PL175111B1 - Nowe taksoidy - Google Patents
Nowe taksoidyInfo
- Publication number
- PL175111B1 PL175111B1 PL93324755A PL32475593A PL175111B1 PL 175111 B1 PL175111 B1 PL 175111B1 PL 93324755 A PL93324755 A PL 93324755A PL 32475593 A PL32475593 A PL 32475593A PL 175111 B1 PL175111 B1 PL 175111B1
- Authority
- PL
- Poland
- Prior art keywords
- carbon atoms
- radical
- alkyl
- optionally substituted
- group
- Prior art date
Links
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
- 125000006239 protecting group Chemical group 0.000 claims abstract 4
- -1 alkyl radical Chemical class 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 15
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 150000003254 radicals Chemical class 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 150000001602 bicycloalkyls Chemical group 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical class O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5beta,20-epoxy-1,7beta,13alpha-trihydroxy-9-oxotax-11-ene-2alpha,4alpha,10beta-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)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)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 229930014667 baccatin III Natural products 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- 206010004668 Biliary neoplasm Diseases 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-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
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 241001116500 Taxus Species 0.000 description 1
- 241001116498 Taxus baccata Species 0.000 description 1
- 235000009065 Taxus cuspidata Nutrition 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910001508 alkali metal halide Inorganic materials 0.000 description 1
- 150000008045 alkali metal halides Chemical class 0.000 description 1
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000005227 renal system Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Epoxy Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
1 Nowe taksoidy o ogólnym wzorze I: (I ) w którym G1 oznacza atom wodoru lub grupe acetylowa, alkoksyacetylowa, rodnik alkilowy lub grupe zabezpieczajaca funkcyjna grupe hydroksylowa. PL PL PL PL PL PL PL PL PL
Description
Nowe taksoidy o ogólnym wzorze (III), wykazują działanie wyraźnie hamujące nienormalną proliferację komórkową i posiadają właściwości terapeutyczne pozwalające na leczenie u chorych stanów patologicznych, związanych z nienormalną proliferacją komórkową. Stany patologiczne obejmują nienormalną proliferację komórkową komórek złośliwych lub nie złośliwych różnych tkanek i/lub narządów, włączając w sposób nie ograniczający tkanki mięśniowe, kostne lub łączne, skórę, mózg, płuca, narządy płciowe, układ limfatyczny lub nerkowy, komórki sutkowe lub komórki krwi, wątrobę, narząd trawienny, trzustkę i gruczoły tarczowe lub nadnercza. Stany patologiczne mogą obejmować również łuszczycę, guzy lite, rak jajnika, sutka, mózgu, prostaty, okrężnicy, żołądka, nerek lub jąder, mięsak Kaposiego, nowotwór dróg żółciowych, kosmówczak, nerwiak zarodkowy, guz Wilmsa, ziarnicę złośliwą, czerniaki, szpiczaki mnogie, przewlekłe białaczki limfocytarne, chłoniaki granulocytarne ostre lub przewlekłe. Nowe związki o wzorze (III) są szczególnie przydatne do leczenia raka jajnika.
Produkt o ogólnym wzorze (I) można otrzymać, działając halogenkiem metalu alkalicznego takim jak przykładowo jodek sodu, fluorek potasu, lub azydkiem metalu alkalicznego takim jak przykładowo azydek sodu albo czwartorzędową solą amoniową lub fosforanem metalu alkalicznego, na pochodną bakatyny III lub 10-dezacetylobakatyny III o ogólnym wzorze:
ococ6h5 (II) w którym G1 jest określona jak poprzednio.
Reakcję prowadzi się zazwyczaj w rozpuszczalniku organicznym wybranym spośród eterów takim jak przykładowo tetrahydrofuran, eter dwuizopropylowy, eter III-rz.-butylowo-metylowy i nitryli takich jak przykładowo acetonitryl, pojedynczym lub w mieszaninie w temperaturze od 20°C do temperatury wrzenia mieszaniny reakcyjnej.
Produkt o wzorze (II), w którym Gi oznacza atom wodoru lub grupę acetylową, alkoksyacetylową lub rodnik alkilowy, można otrzymać, działając pochodną kwasu trójfluorometanosulfonowego, taką jak bezwodnik lub N-fenylotrójfluorometanosulfonoimid na bakatynę III lub 10-dezacetyłobakatynę III, które można wyekstrahować znanymi metodami z igieł cisu (Taxus baccata), po czym następuje ewentualnie zabezpieczenie w pozycji 10, przy czym przyjmuje się, że dla otrzymania produktu o ogólnym wzorze (II), w którym. Gi oznacza grupę alkoksyacetylową lub rodnik alkilowy, konieczne jest na wstępie podziałanie na 10-dezacetyłobakatynę III zabezpieczoną w pozycji 7, korzystnie grupą sililową, halogenkiem kwasu alkoksyoctowego lub halogenkiem alkilu.
Reakcję pochodnej kwasu trójfluorometanosulfonowego prowadzi się zwykle w obojętnym rozpuszczalniku organicznym (węglowodory alifatyczne ewentualnie zawierające chlorowiec, węglowodory aromatyczne) w obecności zasady organicznej, takiej jak trzeciorzędowa amina alifatyczna (trójetyloamina) lub pirydyna w temperaturze od -50 do +20°C.
Wprowadzenia grupy alkoksyacetylowej dokonuje się zazwyczaj przez działanie na 10-dezacetyłobakatynę III zabezpieczoną, halogenkiem kwasu alkoksyoctowego w zasadowym rozpuszczalniku organicznym, takim jak pirydyna w temperaturze około 20°C.
Wprowadzenia rodnika alkilowego dokonuje się zwykle, działając na 10-dezacetylobakatynę III zabezpieczoną i z wprowadzonym metalem w pozycji 10 np. za pomocą wodorku alkalicznego (wodorek sodu) lub alkilometalu (butylolit), halogenkiem alkilu.
Niniejszy wynalazek objaśnia następujący przykład.
Przykład. Do roztworu 100 g '10-dezacetylobakatyny III w mieszaninie 2 cm3 tetrahydrofuranu i 0,05 cm3 pirydyny ochłodzonego do temperatury około -78°C i utrzymywanego w atmosferze argonu, wkrapla się 0,09 cm3 bezwodnika trójfluorometanosulfonowego. Pozwala się na powolne dojście do temperatury około 0°C w ciągu około godziny i do około 20°C w ciągu następnej godziny. Po 2 godzinach w temperaturze około 20°C dodaje się 200 mgjodku czterobutyloamoniowego i następnie ogrzewa się roztwór w temperaturze wrzenia rozpuszczalnika w ciągu 15 godzin. Po ochłodzeniu do temperatury około 20°C dodaje się 10 cm3 octanu etylu i potem 1 cm3 wody destylowanej. Po dekantacji fazę organiczną suszy się nad siarczanem magnezu, odsącza i następnie zatęża do sucha pod zmniejszonym ciśnieniem (2,7 kPa) w temperaturze 40°C. Otrzymuje się w ten sposób 116 mg oleju barwy żółtej, który oczyszcza się przez chromatografię pod ciśnieniem atmosferycznym na 30 g krzemionki (0,063 - 0,2 mm), umieszczonej w kolumnie o średnicy 2,5 cm, stosując jako eluent mieszaninę octan etylu-dwuchłorometan z elucją gradientową od 0-100 do 80-20 objętościowo. Frakcje zawierające poszukiwany produkt łączy się i zatęża do sucha pod zmniejszonym ciśnieniem (0,27 kPa) w temperaturze 40°C. Otrzymuje się w ten sposób 10,3 mg 10-dezacetylo-7e,8|S-metyleno-19-norbakatyny III o wzorze I w postaci białej pianki o następującej charakterystyce:
Widmo NMR protonu (400 MHz; CDCh; δ w ppm; stałe sprzężenia J w Hz): 1,14 (s, 3H: -CH3 w 16 lub 17); 1,42 (mt, 1H: -H w 7); 1,76 i 2,31 (t i m, 1H każdy: CH2 z cyklopropanu); 2,07 (s, 3H: -CH3- w 18); 2,15 i 2,50 (d szeroki, i td każdy: -CH2 w 6);
2,30 (s, 3H: -COCH3 w 4); 2,28 i 2,35 (m, 1H każdy: -CH2 w 14); 4,11 i 4,37 (d, 1H każdy: -CH2 w 20); 4,28 (d, 1H: -H w 3); 4,79 (d, 1H: -H w 5); 4,88 (t szeroki, 1H: -H w 13); 5,09 (s, 1H: -Hw 10); 5,66 (d, 1H: -Hw2); 7,51 [t, 2H: -OCOC6H5 (-H w 3 i 5)]; 7,61 [t, 1H: -OCOC6H5 (-H w 4)]; 8 .17 [d, 2H: -OCOCćH (-H w 2 i 6)].
Widmo NMR dla l3C (100 MHz; CDCb; δ w ppm; nie ma sprzężenia; s=singlet; d=dublet; t=triplet; q=kwadruplet): 15 (q, C18); 16,5 (t, C19); 20 i 27 (q, C16 i C17);
22,5 (q, -COCH3); 26,5 (t, C6); 33 (d, C7); 35 (s, C8); 39 (d, C3); 39,5 (t, C14); 43 (s, C15); 68 (d, C13); 76 (t, C20); 76,2 (d, C10); 79,5 (s, C1); 80 (s, C4); 81 (d, C2); 85 (d, C5); 129 (d, C2: -OCOC6H5); 130 (s, Cl z -OCOC6H5); 130,5 (d, C3 z -OCOC6H5); 134 (d, C4 z -OCOC6H5); 136 (s, C11); 143 (s, C12); 168 (s, -OCOC6H5); 171 (s, -COCH3); 210 (s, C9).
Claims (1)
- Nowe taksoidy o ogólnym wzorze I:w którym G1 oznacza atom wodoru lub grupę acetylową, alkoksyacetylową, rodnik alkilowy lub grupę zabezpieczającą funkcyjną grupę hydroksylową.Niniejszy wynalazek dotyczy nowych taksoidów o ogólnym wzorze I:w którym G1 oznacza atom wodoru lub grupę acetylową, alkoksyacetylową, rodnik alkilowy lub grupę zabezpieczającą funkcyjną grupę hydroksylową. Grupę zabezpieczającą może stanowić grupa 2,2,2-trójchloro-etoksykarbonylowa lub 2-(2-trójchlorometylo-propoksy)karbonylowa.Związki o wzorze (I) stanowią nowe związki, które znajdują zastosowanie jako substraty w syntezie nowych taksoidów o ogólnym wzorze III, (III) w którym Ar oznacza rodnik arylowy ewentualnie podstawiony, R oznacza atom wodoru lub grupę acetylową, alkoksyacetylową lub rodnik alkilowy, R1 oznacza grupę175 111 benzoilową lub grupę R2-O-CO-, w której R2 oznacza: rodnik alkilowy o łańcuchu prostym lub rozgałęzionym, zawierający 1 do 8 atomów węgla, alkenylowy, zawierający 2 do 8 atomów węgla, alkinylowy zawierający 3 do 8 atomów węgla, cykloalkilowy, zawierający 3 do 6 atomów węgla, cykloalkenylowy, zawierający 4 do 6 atomów węgla lubbicykloalkilowy, zawierający 7 do 10 atomów węgla, przy czym rodniki te są ewentualnie podstawione jednym lub kilkoma podstawnikami wybranymi spośród atomów chlorowca i grupy hydroksylowej, alkoksylowej, zawierającej 1 do 4 atomów węgla, dwualkiloaminowej, której każda część alkilowa zawiera 1 do 4 atomów węgla, piperydynowej, morfolinowej, 1-piperazynylowej (ewentualnie podstawionej w pozycji 4 rodnikiem alkilowym, zawierającym 1 do 4 atomów węgla lub rodnikiem fenyloakilowym, którego część alkilowa zawiera 1 do 4 atomów węgla), rodnika cykloalkilowego, zawierającego 4 do 6 atomów węgla, fenylowego, grupy cyjanowej, karboksylowej lub alkoksykarbonylowej, której część alkilowa zawiera 1 do 4 atomówwęgla; lub rodnik fenylowy, ewentualnie podstawiony jednym lub kilkoma atomami lub grupami, wybranymi spośród atomów chlorowca i rodników alkilowych, zawierających 1 do 4 atomów węgla, grup alkoksylowych, zawierających 1 do 4 atomów węgla; lub rodnik heterocykliczny, zawierający azot, nasycony lub nienasycony, składający się z 4 lub 6 członów, ewentualnie podstawiony jednym lub kilkoma rodnikami alkilowymi, zawierającymi 1 do 4 atomów węgla, przy czym przyjmuje się, że rodniki cykloalkilowe, cykłoalkenylowe lub bicykloalkilowe można ewentualnie podstawić jednym lub kilkoma rodnikami alkilowymi, zawierającymi 1 do 4 atomów węgla.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9214813A FR2698871B1 (fr) | 1992-12-09 | 1992-12-09 | Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| PCT/FR1993/001201 WO1994013654A1 (fr) | 1992-12-09 | 1993-12-07 | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL175111B1 true PL175111B1 (pl) | 1998-11-30 |
Family
ID=9436375
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL93309293A PL174830B1 (pl) | 1992-12-09 | 1993-12-07 | Nowe taksoidy, ich wytwarzanie i zawierające je kompozycje farmaceutyczne |
| PL93324755A PL175111B1 (pl) | 1992-12-09 | 1993-12-07 | Nowe taksoidy |
| PL93324756A PL175539B1 (pl) | 1992-12-09 | 1993-12-07 | Nowe taksoidy |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL93309293A PL174830B1 (pl) | 1992-12-09 | 1993-12-07 | Nowe taksoidy, ich wytwarzanie i zawierające je kompozycje farmaceutyczne |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL93324756A PL175539B1 (pl) | 1992-12-09 | 1993-12-07 | Nowe taksoidy |
Country Status (30)
| Country | Link |
|---|---|
| US (9) | US7074821B1 (pl) |
| EP (1) | EP0673372B1 (pl) |
| JP (2) | JP2785248B2 (pl) |
| KR (1) | KR100346328B1 (pl) |
| CN (1) | CN1055467C (pl) |
| AT (1) | ATE243688T1 (pl) |
| AU (2) | AU685415B2 (pl) |
| BG (1) | BG61726B1 (pl) |
| BR (1) | BR9307613A (pl) |
| CA (1) | CA2150944C (pl) |
| CZ (1) | CZ289851B6 (pl) |
| DE (1) | DE69333064T2 (pl) |
| DK (1) | DK0673372T3 (pl) |
| ES (1) | ES2202319T3 (pl) |
| FI (1) | FI110941B (pl) |
| FR (1) | FR2698871B1 (pl) |
| HU (1) | HU227872B1 (pl) |
| MX (1) | MX9307748A (pl) |
| NO (1) | NO310555B1 (pl) |
| NZ (1) | NZ258592A (pl) |
| OA (1) | OA10166A (pl) |
| PL (3) | PL174830B1 (pl) |
| PT (1) | PT673372E (pl) |
| RO (1) | RO112281B1 (pl) |
| RU (1) | RU2139864C1 (pl) |
| SG (1) | SG67338A1 (pl) |
| SK (1) | SK282139B6 (pl) |
| TW (1) | TW408120B (pl) |
| UA (1) | UA51612C2 (pl) |
| WO (1) | WO1994013654A1 (pl) |
Families Citing this family (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2696460B1 (fr) * | 1992-10-05 | 1994-11-25 | Rhone Poulenc Rorer Sa | Procédé de préparation de dérivés du taxane. |
| FR2697752B1 (fr) | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Compositions antitumorales contenant des dérivés du taxane. |
| FR2698361B1 (fr) * | 1992-11-20 | 1995-01-13 | Rhone Poulenc Rorer Sa | Procédé de préparation d'un acide oxazolidine-1,3 carboxylique-5. |
| FR2698871B1 (fr) * | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| US5814658A (en) * | 1992-12-09 | 1998-09-29 | Rhone-Poulenc Rorer S.A. | Taxoids, their preparation and pharmaceutical compositions containing them |
| MX9307777A (es) | 1992-12-15 | 1994-07-29 | Upjohn Co | 7-HALO-Y 7ß, 8ß-METANO-TAXOLES, USO ANTINEOPLASTICO Y COMPOSICIONES FARMACEUTICAS QUE LOS CONTIENEN. |
| US5973160A (en) * | 1992-12-23 | 1999-10-26 | Poss; Michael A. | Methods for the preparation of novel sidechain-bearing taxanes |
| EP0982301B1 (en) * | 1993-06-11 | 2003-09-10 | PHARMACIA & UPJOHN COMPANY | Delta 6,7-taxols antineoplastic use and pharmaceutical compositions containing them |
| FR2706457B1 (fr) * | 1993-06-16 | 1995-07-28 | Rhone Poulenc Rorer Sa | Procédé de préparation d'un acide oxazolidinecarboxylique utile pour préparer des taxoïdes thérapeutiquement actifs. |
| FR2712288B1 (fr) * | 1993-11-08 | 1996-01-05 | Rhone Poulenc Rorer Sa | Nouveaux taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| IL127599A (en) * | 1994-01-28 | 2004-06-01 | Upjohn Co | Process for preparing isotaxol analogs |
| FR2721023B1 (fr) * | 1994-06-09 | 1996-07-12 | Rhone Poulenc Rorer Sa | Nouveaux Taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| FR2721024B1 (fr) * | 1994-06-09 | 1996-07-12 | Rhone Poulenc Rorer Sa | Nouveaux taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| FR2726272B1 (fr) * | 1994-10-26 | 1996-12-06 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
| CA2170661A1 (en) * | 1995-03-22 | 1996-09-23 | John K. Thottathil | Novel methods for the preparation of taxanes using oaxzolidine intermediates |
| FR2732342B1 (fr) * | 1995-04-03 | 1997-04-30 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2732968B1 (fr) * | 1995-04-14 | 1997-05-16 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2742438B1 (fr) * | 1995-12-14 | 1998-01-16 | Rhone Poulenc Rorer Sa | Dihydrate du (2r,3s)-3-tert-butoxycarbonylamino-2-hydroxy- 3-phenylpropionate de 4,10beta-diacetoxy-2alpha-benzoyloxy- 5beta,2o-epoxy-1-hydroxy-9-oxo-19-nor-cyclopropa(g)tax-11- ene-13alpha-yle, et son procede de preparation |
| FR2742357B1 (fr) * | 1995-12-19 | 1998-01-09 | Rhone Poulenc Rorer Sa | Nanoparticules stabilisees et filtrables dans des conditions steriles |
| FR2742753B1 (fr) * | 1995-12-22 | 1998-01-30 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
| US5919815A (en) * | 1996-05-22 | 1999-07-06 | Neuromedica, Inc. | Taxane compounds and compositions |
| US5795909A (en) | 1996-05-22 | 1998-08-18 | Neuromedica, Inc. | DHA-pharmaceutical agent conjugates of taxanes |
| ES2151277T3 (es) * | 1996-05-22 | 2000-12-16 | Protarga Inc | Composiciones que comprenden conjugados de acido cis-docosahexaenoico y taxotere. |
| WO1997045105A1 (en) | 1996-05-24 | 1997-12-04 | Angiotech Pharmaceuticals, Inc. | Compositions and methods for treating or preventing diseases of body passageways |
| FR2750989B1 (fr) * | 1996-07-09 | 1998-09-25 | Rhone Poulenc Rorer Sa | Procede de monoacylation d'hydroxy taxanes |
| US5773464A (en) * | 1996-09-30 | 1998-06-30 | Bristol-Myers Squibb Company | C-10 epoxy taxanes |
| WO1998017656A1 (en) | 1996-10-24 | 1998-04-30 | Institute Armand-Frappier | A family of canadensol taxanes, the semi-synthetic preparation and therapeutic use thereof |
| US20030157187A1 (en) * | 1996-12-02 | 2003-08-21 | Angiotech Pharmaceuticals, Inc. | Compositions and methods for treating or preventing inflammatory diseases |
| US6495579B1 (en) | 1996-12-02 | 2002-12-17 | Angiotech Pharmaceuticals, Inc. | Method for treating multiple sclerosis |
| US6515016B2 (en) | 1996-12-02 | 2003-02-04 | Angiotech Pharmaceuticals, Inc. | Composition and methods of paclitaxel for treating psoriasis |
| JP2001523103A (ja) * | 1997-04-28 | 2001-11-20 | ローヌ−プーラン・ロレ・エス・アー | 腫瘍治療用血管形成アンタゴニストのアデノウイルスによる腫瘍内送達 |
| US7288665B1 (en) * | 1997-08-18 | 2007-10-30 | Florida State University | Process for selective derivatization of taxanes |
| ATE234800T1 (de) | 1997-08-21 | 2003-04-15 | Univ Florida State | Verfahren zur synthese von taxanen |
| US6831057B2 (en) * | 1997-10-28 | 2004-12-14 | The University Of North Carolina At Chapel Hill | Use of NF-κB inhibition in combination therapy for cancer |
| US6150537A (en) * | 1997-12-12 | 2000-11-21 | Emory University | Methods for the esterification of alcohols and compounds useful therefor as potential anticancer agents |
| ATE219070T1 (de) * | 1998-01-14 | 2002-06-15 | Bristol Myers Squibb Co | Neue kristallkomplexe von baccatin iii mit imidazol, 2-methylimidazol or isopropanol |
| US6156789A (en) * | 1998-03-17 | 2000-12-05 | Rhone-Poulenc Rorer S.A. | Method for treating abnormal cell proliferation in the brain |
| US6391911B1 (en) * | 1999-02-26 | 2002-05-21 | Robert E. Bases | Coadministration of lucanthone and radiation for treatment of cancer |
| US7235583B1 (en) | 1999-03-09 | 2007-06-26 | Luitpold Pharmaceuticals, Inc., | Fatty acid-anticancer conjugates and uses thereof |
| EP1176957A1 (en) * | 1999-05-03 | 2002-02-06 | Aventis Pharma S.A. | Method for treating abnormal cell proliferation in the brain |
| FR2794771B1 (fr) * | 1999-06-11 | 2001-08-10 | Aventis Pharma Sa | Adenovirus recombinants codant pour le transporteur specifique de l'iode (nis) |
| HK1049787B (en) | 1999-10-01 | 2014-07-25 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| AU774787B2 (en) * | 1999-10-15 | 2004-07-08 | Daiichi Sankyo Company, Limited | Pentacyclic taxane compounds |
| US6750246B1 (en) * | 2000-02-03 | 2004-06-15 | Bristol-Myers Squibb Company | C-4 carbonate taxanes |
| AU7007001A (en) | 2000-06-22 | 2002-01-02 | Nitromed Inc | Nitrosated and nitrosylated taxanes, compositions and methods of use |
| AU2001288805A1 (en) * | 2000-09-22 | 2002-04-02 | Bristol-Myers Squibb Company | Method for reducing toxicity of combined chemotherapies |
| WO2004033442A2 (en) * | 2002-10-09 | 2004-04-22 | Chatham Biotec Ltd. | Novel taxanes and methods related to use and preparation thereof |
| US7787855B2 (en) * | 2003-03-31 | 2010-08-31 | Motorola, Inc. | Establishing emergency sessions in packet data networks for wireless devices having invalid subscriber identities |
| FR2853651B1 (fr) * | 2003-04-14 | 2005-05-20 | Aventis Pharma Sa | Procede de preparation du 4,10 beta-diacetoxy-2 alpha- benzoyloxy-5 beta, 20-epoxy-1, 13 alpha-dihydroxy-9-oxo-19- norcyclopropa[g]tax-11-ene |
| US6956124B2 (en) | 2003-04-14 | 2005-10-18 | Aventis Pharma S.A. | Process for the preparation of 4,10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1,13α-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene |
| US7202370B2 (en) * | 2003-10-27 | 2007-04-10 | Conor Medsystems, Inc. | Semi-synthesis of taxane intermediates from 9-dihydro-13-acetylbaccatin III |
| EP2371416B1 (en) * | 2005-11-18 | 2018-08-22 | Respicardia, Inc. | System to modulate phrenic nerve to prevent sleep apnea |
| CN100516067C (zh) * | 2006-01-10 | 2009-07-22 | 上海恒瑞医药有限公司 | 具有抗肿瘤活性的紫杉酚衍生物 |
| JP2009533330A (ja) * | 2006-03-21 | 2009-09-17 | ドクター レディズ ラボラトリーズ リミテッド | ドセタキセルの多形体およびプロセス |
| CN100588643C (zh) * | 2006-11-02 | 2010-02-10 | 南京航空航天大学 | 一种含有二取代金刚烷基的维甲酸类化合物制备方法 |
| US20090076127A1 (en) * | 2007-09-19 | 2009-03-19 | Protia, Llc | Deuterium-enriched larotaxel |
| CN101863861A (zh) * | 2009-04-16 | 2010-10-20 | 山东靶点药物研究有限公司 | 一种简便高效地制备紫杉醇类似物Larotaxel的方法 |
| KR101712231B1 (ko) | 2009-10-29 | 2017-03-03 | 아벤티스 파마 소시에떼아노님 | 카바지탁셀의 신규한 항종양 용도 |
| SG185389A1 (en) | 2010-05-03 | 2012-12-28 | Teikoku Pharma Usa Inc | Non-aqueous taxane pro-emulsion formulations and methods of making and using the same |
| LT2753355T (lt) | 2011-09-08 | 2019-01-25 | New York University | Onkolitinis herpes simplex virusas ir jo terapinis panaudojimas |
| US9745631B2 (en) | 2011-12-20 | 2017-08-29 | Dana-Farber Cancer Institute, Inc. | Methods for diagnosing and treating oncogenic kras-associated cancer |
| WO2013177426A2 (en) | 2012-05-24 | 2013-11-28 | Dana-Farber Cancer Institute, Inc. | Targeting the glutamine to pyruvate pathway for treatment of oncogenic kras-associated cancer |
| US20150285802A1 (en) | 2012-07-18 | 2015-10-08 | Dana-Farber Cancer Institute, Inc. | Methods for treating, preventing and predicting risk of developing breast cancer |
| JO3685B1 (ar) | 2012-10-01 | 2020-08-27 | Teikoku Pharma Usa Inc | صيغ التشتيت الجسيمي للتاكسين غير المائي وطرق استخدامها |
| WO2014149871A1 (en) | 2013-03-14 | 2014-09-25 | Icahn School Of Medicine At Mount Sinai | Autologous tumor lysate-loaded dendritic cell vaccine for treatment of liver cancer |
| WO2015050844A1 (en) | 2013-10-01 | 2015-04-09 | Dana-Farber Cancer Institute, Inc. | Methods of treating cancer with atovaquone-related compounds |
| US10350264B2 (en) | 2014-03-27 | 2019-07-16 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for modulating NCOA4-mediated autophagic targeting of ferritin |
| MA39818A (fr) | 2014-03-30 | 2017-02-08 | Benevir Biopharm Inc | Virus oncolytiques « armés » comprenant un inhibiteur de tap exogène et leurs utilisations thérapeutiques |
| EP3307330B1 (en) | 2015-06-15 | 2021-03-10 | New York University | Method of treatment using oncolytic viruses |
| CN112574134A (zh) * | 2020-12-30 | 2021-03-30 | 重庆市碚圣医药科技股份有限公司 | 一种多西紫杉醇侧链的合成方法 |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US487399A (en) * | 1892-12-06 | Timepiece repeating mechanism | ||
| US4534899A (en) | 1981-07-20 | 1985-08-13 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
| US4507217A (en) | 1983-03-07 | 1985-03-26 | Lipid Specialties, Inc. | Magnetic compositions and magnetic memory devices prepared therefrom |
| FR2601675B1 (fr) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2601676B1 (fr) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Procede de preparation du taxol et du desacetyl-10 taxol |
| US4876399A (en) * | 1987-11-02 | 1989-10-24 | Research Corporation Technologies, Inc. | Taxols, their preparation and intermediates thereof |
| GB8806224D0 (en) | 1988-03-16 | 1988-04-13 | Johnson Matthey Plc | Platinum chemotherapeutic product |
| FR2629819B1 (fr) | 1988-04-06 | 1990-11-16 | Rhone Poulenc Sante | Procede de preparation de derives de la baccatine iii et de la desacetyl-10 baccatine iii |
| US4960790A (en) * | 1989-03-09 | 1990-10-02 | University Of Kansas | Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof |
| MY110249A (en) | 1989-05-31 | 1998-03-31 | Univ Florida State | Method for preparation of taxol using beta lactam |
| US5175315A (en) * | 1989-05-31 | 1992-12-29 | Florida State University | Method for preparation of taxol using β-lactam |
| US5411947A (en) | 1989-06-28 | 1995-05-02 | Vestar, Inc. | Method of converting a drug to an orally available form by covalently bonding a lipid to the drug |
| US5015744A (en) | 1989-11-14 | 1991-05-14 | Florida State University | Method for preparation of taxol using an oxazinone |
| US5136060A (en) | 1989-11-14 | 1992-08-04 | Florida State University | Method for preparation of taxol using an oxazinone |
| MX9102128A (es) | 1990-11-23 | 1992-07-08 | Rhone Poulenc Rorer Sa | Derivados de taxano,procedimiento para su preparacion y composicion farmaceutica que los contiene |
| US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
| WO1992019765A1 (en) | 1991-05-08 | 1992-11-12 | The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Method for designing cancer treatment regimens and methods and pharmaceutical compositions for the treatment of cancer |
| US5645988A (en) | 1991-05-08 | 1997-07-08 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of identifying drugs with selective effects against cancer cells |
| US5698582A (en) | 1991-07-08 | 1997-12-16 | Rhone-Poulenc Rorer S.A. | Compositions containing taxane derivatives |
| US5489601A (en) | 1991-09-23 | 1996-02-06 | Florida State University | Taxanes having a pyridyl substituted side-chain and pharmaceutical compositions containing them |
| US5284864A (en) | 1991-09-23 | 1994-02-08 | Florida State University | Butenyl substituted taxanes and pharmaceutical compositions containing them |
| US5274124A (en) | 1991-09-23 | 1993-12-28 | Florida State University | Metal alkoxides |
| SG46582A1 (en) | 1991-09-23 | 1998-02-20 | Univ Florida State | 10-Desacetoxytaxol derivatives |
| US5714513A (en) | 1991-09-23 | 1998-02-03 | Florida State University | C10 taxane derivatives and pharmaceutical compositions |
| US5739362A (en) | 1991-09-23 | 1998-04-14 | Florida State University | Taxanes having an alkoxy, alkenoxy or aryloxy substituted side-chain and pharmaceutical compositions containing them |
| US5338872A (en) | 1993-01-15 | 1994-08-16 | Florida State University | Process for the preparation of 10-desacetoxybaccatin III and 10-desacetoxytaxol and derivatives thereof |
| US5283253A (en) | 1991-09-23 | 1994-02-01 | Florida State University | Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them |
| US5229526A (en) | 1991-09-23 | 1993-07-20 | Florida State University | Metal alkoxides |
| US5399726A (en) | 1993-01-29 | 1995-03-21 | Florida State University | Process for the preparation of baccatin III analogs bearing new C2 and C4 functional groups |
| US5728850A (en) | 1991-09-23 | 1998-03-17 | Florida State University | Taxanes having a butenyl substituted side-chain 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 |
| US5710287A (en) | 1991-09-23 | 1998-01-20 | Florida State University | Taxanes having an amino substituted side-chain and pharmaceutical compositions containing them |
| US5430160A (en) | 1991-09-23 | 1995-07-04 | Florida State University | Preparation of substituted isoserine esters using β-lactams and metal or ammonium alkoxides |
| US5243045A (en) | 1991-09-23 | 1993-09-07 | Florida State University | Certain alkoxy substituted taxanes and pharmaceutical compositions containing them |
| US5721268A (en) | 1991-09-23 | 1998-02-24 | Florida State University | C7 taxane derivatives and pharmaceutical compositions containing them |
| US5728725A (en) | 1991-09-23 | 1998-03-17 | Florida State University | C2 taxane derivaties and pharmaceutical compositions containing them |
| US5654447A (en) | 1991-09-23 | 1997-08-05 | Florida State University | Process for the preparation of 10-desacetoxybaccatin III |
| US5250683A (en) | 1991-09-23 | 1993-10-05 | Florida State University | Certain substituted taxanes and pharmaceutical compositions containing them |
| US5262409A (en) | 1991-10-11 | 1993-11-16 | Fred Hutchinson Cancer Research Center | Binary tumor therapy |
| US5294737A (en) | 1992-02-27 | 1994-03-15 | The Research Foundation State University Of New York | Process for the production of chiral hydroxy-β-lactams and hydroxyamino acids derived therefrom |
| DE69329073T2 (de) | 1992-03-23 | 2001-01-18 | Georgetown University, Washington | In liposomen verkapseltes taxol und verwendungsverfahren |
| US5254703A (en) | 1992-04-06 | 1993-10-19 | Florida State University | Semi-synthesis of taxane derivatives using metal alkoxides and oxazinones |
| US5294637A (en) | 1992-07-01 | 1994-03-15 | Bristol-Myers Squibb Company | Fluoro taxols |
| US5254580A (en) | 1993-01-19 | 1993-10-19 | Bristol-Myers Squibb Company | 7,8-cyclopropataxanes |
| US5319112A (en) | 1992-08-18 | 1994-06-07 | Virgnia Tech Intellectual Properties, Inc. | Method for the conversion of cephalomannine to taxol and for the preparation of N-acyl analogs of taxol |
| FR2696459B1 (fr) | 1992-10-05 | 1994-11-25 | Rhone Poulenc Rorer Sa | Procédé de préparation de dérivés du taxane. |
| FR2697752B1 (fr) | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Compositions antitumorales contenant des dérivés du taxane. |
| US5814658A (en) | 1992-12-09 | 1998-09-29 | Rhone-Poulenc Rorer S.A. | Taxoids, their preparation and pharmaceutical compositions containing them |
| FR2698871B1 (fr) | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| MX9307777A (es) | 1992-12-15 | 1994-07-29 | Upjohn Co | 7-HALO-Y 7ß, 8ß-METANO-TAXOLES, USO ANTINEOPLASTICO Y COMPOSICIONES FARMACEUTICAS QUE LOS CONTIENEN. |
| CA2111527C (en) | 1992-12-24 | 2000-07-18 | Jerzy Golik | Phosphonooxymethyl ethers of taxane derivatives |
| ZA94128B (en) | 1993-02-01 | 1994-08-19 | Univ New York State Res Found | Process for the preparation of taxane derivatives and betalactam intermediates therefor |
| FR2703049B1 (fr) | 1993-03-22 | 1995-04-21 | Rhone Poulenc Rorer Sa | Procédé de purification des taxoïdes. |
| AU6833994A (en) | 1993-05-17 | 1994-12-12 | Liposome Company, Inc., The | Incorporation of taxol into liposomes and gels |
| AU6832794A (en) | 1993-05-19 | 1994-12-12 | Liposome Company, Inc., The | Liposome having a multicomponent bilayer which contains a bioactive agent as an integral component of the bilayer |
| US5405972A (en) | 1993-07-20 | 1995-04-11 | Florida State University | Synthetic process for the preparation of taxol and other tricyclic and tetracyclic taxanes |
| CA2129288C (en) | 1993-08-17 | 2000-05-16 | Jerzy Golik | Phosphonooxymethyl esters of taxane derivatives |
| US6441026B1 (en) | 1993-11-08 | 2002-08-27 | Aventis Pharma S.A. | Antitumor compositions containing taxane derivatives |
| FR2712288B1 (fr) * | 1993-11-08 | 1996-01-05 | Rhone Poulenc Rorer Sa | Nouveaux taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| US5415869A (en) | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
| FR2718963B1 (fr) | 1994-04-25 | 1996-05-24 | Rhone Poulenc Rorer Sa | Nouvelle composition pharmaceutique à base de taxoïdes. |
| DE69504843T2 (de) | 1994-06-28 | 1999-02-11 | Pharmacia & Upjohn Co., Kalamazoo, Mich. | 7-äther-taxol ähnliche verbindungen antineoplastische verwendung und diese enthaltende pharmazeutische zusammenstellungen |
| FR2721928A1 (fr) | 1994-07-04 | 1996-01-05 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
| US6201140B1 (en) | 1994-07-28 | 2001-03-13 | Bristol-Myers Squibb Company | 7-0-ethers of taxane derivatives |
| FR2726272B1 (fr) | 1994-10-26 | 1996-12-06 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
| US5635531A (en) | 1996-07-08 | 1997-06-03 | Bristol-Myers Squibb Company | 3'-aminocarbonyloxy paclitaxels |
| US6156789A (en) | 1998-03-17 | 2000-12-05 | Rhone-Poulenc Rorer S.A. | Method for treating abnormal cell proliferation in the brain |
| EP0982028A1 (en) | 1998-08-20 | 2000-03-01 | Aventis Pharma S.A. | New use of taxoid derivatives |
-
1992
- 1992-12-09 FR FR9214813A patent/FR2698871B1/fr not_active Expired - Lifetime
-
1993
- 1993-07-12 UA UA95062617A patent/UA51612C2/uk unknown
- 1993-12-07 ES ES94901993T patent/ES2202319T3/es not_active Expired - Lifetime
- 1993-12-07 AU AU56531/94A patent/AU685415B2/en not_active Expired
- 1993-12-07 RO RO95-01107A patent/RO112281B1/ro unknown
- 1993-12-07 SG SG1996007594A patent/SG67338A1/en unknown
- 1993-12-07 DE DE69333064T patent/DE69333064T2/de not_active Expired - Lifetime
- 1993-12-07 PL PL93309293A patent/PL174830B1/pl unknown
- 1993-12-07 CZ CZ19951455A patent/CZ289851B6/cs not_active IP Right Cessation
- 1993-12-07 WO PCT/FR1993/001201 patent/WO1994013654A1/fr not_active Ceased
- 1993-12-07 JP JP6513859A patent/JP2785248B2/ja not_active Expired - Fee Related
- 1993-12-07 NZ NZ258592A patent/NZ258592A/en not_active IP Right Cessation
- 1993-12-07 AT AT94901993T patent/ATE243688T1/de active
- 1993-12-07 HU HU9501662A patent/HU227872B1/hu not_active IP Right Cessation
- 1993-12-07 BR BR9307613A patent/BR9307613A/pt not_active Application Discontinuation
- 1993-12-07 PL PL93324755A patent/PL175111B1/pl unknown
- 1993-12-07 EP EP94901993A patent/EP0673372B1/fr not_active Expired - Lifetime
- 1993-12-07 RU RU95114534A patent/RU2139864C1/ru not_active IP Right Cessation
- 1993-12-07 SK SK752-95A patent/SK282139B6/sk not_active IP Right Cessation
- 1993-12-07 DK DK94901993T patent/DK0673372T3/da active
- 1993-12-07 PT PT94901993T patent/PT673372E/pt unknown
- 1993-12-07 CA CA002150944A patent/CA2150944C/fr not_active Expired - Fee Related
- 1993-12-07 KR KR1019950702380A patent/KR100346328B1/ko not_active Expired - Lifetime
- 1993-12-07 PL PL93324756A patent/PL175539B1/pl unknown
- 1993-12-08 TW TW082110390A patent/TW408120B/zh not_active IP Right Cessation
- 1993-12-08 MX MX9307748A patent/MX9307748A/es unknown
- 1993-12-08 US US08/162,984 patent/US7074821B1/en not_active Expired - Fee Related
- 1993-12-09 CN CN93121690A patent/CN1055467C/zh not_active Expired - Fee Related
-
1995
- 1995-06-07 US US08/479,199 patent/US5580998A/en not_active Expired - Lifetime
- 1995-06-07 US US08/474,417 patent/US5571917A/en not_active Expired - Lifetime
- 1995-06-07 US US08/475,621 patent/US5532388A/en not_active Expired - Fee Related
- 1995-06-07 US US08/483,697 patent/US5599942A/en not_active Expired - Lifetime
- 1995-06-07 US US08/474,551 patent/US5576450A/en not_active Expired - Fee Related
- 1995-06-07 US US08/487,232 patent/US5587493A/en not_active Expired - Lifetime
- 1995-06-07 US US08/479,198 patent/US5580997A/en not_active Expired - Fee Related
- 1995-06-07 US US08/483,693 patent/US5550261A/en not_active Expired - Lifetime
- 1995-06-08 NO NO19952264A patent/NO310555B1/no not_active IP Right Cessation
- 1995-06-08 FI FI952825A patent/FI110941B/fi not_active IP Right Cessation
- 1995-06-09 BG BG99713A patent/BG61726B1/bg unknown
- 1995-06-09 OA OA60675A patent/OA10166A/fr unknown
-
1997
- 1997-10-16 AU AU41870/97A patent/AU704663B2/en not_active Expired
-
1998
- 1998-02-19 JP JP10052669A patent/JPH10291930A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PL175111B1 (pl) | Nowe taksoidy | |
| SK281035B6 (sk) | Spôsob prípravy esterov baccatínu iii alebo 10-desacetylbaccatínu iii, ester baccatínu iii alebo 10-desacetylbaccatínu iii a medziprodukt na uvedený spôsob | |
| CS263291A3 (en) | Taxol water-soluble derivatives | |
| PL179147B1 (pl) | Sposób wytwarzania pochodnych taksanu PL PL PL PL PL PL PL | |
| SK280627B6 (sk) | Spôsob prípravy derivátov taxánu a medziprodukty n | |
| EA000709B1 (ru) | Таксоиды, способы их получения и фармацевтическая композиция на их основе и промежуточные соединения | |
| EA001533B1 (ru) | Новые таксоиды, их получение и содержащие их фармацевтические композиции | |
| RU2009105669A (ru) | Способ получения 3-замещенных 2-амино-5-галогенбензамидов | |
| MXPA06000951A (es) | Sintesis regioselectiva de cci-779. | |
| US5449790A (en) | Preparation of 10-deacetylbaccatin III and 7-protected-10-deacetylbaccatin III derivatives from 10-deacetyl taxol A, 10-deacetyl taxol B, and 10-deacetyl taxol C | |
| AU683560B2 (en) | Process for preparing 7-trialkylsilyl baccatin III | |
| US7186851B2 (en) | Facile method for synthesizing baccatin III compounds | |
| JP2010516790A (ja) | 新規なビンブラスチン誘導体、その調製方法と用途、及び該誘導体を含む医薬組成物 | |
| US5907042A (en) | Intermediates and methods useful in the semisynthesis of paclitaxel and analogs | |
| Hartung et al. | Selectivity of N-versus O-alkylation in mitsunobu reactions with various quinolinols and isoquinolinols | |
| JP3423002B2 (ja) | タキサン誘導体、その調製、及びそれを含有する処方物 | |
| CZ125797A3 (en) | Novel taxoids, process of their preparation and pharmaceutical composition containing thereof | |
| Lin et al. | Metal-free synthesis of 5-trifluoromethyltetrazoles | |
| Liu et al. | Synthesis and antiproliferative activity of pterostilbene and 3′-methoxy pterostilbene Mannich base derivatives against Hela cells | |
| US6017935A (en) | 7-sulfur substituted paclitaxels | |
| Palacios et al. | Synthesis of novel 2, 5-dihydro-1, 5, 2-diazaphosphinines from primary enamine phosphonates and from alkyl phosphonates | |
| CN110511197B (zh) | 一种n-呋喃酮基芳基磺酰腙类化合物及其合成方法和应用 | |
| Yong et al. | New Ferrocene Formates Bearing Isoxazole Moieties: Synthesis, Characterization, X-ray Crystallography, and Preliminarily Cytotoxicity against A549, HCT116, and MCF-7 Cell Lines | |
| Yokomatsu et al. | 1, 3-Dipolar Cycloaddition of Diazomethane to 1, 1-Difluoroallyi-phosphonates: Application to Synthesis of Cyclopropane Derivatives Having a Diethoxyphosphoryldifluoromethylene Unit | |
| PL173791B1 (pl) | Sposób wytwarzania pochodnych taksanu |