ITRM930334A1 - Tassano ad attivita' antitumorale. - Google Patents
Tassano ad attivita' antitumorale. Download PDFInfo
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- ITRM930334A1 ITRM930334A1 IT000334A ITRM930334A ITRM930334A1 IT RM930334 A1 ITRM930334 A1 IT RM930334A1 IT 000334 A IT000334 A IT 000334A IT RM930334 A ITRM930334 A IT RM930334A IT RM930334 A1 ITRM930334 A1 IT RM930334A1
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- acetone
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- 230000001093 anti-cancer Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 241000196324 Embryophyta Species 0.000 claims abstract description 7
- 241001116500 Taxus Species 0.000 claims abstract description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 4
- HKXCCCPZQFXXGM-UONOGXRCSA-N (2r,3s)-3-(hexanoylamino)-2-hydroxy-3-phenylpropanoic acid Chemical compound CCCCCC(=O)N[C@H]([C@@H](O)C(O)=O)C1=CC=CC=C1 HKXCCCPZQFXXGM-UONOGXRCSA-N 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 150000002148 esters Chemical group 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 230000005526 G1 to G0 transition Effects 0.000 claims description 2
- 241001674343 Taxus x media Species 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- 239000004480 active ingredient Substances 0.000 claims 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims 1
- 238000013375 chromatographic separation Methods 0.000 claims 1
- 238000001704 evaporation Methods 0.000 claims 1
- 230000008020 evaporation Effects 0.000 claims 1
- 238000005194 fractionation Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000002798 polar solvent Substances 0.000 claims 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 abstract description 9
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 abstract description 7
- 229930012538 Paclitaxel Natural products 0.000 abstract description 6
- 229960001592 paclitaxel Drugs 0.000 abstract description 6
- 229940123237 Taxane Drugs 0.000 abstract description 5
- 230000000259 anti-tumor effect Effects 0.000 abstract description 2
- 239000000063 antileukemic agent Substances 0.000 abstract 1
- 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 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 235000020853 Inedia Nutrition 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000282346 Meles meles Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 229930004069 diterpene Natural products 0.000 description 1
- 150000004141 diterpene derivatives Chemical class 0.000 description 1
- DRNBLNIUGKCELA-UHFFFAOYSA-N ethenol hydrochloride Chemical compound C=CO.Cl DRNBLNIUGKCELA-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000029305 taxis Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
"TASSANO AD ATTIVIT?' ANTITUMORALE"
La presente invenzione ha per oggetto un nuovo diterpene a nucleo tassanico dotato di attivit? antitumorale. Sulla base di analisi spettrometriche al. nuovo composto conpete la struttura (1) corrispondente all'estere in posizione 13 del 5B,20-epossi-
esaidro ssitass-ll-en-9-cne 4,10-diacetato 2-benzoato
con la (2R,3S)-N-esanoil-3-fenilisoserina.
00033*
Il composto di struttura (1) viene isolato con rese conprese fra lo 0,02 e lo 0,06% per estrazione della corteccia della radice di piante del genere Taxus.
Il materiale vegetale da cui (1) viene estratto ? costituito preferenzialmente da corteccia della radici di cultivar di tasso, per esenpio corteccia di Taxus inedia cv Hicksii. Questo cultivar ? correntemente impiegato ccn scopi ornamentali per l'allestimento di giardini. Ci? consente di evitare la raccolta indiscriminata delle radici delle piante spontanee di tasso, la cui crescita ? notoriamente lenta, e conseguentemente la loro rapida estinzione.
Per l'estrazione del composto (1) si utilizzano solventi clorurati, per esempio die loromet ano , puri o in miscela ccn alcoli, per esempio alcol metilico ed etilico. L'estrazione del materiale vegetale pu? essere condotta anche con 11 impiego di chetoni, per esempio acetone, puri o in miscela con acqua.
L'estratto della corteccia delle radici contiene, accanto al composto (1) , una serie di altri noti tassani, quali il tasso lo (2) , la cefalomannina (3) e i loro rispettivi 10-<3eacetilderivati (4) e (5) . La separazione di (1) da questi tassani richiede una purificazione per cromatografia su colonna.
A questo scopo viene utilizzato preferenzialmente gel di silice come fase stazionaria. Come eluenti si impiegano miscele di solventi costituite da un idrocarburo alifatico, per esempio n-esano, cicloesano o n-eptano, o aromatico, per esempio toluene, con un solvente di maggiore polarit?, quale ad esempio etile acetato o acetone.
Il ccnposto (1), ricuperato dalla frazioni cromatografiche che lo contengono, viene isolato dopo cristallizzazione da acetone oppure da etere diisopropilico o da loro miscele con n-esano o n-eptano.
Il nuovo ccnposto (1) presenta notevoli affinit? strutturali col farmaco antitumorale tassolo (2), dal quale differisce per la natura della catena laterale legata in posizione 13 del nucleo tassanico. Pertanto, il composto (1) pu? divenire accessibile, oltre ?he per estrazione del materiale vegetale, per semisintesi attraverso processi analoghi a quelli impiegati per la produzione del tassolo (2) (cfr. I. Ojima et al, Tetrahedrcn 48, 6985, 1992).
Poich? il composto (1) presenta affinit? strutturali con il tassolo (2), si poteva prevedere che esso possedesse attivit? antitumorali analoghe.
In effetti, l'attivit? in vitro di (1) nei ccnfronti di diverse linee tumorali, per esempio quella riguardante il tumore del seno, del polmone, del colon e dell'ovaio, ? paragonabile a quella del tassolo, come appare dai risultati riportati in Tab. 1. Tuttavia, il nuovo tassano (1) mostra sorprendentemente una maggiore attivit? rispetto al tassolo in relazione a cellule tumorali resistenti all'adriamicina (ADR) e a cellule leucemiche.
Tab. 1 - Confronto dell'attivit? antiblastica del Tassano (1) e <fel Tas solo (2) su diverse linee tumorali {IC50 , nM) .
In studi in vivo il composto (1) , s curmi nistrato in soluzioni acquose contenenti Cremophor?,; si ? dimostrato efficace verso i tumori impiantati nel topo nudo. Il tassano (1) si propone pertanto come farmaco antitunorale per il trattamento di tumori liquidi e di tumori resistenti a farmaci quali l'adriamicina.
In base ai dosaggi attivi riscontrati nell'animale la dose del composto (1) nell'uomo dovrebbe essere compresa fra 150-250 mg/m a cicli ripetuti a distanza di due o tre settimane fino a scomparsa metastatica.
L'esenpio sotto riportato illustra la preparazione del prodotto oggetto della presente invenzione.
Esempio 1
Estere in posizione 13 del
esaidrossitass-ll-en-9-one 4 ,10-diacetato 2-benzoato con la (2R,3S)-N-esanoil-3-fenilisoserina (formula 1).
50 kg di corteccia polverizzata di Taxus media cv Hickii vengono estratti a temperatura anfaiente con 130 litri e poi per tre volte con 80 litri di cloruro di metilene-metanolo 9:1, ogni estrazione essendo condotta per 24 ore.
Gli estratti riuniti vengono concentrati a secco sotto vuoto ed il residuo (4300 g) viene ripreso con 23 litri di miscela toluene-acetone 9:1. Dopo filtrazione del materiale insolubile la soluzione viene purificata per cromatografia su colonna contenente 27 kg di gel di silice, eluendo ccn la stessa miscela solvente. Le frazione contenenti il prodotto (1) vengono riunite ed evaporate a secco sotto vuoto. Il residuo viene cristallizzato da 80 mi di miscela n-esano/acetone 1:1. Si ottengono 17,5 g di (1), p.f. 209?, [^]D - 42 (c 0,3, MeCH), M a m/z 847.
I dati spettrofotometriei del ccrrposto (1) seno i seguenti:
Claims (7)
- RIVENDICAZIONI 1. Come nuovo composto, l'estere in posizione 13 del 5S,20-epossil,2dl,4,7fi#10B,13dresaidrossitass-ll-en-9-one 4,10-diacetato 2-benzoato con la (2R,3S)-N-esanoil-3-fenilisoserina, di formula (1)
- 2. Procedimento per la preparazione del composto (1) secondo la rivendicazione 1, caratterizzato dal fatto che si sottopone materiale vegetale di cultivar di tasso a estrazione aon idrocarburi clorurati o loro miscele ccn alcoli inferiori, che si sottopone l?estratto secco, ottenuto per evaporazione del solvente, a frazionamento cromatografico impiegando cane eluenti miscele di idrocarburi alifatici o aromatici con solventi maggiormente polari, e che il composto (1) recuperato dalle frazioni cromatografiche che lo contengono viene purificato per cristallizzazione.
- 3. Procedimento secondo la rivendicazione 2, caratterizzato dal fatto che il materiale vegetale ? costituito da corteccia di radici di Taxus media cv Hicksii.
- 4. Procedimento secondo le rivendicazioni 2-3, caratterizzato dal fatto che l'estrazione viene effettuata con miscele di cloruro di metilene e metanolo.
- 5. Procedimento secondo le rivendicazioni 2-4, caratterizzato dal fatto che per la separazione cromatografica s1impiegano gel di silice cerne fase stazionaria e toluene/acetone cane eluente.
- 6. Procedimento secondo le rivendicazioni 2-5, caratterizzato dal fatto che per la cristallizzazione s'impiegano acetone, diisoprapiletere o loro miscele con n-esano o n-eptano.
- 7. Composizioni farmaceutiche ad attivit? antitimorale , contenenti cane principio attivo il composto (1) secondo la rivendicazione 1.
Priority Applications (23)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM930334A IT1261667B (it) | 1993-05-20 | 1993-05-20 | Tassano ad attivita' antitumorale. |
| US08/088,319 US5407674A (en) | 1993-05-20 | 1993-07-07 | Taxane having antitumor activity |
| DE69322619T DE69322619T2 (de) | 1993-05-20 | 1993-07-15 | Taxane mit antitumor Wirkung |
| ES93111366T ES2068166T3 (es) | 1993-05-20 | 1993-07-15 | Taxano con actividad antitumoral. |
| EP93111366A EP0625517B1 (en) | 1993-05-20 | 1993-07-15 | Taxane having antitumor activity |
| DK93111366T DK0625517T3 (da) | 1993-05-20 | 1993-07-15 | Taxan med antitumoraktivitet |
| DE0625517T DE625517T1 (de) | 1993-05-20 | 1993-07-15 | Taxane mit antitumor Wirkung. |
| AT93111366T ATE174595T1 (de) | 1993-05-20 | 1993-07-15 | Taxane mit antitumor wirkung |
| PL94307089A PL178363B1 (pl) | 1993-05-20 | 1994-05-03 | Taksan o działaniu przeciwnowotworowym |
| CA002140519A CA2140519A1 (en) | 1993-05-20 | 1994-05-03 | Taxane having antitumor activity |
| HU9500152A HU221503B (en) | 1993-05-20 | 1994-05-03 | Taxane having antitumor activity and pharmaceutical composition containing the same |
| KR1019950700197A KR100315495B1 (ko) | 1993-05-20 | 1994-05-03 | 항종양활성을갖는탁산 |
| AU67951/94A AU6795194A (en) | 1993-05-20 | 1994-05-03 | Taxane having antitumor activity |
| CZ1995122A CZ286959B6 (en) | 1993-05-20 | 1994-05-03 | Taxane, process of its preparation and pharmaceutical preparation containing thereof |
| SK60-95A SK280873B6 (sk) | 1993-05-20 | 1994-05-03 | Taxán s protinádorovou aktivitou, spôsob jeho prípravy a farmaceutický prípravok |
| CN94190306A CN1054381C (zh) | 1993-05-20 | 1994-05-03 | 具有抗癌活性的红豆杉烷，其制法及药物组合物 |
| JP7500149A JPH07509259A (ja) | 1993-05-20 | 1994-05-03 | 抗腫瘍活性を有するタクサン |
| PCT/EP1994/001405 WO1994027984A1 (en) | 1993-05-20 | 1994-05-03 | Taxane having antitumor activity |
| RU95105981A RU2129551C1 (ru) | 1993-05-20 | 1994-05-03 | 4,10-ДИАЦЕТАТ-2-БЕНЗОАТ 5β, 20-ЭПОКСИ-1,2α, 4,7; , 10β, 13α- ГЕКСАГИДРОКСИТАКС-11-ЕН-9-ОНА СО СЛОЖНОЙ ЭФИРНОЙ ГРУППОЙ В ПОЛОЖЕНИИ 13, ОБРАЗОВАННОЙ (2R, 2S)-N-ГЕКСАНОИЛ-3-ФЕНИЛИЗОСЕРИНОМ, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ |
| NO19950184A NO310510B1 (no) | 1993-05-20 | 1995-01-18 | Taxan med antitumoraktivitet |
| FI950207A FI950207A0 (fi) | 1993-05-20 | 1995-01-18 | Taksaani, jolla on kasvaimenvastaista vaikutusta |
| GR950300009T GR950300009T1 (en) | 1993-05-20 | 1995-03-31 | Taxane having antitumor activity. |
| HK98113937A HK1012628A1 (en) | 1993-05-20 | 1998-12-17 | Taxane having antitumor activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM930334A IT1261667B (it) | 1993-05-20 | 1993-05-20 | Tassano ad attivita' antitumorale. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| ITRM930334A0 ITRM930334A0 (it) | 1993-05-20 |
| ITRM930334A1 true ITRM930334A1 (it) | 1994-11-20 |
| IT1261667B IT1261667B (it) | 1996-05-29 |
Family
ID=11401772
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ITRM930334A IT1261667B (it) | 1993-05-20 | 1993-05-20 | Tassano ad attivita' antitumorale. |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US5407674A (it) |
| EP (1) | EP0625517B1 (it) |
| JP (1) | JPH07509259A (it) |
| KR (1) | KR100315495B1 (it) |
| CN (1) | CN1054381C (it) |
| AT (1) | ATE174595T1 (it) |
| AU (1) | AU6795194A (it) |
| CA (1) | CA2140519A1 (it) |
| CZ (1) | CZ286959B6 (it) |
| DE (2) | DE625517T1 (it) |
| DK (1) | DK0625517T3 (it) |
| ES (1) | ES2068166T3 (it) |
| FI (1) | FI950207A0 (it) |
| GR (1) | GR950300009T1 (it) |
| HK (1) | HK1012628A1 (it) |
| HU (1) | HU221503B (it) |
| IT (1) | IT1261667B (it) |
| NO (1) | NO310510B1 (it) |
| PL (1) | PL178363B1 (it) |
| RU (1) | RU2129551C1 (it) |
| SK (1) | SK280873B6 (it) |
| WO (1) | WO1994027984A1 (it) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4139993A1 (de) * | 1991-12-04 | 1993-06-09 | Merck Patent Gmbh, 6100 Darmstadt, De | Pigmentzubereitung |
| IT1275936B1 (it) * | 1995-03-17 | 1997-10-24 | Indena Spa | Derivati della 10-deacetilbaccatina iii e della 10-deacetil-14b- idrossibaccatina iii loro metodo di preparazione e formulazioni |
| US5756536A (en) * | 1995-11-03 | 1998-05-26 | Purdue Research Foundation | Microbial transformation of taxol and cephalomannine |
| US5965752A (en) * | 1996-08-23 | 1999-10-12 | Institut National De La Recherche Scientifique | Preparative scale isolation and purification of taxanes |
| CA2188190A1 (en) | 1996-10-18 | 1998-04-18 | Sarala Balachandran | The semi-synthesis of a protected bacatin iii compound |
| WO1998017656A1 (en) * | 1996-10-24 | 1998-04-30 | Institute Armand-Frappier | A family of canadensol taxanes, the semi-synthetic preparation and therapeutic use thereof |
| EP1229934B1 (en) | 1999-10-01 | 2014-03-05 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| US6649632B2 (en) | 2000-02-02 | 2003-11-18 | Fsu Research Foundation, Inc. | C10 ester substituted taxanes |
| BR0104779A (pt) * | 2000-02-02 | 2001-12-26 | Univ Florida State Res Found | Taxanos substituìdos com carbonato c10 comoagentes antitumor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4206221A (en) * | 1979-01-03 | 1980-06-03 | The United States Of America As Represented By The Secretary Of Agriculture | Cephalomannine and its use in treating leukemic tumors |
| US5157049A (en) * | 1988-03-07 | 1992-10-20 | The United States Of America As Represented By The Department Of Health & Human Services | Method of treating cancers sensitive to treatment with water soluble derivatives of taxol |
| US4942184A (en) * | 1988-03-07 | 1990-07-17 | The United States Of America As Represented By The Department Of Health And Human Services | Water soluble, antineoplastic derivatives of taxol |
| FR2662441B1 (fr) * | 1990-05-22 | 1992-10-23 | Rhone Poulenc Sante | Procede de preparation enantioselective de derives de la phenylisoserine. |
| US5229526A (en) * | 1991-09-23 | 1993-07-20 | Florida State University | Metal alkoxides |
| US5250683A (en) * | 1991-09-23 | 1993-10-05 | Florida State University | Certain substituted taxanes and pharmaceutical compositions containing them |
| US5227400A (en) * | 1991-09-23 | 1993-07-13 | Florida State University | Furyl and thienyl substituted taxanes and pharmaceutical compositions containing them |
| US5243045A (en) * | 1991-09-23 | 1993-09-07 | Florida State University | Certain alkoxy substituted taxanes and pharmaceutical compositions containing them |
| IT1254515B (it) * | 1992-03-06 | 1995-09-25 | Indena Spa | Tassani di interesse oncologico, loro metodo di preparazione ed uso |
| US5200534A (en) * | 1992-03-13 | 1993-04-06 | University Of Florida | Process for the preparation of taxol and 10-deacetyltaxol |
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