Abstract: The invention relates to water soluble antitumor analogs of paclitaxel of formula (I) wherein R1=C(O)CH2CH(OH)COOX, R2=H, C(O)CH2CH(OH)COOX, X=H, Li, Na or any other pharmaceutically acceptable counterion, as well as to a pharmaceutical composition comprising an antineoplastically effective amount of such analogs as an active ingredient.

Abstract: Taxane derivatives having alternative C2 substituents.

Abstract: Taxane derivatives having alternative C7 substituents.

Abstract: Taxane derivatives having an alkyl substituted C13 side chain.

Abstract: A method for separating paclitaxel from cephalomannin and other related compounds by obtaining a starting material that contains paclitaxel and cephalomannin; dissolving the starting material in any one of a number of particularly defined solvents such as butyl formate and butyl acetate to form a mixture; subjecting the mixture to column chromatography to obtain an eluted fraction of paclitaxel, an eluted fraction of cephalomannin and a residue; and separately drying the paclitaxel and cephalomannin fractions to obtain separate crystalline forms of paclitaxel and cephalomannin, respectively.

Abstract: New taxoids of general formula (I): their preparation and pharmaceutical compositions containing them. The new products of general formula (I) in which Z represents a radical of general formula (II): display noteworthy antitumour and antileukaemic properties.

Abstract: The present invention relates to novel benzopyranyl guanidine derivatives of the formula 1, process for preparation therof and pharmaceutical use of the benzopyranyl guanidine derivatives. The benzopyranyl guanidine derivatives of the present invention can be used for protecting heart, neuronal cell or brain damage, preserving organs, and also the benzopyranyl guanidine derivatives are pharmacologically useful for inhibiting NO generation, and for suppressing lipid peroxidation, angiogenesis or restenosis. Wherein R1, R2, R3, R4, R5, R6, n and * are each defined in specification.

Abstract: Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.

Abstract: Process for synthesizing paclitaxel by treating baccatin III with a strong base in a solvent, adding an electrophile to the solution to form a 7-O-protected baccatin III derivative, reacting the 7-O-protected baccatin III derivative with a protected paclitaxel sidechain in a solvent such that the protected paclitaxel sidechain is coupled to the 13-hydroxyl of the 7-O-protected baccatin III, and subsequently deprotecting the protected paclitaxel sidechain and the 7-O protecting group to form paclitaxel, and intermediates used therein.

Abstract: The present invention concerns antitumor compounds. More particularly, the invention provides novel taxane derivatives, pharmaceutical compositions thereof, and their use as antitumor agents.

Abstract: This invention provides a taxane derivative of the formula: wherein a hydrophobic organic moiety is attached to a taxane. R and R1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R1 is not H. Attachment of a hydrophobic organic moiety to the taxane so as to obtain a taxane derivative generally stabilizes the association of the derivative with a lipid, including a liposomal lipid, carrier in the plasma of animals to which the derivative-carrier association is administered. Also provided herein is a composition containing the taxane derivative and a pharmaceutically acceptable medium; desirably, the medium also contains a lipid carrier, and the derivative is associated with the carrier. Further provided herein is a method of administering taxane derivatives to animals, for example, animals afflicted with cancers.

Abstract: Process for the preparation of a derivative or analog of baccatin III or 10-desacetyl baccatin III having a C9 substituent other than keto in which the C9 keto substituent of taxol, a taxol analog, baccatin III or 10-desacetyl baccatin III is selectively reduced to the corresponding hydroxy group.

Abstract: Processes for the preparation of taxol and other taxanes through selective derivatization of the C(7) and C(10) hydroxyl groups of 10-DAB, particularly a novel process using a new strategy in which the C(10) hydroxyl group is protected or derivatized prior to the C(7) hydroxyl group; and the provision of C(7) and C(10) derivatized 10-DAB compounds.

Abstract: Polymerizable and hydrolysable oxetane silanes and in particular silicic acid condensates which can be prepared therefrom are described, which exhibit only a low volume shrinkage on polymerization and produce polymers with high mechanical strength and therefore can be used above all as dental material or constituent thereof.

Abstract: A process for producing 10-deacetyl baccatin III from an acidic solution containing a spectrum of taxanes, comprising contacting the acidic solution containing the spectrum of taxanes with a hydrazine hydrate, thereby to convert into 10-deacetyl baccatin III some taxanes in said solution that are not 10-deacetyl baccatin III.

Abstract: Onium salts of taxo-diterpenoid-Cn,2-O-aza-arenes form water soluble self-assembling nanostructures above a critical aggregation concentration. The onium salt of aza-arene includes a delocalized charge which renders derivatized taxo-diterpenoids amphoteric, enhances their solubility in water, and promotes self-assembly of water soluble nanostructures, e.g., helical fibular structures and spherical micellular structures. These same onium salts of taxo-diterpenoid-Cn,2-O-aza-arenes are employed as water soluble prodrugs. For example, taxol-2′-methylpyridinium tosylate (MPT) is characterized by an elevated aqueous solubility, rapid activation by serum protein, good stability in most other aqueous solutions, formation of a protein:taxol intermediate and good retention within the circulatory system. The toxicity of the activated form is comparable or greater than underivatized taxol. Furthermore, taxol-2′-MPT can be synthesized by a simple one step reaction between taxol and 2-fluoro-1-MPT.

Abstract: Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble chelator, polyethylene glycol or polymer such as poly (1-glutamic acid) or poly (1-aspartic acid). Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis and for prediction of paclitaxel uptake by tumors and radiolabeled DTPA-paclitaxel tumor imaging. Other embodiments include the coating of implantable stents for prevention of restenosis.

Abstract: The present invention relates to chemical compounds that are useful in the production of taxanes. The chemical compounds according to the present invention have a generalized formula: wherein R1 is NH2, and wherein R2 may be acetyl or hydrogen, and p1 may be hydrogen or a hydroxyl protecting group.

Abstract: Cyclic chemical switching method is employed for solubilizing and desolubilizing taxo-diterpenoids with respect to aqueous solvents. 2-Halogenated onium salts of aza-arenes are employed to derivatize taxo-diterpenoids so as to alter their solubility in aqueous solvents. The onium salt of aza-arene includes a delocalized charge which imparts polarity and aqueous solubility to taxo-diterpenoid derivatives. Solubilization is achieved in a one step derivatization with the onium salt of 2-halogenated aza-arenes. Desolubilization is achieved by contacting onium salts of taxo-diterpenoid-Cn,2-O-aza-arenes with serum protein to displace the 2-O-aza-arene and form a soluble protein:taxo-diterpenoid intermediate. This protein:taxo-diterpenoid intermediate then dissociates over time to provide a bioactive taxo-diterpenoid. These same onium salts of taxo-diterpenoid-Cn,2-O-aza-arenes are employed as water soluble prodrugs. The toxicity of the activated form is comparable or greater than underivatized taxol.

Abstract: Methods of preparing new taxoids of general formula (I) are presented: in which: R4 represents an alkanoyloxy radical in which the alkanoyl portion contains 2 to 6 carbon atoms in an unbranched or branched chain, this radical unsubstituted or substituted with one or more halogen atoms, an alkoxy radical containing 1 to 4 carbon atoms, or alternatively R4 represents a cycloalkanoyloxy radical in which the cycloalkanoyl portion contains 4 to 8 carbon atoms, or alternatively R4 represents a benzoyloxy radical; R5 represents an alkoxy radical containing 1 to 4 carbon atoms, substituted by an alkylthio radical containing 1 to 4 carbon atoms; and Z represents a hydrogen atom or a radical of general formula:

Abstract: The object of the present invention is the development of new chiral auxiliaries for improved &bgr;-lactam formation that control both the diastereoselectivity of &bgr;-lactam formation and which can be removed without destruction of the sensitive azetidinone ring, providing valuable intermediates for coupling to the C-13 hydroxyl group of anti-tumor taxanes, such as paclitaxel. Further, the object of the present invention is enantiomerically pure (S)-(−)-1-(p-methoxy-phenyl)propyl-1-amine.

Abstract: The present invention relates to a semi-synthetic process to convert a naturally occurring taxane into a suitable starting material for the synthesis of paclitaxel and related compounds. Specifically, the present invention relates to a process for the conversion of 9-dihydro-13-acetylbaccatin III into a 7-protected baccatin III which can then be used as starting material for the synthesis of taxane derivatives such as paclitaxel, docetaxel, cephalomannine and other taxanes structurally related to baccatin III. The method as described uses a preparative scale technique which is amenable to commercial scale-up.

Abstract: Taxol (I) is a complex deterpene which is currently considered the most exciting lead in cancer chemotherapy. Taxol possesses high cytotoxicity and strong antitumor activity against different cancers which have not been effectively treated by existing antitumor drugs. However, taxol has a problem with solubility in aqueous media, which may impose some serious limitation in its use. Taxotére (III) seems to have antitumor activity superior to taxol with better bioavailability. Taxotére has a modified taxol structure with a modified C-13 side chain. This fact strongly indicates that modification on the C-13 side chain would provide a new series of taxol and Taxotére analogues which may have higher potency, better bioavailability and less unwanted toxicity. The present invention provides efficient and practical methods for the syntheses of Taxotére and its analogues through &bgr;-lactam intermediates and their coupling with baccatin III.

Abstract: The present invention concerns novel 7-ethers of taxane derivatives, their use as antitumor agents and pharmaceutical compositions containing the novel compounds.

Abstract: 4-acetoxy-2&agr;-benzoyloxy-5&bgr;, 20-epoxy-1&bgr;, 7&bgr;, 10&bgr;-trihydroxy-9-oxo-11-taxen-13&agr;-y1(2R,3S)-3-t-butoxycarbonylamino-3-phenyl-2-hydroxypropionate trihydrate obtained by a process of centrifugal partition chromatography.

Abstract: Process for preparing taxol, baccatin III and 10-deacetylbaccatin III by oxidation of 9-dihydro-13-acetylbaccatin III.

Abstract: The present invention describes for the first time the design and synthesis of a soluble tumor-directed paclitaxel prodrug which may establish a new mode of utilization of the taxane class of anticancer agents in cancer therapy.

Abstract: Processes for the preparation of taxol and other taxanes through selective derivatization of the C(7) and C(10) hydroxyl groups of 10-DAB, particularly a novel process using a new strategy in which the C(10) hydroxyl group is protected or derivatized prior to the C(7) hydroxyl group; and the provision of C(7) and C(10) derivatized 10-DAB compounds.

Abstract: A process for the preparation of a taxane derivative of the formula in which R2 represents an RO—, RS— or RR′N— in which R represents an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl, or cycloalkyl, saturated heterocyclic, cycloalkenyl, unsaturated heterocyclic, aryl or heterocyclic aromatic; R′ is a hydrogen or R defined above; R and R′ can be connected to form together with the nitrogen a cyclic structure; Y is oxygen or sulfur; R3 represents an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, cycloalkenyl or an unsubstituted or substituted aryl; which comprises reacting a &bgr;-lactam of the formula in which R311 represents a radical R3 defined above or a protected R3 whenever R3 includes one or more active hydrogens; with a baccatin III derivative of the formula: in which M is an alkali metal

Abstract: Novel reaction conditions for the cleavage of silyl ethers from silyl protected taxane precursors to afford paclitaxel and paclitaxel analogues in high yield and quality are described. Paclitaxel is prepared from a taxane precursor by treating the taxane precursor with a strong acid such as trifluoroacetic acid in a solvent such as aqueous acetic acid, such that the amount and number of side reactions and taxane impurities are significantly minimized. Also desribed are the crystallization methods for the isolation of paclitaxel in either of the two crystal forms A or B. Paclitaxel and paclitaxel analogues are anti-cancer agents.

Abstract: New processes for the selective protection of the 7-position of 7,10-dihydroxytaxane derivatives, using &bgr;-substituted-alkoxycarbonyl groups which are more hindered than 2,2,2-trichloroethoxycarbonyl, and which are capable of being removed by a &bgr;-elimination mechanism, and the new intermediates resulting from these processes. The new intermediates of the invention are useful for preparing taxol and analogs thereof.

Abstract: The present invention provides a 3″-monohalocephalomannine of the formula: wherein R is halogen.

Abstract: Nucelophilic group, such as alcohol, terminated 2-oxetanone multimers, process of making same by reacting e.g. alcohol and dicarboxylic acid chloride in the presence of triethylamine, and their use for sizing paper.

Abstract: Compounds of the formula of are disclosed as well as a method of preparation.

Abstract: Novel taxoids of general formula (I), the preparation thereof and pharmaceutical compositions containing same, are disclosed. In general formula (I), Z is a hydrogen atom or a radical of general formula (H), wherein R.sub.1 is an optionally substituted benzoyl radical or a radical R.sub.2 --O--CO--, where R.sub.2 is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, optionally substituted phenyl or heterocyclyl radical; R.sub.3 is an alkyl, alkenyl, alkyl, cycloalkyl, phenyl, naphthyl or aromatic heterocyclic radical; R.sub.4 is a hydroxy radical or an alkoxy, alkenyloxy, optionally substituted alkynyloxy, alkanoyloxy, alkenoyloxy, alkynyloxy, alkoxyacetyl or alkyloxycarbonyloxy radical, or a cycloalkyloxy, cycloalkenyloxy, arylcarbonyloxy or heterocyclylcarbonyloxy radical; and R.sub.5 is an optionally substituted alkoxy radical or a cycloalkyloxy or cycloalkenyloxy radical.

Abstract: Novel 2'-onium salts of paclitaxel act as prodrugs in mammalian patients to yield paclitaxel in vivo. Methods of synthesizing these onium salts are disclosed, as are methods of treating patients suffering from paclitaxel-responsive diseases by administering effective amounts of the onium salts and pharmaceutical compositions containing the novel salts which are suitable for administration to patients requiring paclitaxel therapy.

Abstract: A pharmaceutical composition comprising an effective cancerous cell growth inhibiting amount of paclitaxel, or a paclitaxel derivative, and an effective cancerous cell growth inhibiting amount of an active agent which inhibits cancerous cell growth by exerting an effect on mammalian cell cycle during G.sub.1 or S-phase of the cell division cycle to inhibit said cancerous cell growth and methods of using same.

Abstract: The present invention is directed to 4,10.beta.-diacetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1-hydroxy-9-oxo- 19-norcyclopropa(g)tax-11-en-13.alpha.-yl (2r,3s)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate dihydrate and a process for its preparation.

Abstract: Taxane derivatives having alternative C9 substituents.

Abstract: 1-Alkyl-4-benzoyl-5-hydroxy-1H-pyrazole compounds in which the benzoyl moiety is substituted in the 2-position with groups such as halo or alkyl, in the 4-position with an alkylsulfonyl group, and in the 3-position with a 3-oxetanyloxy or an oxetanylmethoxy substituent were prepared and found to be useful for the control of a variety of broadleaf and grassy weeds. The compounds have favorable environmental and toxicological properties and can be used to control undesirable vegetation in crops.

Abstract: 2-Benzoylcyclohexane-1,3-diones of the formula I: ##STR1## where: R.sup.1 and R.sup.2 are each hydrogen, mercapto, nitro, halogen, cyano, thiocyanato, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -haloalkyl, C.sub.1 -C.sub.6 -alkoxy, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, --OR.sup.10, --OCOR.sup.10, --OSO.sub.2 R.sup.10, --S(O).sub.n R.sup.10, --SO.sub.2 OR.sup.10, --SO.sub.2 NR.sup.3 R.sup.10, --NR.sup.10 SO.sub.2 R.sup.10 or --NR.sup.10 COR;Q is a cyclohexane-1,3-dione ring with or without substitution, which is attached in position 2;A is a group of the formula IIa, IIb or III: ##STR2## where the substituents are as defined in claim 1, and agriculturally useful salts thereof are described.

Abstract: Highly specific biocatalytic reactions have been used to create a population of derivatives from a single starting compound. Examples demonstrate synthesis of derivatives of taxol, taxol-2'-adipate, taxol-2'-vinyl adipate, 2,3-(methylenedioxy) benzaldehyde, (.+-.)-(2-endo, 3-exo)-bicyclo (2.2.2)octo-5-ene-2,3-dimethanol, adenosine and erythromycin.

Abstract: A method of isolating paclitaxel from pactitaxel-containing material that includes the steps of obtaining an acetone mixture of the paclitaxel-containing material, then mixing the acetone mixture with an aqueous solvent to form an aqueous supernatant and a precipitate, wherein the precipitate contains at least 3-times higher paclitaxel content than the paclitaxel extract. The acetone/water precipitation step provides a high yield of highly pure paclitaxel that is suitable for industrial scale isolation using conventional normal-phase silica chromatography steps, and the preparation of pharmaceutical compositions containing paclitaxel.

Abstract: An antitumor compound of formula (5) ##STR1## and also provided by the present invention is a method of preparing a compound of formula (5) whereby diesterification of the alcohol groups located at the 2' and 7 positions of paclitaxel is followed by the hydrolysis of the 2' hexanoate group resulting in 7-hexanoyltaxol.

Abstract: A chemical compound having the formula: ##STR1## wherein P.sub.1 is a hydroxyl protecting group, R.sub.1 may be H or electron withdrawing group, R.sub.2 may be H or electron withdrawing group, R.sub.3 may be H or electron withdrawing group, R.sub.4 may be H or electron withdrawing group, R.sub.5 may be H or electron withdrawing group, R.sub.6 may be an alkyl group, an olefinic group, an aromatic group, Ph, PhCH.sub.2, an O-alkyl group, an O-olefinic group, an O-aromatic group, O--Ph, or O--CH.sub.2 Ph.

Abstract: A compound for use in the production of taxanes and intermediates therefor having the formula: ##STR1## wherein R is an alkyl group.

Abstract: A process for selective monoacylation of 10-deacetylbaccatin III, or a derivative thereof in positions C-2 and C-4 possessing free hydroxyl groups in positions C-7 and C-10, using a methyleneiminium salt.

Abstract: A process for preparing N-acyl, N-sulfonyl and N-phosphoryl substituted isoserine esters in which a metal or an ammonium alkoxide is reacted with a .beta.-lactam.

Abstract: This invention provides a taxane derivative of the formula: ##STR1## wherein a hydrophobic organic moiety is attached to a taxane. R and R.sup.1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R.sup.1 is not H. Attachment of a hydrophobic organic moiety to the taxane so as to obtain a taxane derivative generally stabilizes the association of the derivative with a lipid, including a liposomal lipid, carrier in the plasma of animals to which the derivative-carrier association is administered. Also provided herein is a composition containing the taxane derivative and a pharmaceutically acceptable medium; desirably, the medium also contains a lipid carrier, and the derivative is associated with the carrier. Further provided herein is a method of administering taxane derivatives to animals, for example, animals afflicted with cancers.

Abstract: A .beta.-phenylisoserine derivative of general formula (I): ##STR1## in the form of a salt or an ester, in which Ar represent an aryl radical, R represents a phenyl or naphthyl or a O--R.sub.1 radical and G.sub.1 represents --CH.sub.2 --Ph radical; and a method of using the same for making taxane derivatives.