90 results about "Taxane derivative" patented technology

The present invention concerns novel taxane derivatives, their use as antitumor agents, and pharmaceutical formulations.The invention claims compounds of formula I and the use of compounds of formula I or pharmaceutical salts thereof as oral drugs for the treatment of human or veterinary disease.in which:R is phenyl, isopropyl, or tert butyl;R<1 >is -C(O)R<z >in which R<z >is (CH3)3CO-, (CH3)3CCH2-, CH3(CH2)3O-, cyclobutyl-, cyclohexyloxy, or (2-furyl);R<2 >is CH3C(O)O-.

Pharmaceutical compositions for oral administration to mammalian subjects comprise a taxane or taxane derivative (e.g., paclitaxel or docetaxel) as active ingredient and a vehicle comprising at least 30% by weight of a carrier for the taxane, said carrier having an HLB value of at least about 10. The compositions may also comprise 0–70% of a viscosity-reducing co-solubilizer. The compositions may be incorporated into conventional oral pharmaceutical dosage forms, or can be in the form of a two-part medicament wherein the first part includes the taxane in a solubilizing vehicle and the second part comprises a carrier for the taxane to promote oral absorption. Methods of treatment of taxane-responsive disease conditions employing the novel compositions are also disclosed, whereby the compositions can be administered alone or in association with an oral bioavailability enhancing agent.

[Problems] To provide a novel taxane derivative which can release the medicinal substance in a bioenzyme-independent manner, is expected to have an effective therapeutic efficacy, and has a water-solubility.[Means for Solving Problems] Disclosed is a polymer conjugate of a taxane, which comprises a polymer having a polyethylene glycol moiety and two or more succinic acid monoamide moieties and a taxane, wherein a carboxylate group in the polymer and an alcoholic hydroxyl group in the taxane are bound to each other via an ester bonding.

The present invention relates to a methods of preparing active compounds complexed with lipids using aqueous systems that are free of organic solvents, and methods of using the complexes, e.g., in treating a disease in a subject. In some embodiments, the present invention comprises a composition comprising a complex comprising at least one active compound, e.g., a polyene antibiotic, an immunosuppressant agent such as tacrolimus or a taxane or taxane derivative, and one or more lipids. In some embodiments, the present invention provides a method comprising preparing a composition comprising a lipid complex comprising at least one active compound and at least one lipid and administering the composition to a subject. In certain embodiments the subject is a mammal. In certain preferred embodiments, the subject is human.

The invention provides a new taxane derivative and a preparation method thereof as well as a method of preparing antitumor medicaments (cabazitaxel, docetaxel and taxol) by utilizing new taxane isoserine ester.

A process is provided for the semi-synthesis of taxane intermediates useful in the preparation of paclitaxel and docetaxel, in particular, the semi-synthesis of protected taxane intermediate in a one pot reaction of protecting the C-7, 10 and attaching a side chain at C-13 position and subsequently deprotecting the group to form paclitaxel or docetaxel, and intermediates used therein.

The present invention relates to a lyophilized pharmaceutical composition for injection having superior storage stability comprising a taxoid, and a method thereof. More specifically, the present invention relates to a lyophilized pharmaceutical composition for injection having improved solubility and stability of dilution compared to the conventional preparations by dissolving a water-insoluble taxoid in distilled water added with a hydrophilic polymer such as hydroxypropylmethyl cellulose (HPMC), polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP) cyclodextrin (CD), and lyophilizing the mixture and a method thereof.

Disclosed are pharmaceutical compositions which comprise an orally-active taxane derivative and a pharmaceutically acceptable solubilizing agent, and which provide effective and consistent oral absorption of the taxane derivative.

An object of the invention is to develop galactose or mannose derivatives of docetaxel, etc. having improved solubility and physiological activity, to alleviate burden imposed on patients and to provide effective therapeutic drug for tumors.The present invention provides taxoid derivatives comprising any of paclitaxel, docetaxel and 10-deacetyl-baccatin III to which galactose or mannose is linked through a spacer, and methods for producing taxoid derivatives comprising reacting paclitaxel, docetaxel or 10-deacetyl-baccatin III with tetrabenzyl acetyloxygalactoside or tetrabenzyl acetyloxymannoside, subjecting the product to debenzylation reaction, and optionally to detriethylsilylation reaction.

The present invention concerns novel 7-deoxy taxane derivatives their use as antitumor agents, and pharmaceutical formulations.

The invention relates to an improved process for the synthesis of 13-(N-Boc-β-isobutylserinyl)-14-β-hydroxybaccatin III-1,14-carbonate (I), wherein carbonation of the 1,14-hydroxy groups of the baccatin skeleton is carried out with bis(trichloromethylcarbonate and the 7-hydroxy group is protected with a trichloroacetyl group.

Multiple myeloma and other hematologic tumors and / or malignancies can be treated by administration of a G1 and / or S phase drug, which is preferably β-lapachone, or a derivative or analog thereof, combined with a G2 / M phase drug such as a taxane derivative, which is advantageously paclitaxel. This combination of the G1 and / or S phase drug with the G2 / M phase drug results in an unexpectedly greater than additive (i.e., synergistic) apoptosis in multiple myeloma cells. The invention includes methods of treating multiple myeloma by administering the combination of the G1 and / or S phase drug and the G2 / M phase drug, pharmaceutical compositions comprising the combination of drugs used in these methods, as well as pharmaceutical kits.

This invention relates a method of treating hyperproliferative diseases. More particularly, the present invention relates to a method of treating hyperproliferative diseases, such as cancer, comprising the step of administering to a mammal in need of such treatment, either simultaneously or sequentially, (i) a therapeutically effective amount of a taxane derivative, a platinium coordination complex selected from the group consisting of carboplatin, tetraplatin, and topotecan, a nucleoside analog selected from the group consisting of gemcitabine hydrochloride and 5-FU, an anthracycline, a topoisomerase selected from the group consisting of etoposide, teniposide, amsacrine, topotecan, and Camptosar®, an aromatase inhibitor; and (ii) a therapeutically effective amount of an isothiazole derivative. The combinations of the present invention may optionally include an anti-hypertensive agent. This invention also relates to pharmaceutical compositions useful in the treatment of hyperproliferative diseases in mammals, containing such combinations. The present invention also relates to kits having a first compartment with a compound of formula 1 and a second compartment containing a taxane derivative, a platinum coordination complex, a nucleoside analog, an anthracycline, a topoisomerase inhibitor, or an aromatase inhibitor and a third compartment containing an anti-hypertensive agent.

A novel taxane derivative with anticancer activity, a process for its preparation and a process for the preparation of 14-β-hydroxy-1,14-carbonate-baccatine III and V derivatives 13-substituted by an isoserine residue.

[Problems] To provide a novel taxane derivative which can release the medicinal substance in a bioenzyme-independent manner, is expected to have an effective therapeutic efficacy, and has a water-solubility.[Means for Solving Problems] Disclosed is a polymer conjugate of a taxane, which comprises a polymer having a polyethylene glycol moiety and two or more succinic acid monoamide moieties and a taxane, wherein a carboxylate group in the polymer and an alcoholic hydroxyl group in the taxane are bound to each other via an ester bonding.

The present invention is broadly directed to novel compounds useful for the synthesis of biologically active compounds, including taxane derivatives, and convergent processes for the preparation of these taxane derivatives and their intermediates.

The present invention concerns novel 7-deoxy taxane derivatives, their use as antitumor agents, and pharmaceutical formulations.

The present invention is broadly directed to novel compounds useful for the synthesis of biologically active compounds, including taxane derivatives, and convergent processes for the preparation of these taxane derivatives and their intermediates.

The application provides a process for the preparation of taxane derivatives and intermediates useful in such processes.

The present invention relates to a methods of preparing active compounds complexed with lipids using aqueous systems that are free of organic solvents, and methods of using the complexes, e.g., in treating a disease in a subject. In some embodiments, the present invention comprises a composition comprising a complex comprising at least one active compound, e.g., a polyene antibiotic, an immunosuppressant agent such as tacrolimus or a taxane or taxane derivative, and one or more lipids. In some embodiments, the present invention provides a method comprising preparing a composition comprising a lipid complex comprising at least one active compound and at least one lipid and administering the composition to a subject. In certain embodiments the subject is a mammal. In certain preferred embodiments, the subject is human.

A crystal of (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-9,10-[(1S)-2-(dimethylamino)ethylidenedioxy]-5,20-epoxy-1-hydroxytax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-3-(3-fluoro-2-pyridyl)-2-hydroxypropionate, which has characteristic peaks at diffraction angles (2θ) of 6.2°, 10.3°, 10.7°, 11.4°, and 12.0° in a powder X-ray diffraction pattern, and a method for preparing the aforementioned crystal, which comprises the step of performing crystallization by using an organic solvent selected from the group consisting of a ketone type solvent, a nitrile type solvent, and a mixture thereof, or a mixture of said organic solvent and water.

The present invention relates to compositions and methods for treating cancer, by administering a combination comprising a jasmonate derivative (e.g., methyl jasmonate or a compound of any of formulae I through VII or any of the jasmonate derivatives exemplified by such formulae) and at least one other agent selected from a chemotherapeutic agent (e.g., a nitroso-urea, a platinum compound, a taxane derivative, an antitumor antibiotic) and an inhibitor of glycolysis (e.g., 2-deoxy-D-glucose). The jasmonate derivative and the at least one other agent together provide a therapeutic effect, which is preferably synergistic (cooperative).

The present disclosure relates to processes for the preparation of taxane derivatives with improved purity and enhanced stability. The taxane derivatives prepared according to the processes described herein are useful for the preparation of pharmaceutical compositions.

Taxoid derivatives are used in the treatment of cancers, particular cancers of the central nervous system, such as brain cancers. Taxoid derivatives are transported across the blood / brain barrier (BBB). A compound is provided which consists of at least one taxoid derivative bound to at least one vector peptide capable of increasing the solubility of the derivative and advantageously allowing it to be transported across the BBB.

The application describes methods for screening subjects with breast cancer to determine if the breast cancer will be responsive to a breast cancer therapy including a taxane or a taxane derivative. The application also describes methods for treating subjects with breast cancer by screening them for the likelihood of the effectiveness of treating the cancer with a therapy including a taxane or a taxane derivative and administering the therapy in subjects when it is found that a taxane or a taxane derivative is likely to be effective.

The invention relates to (among other things) deuterated and / or fluorinated docetaxel and cabazitaxel and derivatives thereof, as well as compositions comprising each of the foregoing.

We have discovered that the administration of a G1 and / or S phase drug such as β-lapachone in combination with a G2 / M drug such as a taxane derivative such as paclitaxel resulted in a greater than additive (i.e., synergistic) reduction in the number of tumors (and tumor volume) as compared with the administration of these agents alone. In addition, no signs of toxicity or weight loss were observed. The present invention relates to a method for treating a mammalian tumor using combinations such as a taxane derivative, preferably paclitaxel, and a β-lapachone, or a derivative or analog thereof.

A crystal of (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-9,10-[(1S)-2-(dimethylamino)ethylidenedioxy]-5,20-epoxy-1-hydroxytax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-3-(3-fluoro-2-pyridyl)-2-hydroxypropionate, which has characteristic peaks at diffraction angles (2θ) of 6.2°, 10.3°, 10.7°, 11.4°, and 12.0° in a powder X-ray diffraction pattern, and a method for preparing the aforementioned crystal, which comprises the step of performing crystallization by using an organic solvent selected from the group consisting of a ketone type solvent, a nitrile type solvent, and a mixture thereof, or a mixture of said organic solvent and water.

The invention relates to a pharmaceutical combination comprising a mixture of (a) at least one taxane derivative and (b) at least one ω-3 poly-unsaturated acid or a derivative thereof wherein the molar ratio of (b) to (a) is not higher than 2. The invention further relates to a liquid pharmaceutical composition comprising (a) an effective amount of at least one taxane derivative, (b) an effective amount of at least one ω-3 poly-unsaturated fatty acid or a derivative thereof and (c) at least one pharmaceutically acceptable carrier and a process for the preparation of the same. The composition can be used for the therapy of cancers which are sensitive to taxane derivatives. The invention also relates to a kit comprising the individual components of the above mentioned composition placed in separate containers.

Pharmaceutical compositions for oral administration to mammalian subjects comprise a taxane or taxane derivative (e.g., paclitaxel or docetaxel) as active ingredient and a vehicle comprising at least 30% by weight of a carrier for the taxane, said carrier having an HLB value of at least about 10. The compositions may also comprise 0-70% of a viscosity-reducing co-solubilizer. The compositions may be incorporated into conventional oral pharmaceutical dosage forms, or can be in the form of a two-part medicament wherein the first part includes the taxane in a solubilizing vehicle and the second part comprises a carrier for the taxane to promote oral absorption. Methods of treatment of taxane-responsive disease conditions employing the novel compositions are also disclosed, whereby the compositions can be administered alone or in association with an oral bioavailability enhancing agent.