- 1988-11-29 NZ NZ227124A patent/NZ227124A/en unknown
- 1988-11-30 IE IE357688A patent/IE74873B1/en not_active IP Right Cessation
- 1988-11-30 AT AT88311366T patent/ATE143368T1/de active
- 1988-11-30 AU AU26394/88A patent/AU612735B2/en not_active Expired
- 1988-11-30 ES ES88311366T patent/ES2094721T3/es not_active Expired - Lifetime
- 1988-11-30 DE DE3855575T patent/DE3855575T2/de not_active Expired - Lifetime
- 1988-11-30 SG SG1996005126A patent/SG66254A1/en unknown
- 1988-11-30 DE DE1997175017 patent/DE19775017I2/de active Active
- 1988-11-30 NO NO885352A patent/NO170487C/no not_active IP Right Cessation
- 1988-11-30 LU LU90026C patent/LU90026I2/fr unknown
- 1988-11-30 EP EP88311366A patent/EP0321122B1/fr not_active Expired - Lifetime
- 1988-11-30 CA CA000584544A patent/CA1308102C/fr not_active Expired - Lifetime
- 1988-11-30 FI FI885569A patent/FI89923C/fi not_active IP Right Cessation
- 1988-12-01 CN CN88108256A patent/CN1027265C/zh not_active Expired - Lifetime
- 1988-12-01 KR KR1019880015971A patent/KR930009357B1/ko not_active Expired - Lifetime
- 1988-12-01 JP JP63306769A patent/JPH0633268B2/ja not_active Expired - Lifetime
1992
- 1992-06-29 MX MX9203744A patent/MX9203744A/es unknown
1993
- 1993-02-27 CN CN93102886A patent/CN1035380C/zh not_active Expired - Lifetime
- 1993-06-28 CN CN93107879A patent/CN1037574C/zh not_active Expired - Lifetime
1996
- 1996-12-11 GR GR960403426T patent/GR3021990T3/el unknown
1997
- 1997-03-27 NL NL970017C patent/NL970017I2/nl unknown
- 1997-04-16 LU LU90053C patent/LU90053I2/fr unknown
- 1997-06-12 HK HK81097A patent/HK81097A/en not_active IP Right Cessation
1998
- 1998-01-15 NO NO1998003C patent/NO1998003I1/no unknown
- 1998-02-20 CY CY201798A patent/CY2017A/xx unknown

Also Published As

Publication number	Publication date
IL88517A0 (en)	1989-06-30
HK81097A (en)	1997-06-20
FI89923C (fi)	1993-12-10
US5004758A (en)	1991-04-02
JPH01186893A (ja)	1989-07-26
CN1034724A (zh)	1989-08-16
NO885352L (no)	1989-06-02
CN1035380C (zh)	1997-07-09
DE19775017I2 (de)	2002-11-07
IE883576L (en)	1989-06-01
SG66254A1 (en)	1999-07-20
DK663688A (da)	1989-06-02
CA1308102C (fr)	1992-09-29
FI885569A0 (fi)	1988-11-30
PT89111A (pt)	1989-12-29
EP0321122A2 (fr)	1989-06-21
ATE143368T1 (de)	1996-10-15
NO170487C (no)	1992-10-21
ES2094721T3 (es)	1997-02-01
ZA888938B (en)	1990-03-28
LU90053I2 (fr)	1997-07-01
CN1027265C (zh)	1995-01-04
NO1998003I1 (no)	1998-01-15
LU90026I2 (fr)	1997-04-22
CN1083817A (zh)	1994-03-16
EP0321122A3 (fr)	1990-12-27
CY2017A (en)	1998-02-20
JPH0633268B2 (ja)	1994-05-02
NO885352D0 (no)	1988-11-30
MX9203744A (es)	1992-09-01
GR3021990T3 (en)	1997-03-31
CN1037574C (zh)	1998-03-04
PT89111B (pt)	1994-01-31
NL970017I2 (nl)	1997-09-01
AU2639488A (en)	1989-06-01
KR890009934A (ko)	1989-08-05
DE3855575T2 (de)	1997-03-20
NZ227124A (en)	1991-12-23
FI885569L (fi)	1989-06-02
FI89923B (fi)	1993-08-31
DK663688D0 (da)	1988-11-28
EP0321122B1 (fr)	1996-09-25
DE3855575D1 (de)	1996-10-31
AU612735B2 (en)	1991-07-18
KR930009357B1 (ko)	1993-09-28
NL970017I1 (nl)	1997-06-02
CN1087637A (zh)	1994-06-08
DK173034B1 (da)	1999-11-29
IE74873B1 (en)	1997-08-13
NO170487B (no)	1992-07-13

Legal Events

Date	Code	Title
2003-02-12	KB	Patent renewed
2006-12-27	KB	Patent renewed
2009-07-20	EXP	Patent expired

Publication	Publication Date	Title
IL88517A (en)	1994-10-07	Water soluble camptothecin analogs, their preparation, pharmaceutical compositions containing them, some intermediates thereof and their preparation
RU2262339C2 (ru)	2005-10-20	Производные индолил-3-глиоксиловой кислоты - соединения, обладающие противоопухолевой активностью, фармацевтическая композиция, противоопухолевое средство (варианты)
US5597831A (en)	1997-01-28	6-[X-(2-hydroxyethyl) aminoalkyl]-5,11-dioxo-5,6-dihydro-11-H-indeno[1,2-c]isoquinolines and their use as antineoplastic agents
EP3878854A1 (fr)	2021-09-15	Inhibiteur de la tyrosine kinase macrocyclique et son application
US20090326225A1 (en)	2009-12-31	Novel Process for the Preparation of Hexacyclic Compounds
AU638205B2 (en)	1993-06-24	Optically pure r-(-)-niguldipine and its derivatives for treating tumorous diseases
MXPA06011679A (es)	2007-01-23	Novedosos profarmacos solubles en agua.
US20050209263A1 (en)	2005-09-22	7-Substituted camptothecin and camptothecin analogs and methods for producing the same
EP0643699B1 (fr)	1996-10-23	6-(2-hydroxyethylaminoalkyl)-5,11-dioxo-5,6-dihydro-11h- indeno[1,2-c]isoquinoleines et leur utilisation comme agents anticancereux
CN116768903B (zh)	2025-05-09	一种吡咯并嘧啶衍生物及其制备方法、药物组合物和应用
AU2002356720B2 (en)	2009-01-29	Hexacyclic compounds
ES2401563T3 (es)	2013-04-22	Derivados de metilendioxibenzo [I]fenantridina usados para tratar el cáncer
CN108484637A (zh)	2018-09-04	靶向抗癌新药x-76成盐化合物及其用途、制备方法
US11839216B1 (en)	2023-12-12	Quinoline-2,3-fused nine-membered ring scaffold compound, and preparation method and application thereof as effective component in plant fungicide
SK397391A3 (sk)	2000-12-11	9,10-Substituované kamptotecíny, farmaceutický prípravok s ich obsahom a medziprodukt
US7071204B2 (en)	2006-07-04	Camptothecin analogs having an E-ring ketone
CN112704683A (zh)	2021-04-27	一种新型喜树碱衍生物及其制备抗肿瘤药物的应用
Umarani et al.	2011	Exploring the effects of newer three component aminobenzylated reactions of triphenyl imidazole motif as potent antimicrobial and anti-inflammatory agents