The Hetero Ring Is Four-membered Patents (Class 549/510)
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Patent number: 6130336Abstract: The present invention elates to a process for preparing paclitaxel represented by formula (1) characterized in that: (a) an oxazolidine derivative represented by formula (2) or its salt in which X represents halogen, is coupled with a 7-trihaloacetyl-baccatin III represented by formula (3) in which R.sub.1 represents trihaloacetyl, in a solvent in the presence of a condensing agent to produce an oxazolidine substituent-containing taxane represented by formula (4) in which X and R.sub.1 are each as previously defined; (b) the oxazolidine ring is opened in a solvent in the presence of an acid, and the product thus obtained is reacted with benzoyl chloride in the presence of a base to produce a protected paclitaxel wherein the hydroxy group at 7-position is protected with trihaloacetyl group represented by formula (5) in which R.sub.1 is as previously defined; (c) then the protecting group at 7-position is removed by ammonia or a salt of ammonia with a weak acid in a solvent.Type: GrantFiled: February 23, 1999Date of Patent: October 10, 2000Assignee: Hanmi Pharm., Co. Ltd.Inventors: Kyoung Soo Kim, Ki Byung Chai, Young Ho Moon, Kwang Ok Lee, Nam Du Kim, Tae Hee Ha, Jung Ae Shin, Gwan Sun Lee, Wan Joo Kim
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Patent number: 6127555Abstract: 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.Type: GrantFiled: May 5, 1999Date of Patent: October 3, 2000Assignee: Aventis Pharma S.A.Inventors: Eric Didier, Pascal Pecquet
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Patent number: 6124481Abstract: 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.Type: GrantFiled: September 26, 1997Date of Patent: September 26, 2000Assignee: Florida State UniversityInventor: Robert A. Holton
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Patent number: 6124482Abstract: A novel process for isolation of 10-deacetyl baccatin-III (10-DAB) and also complete separation of paclitaxel present in the primary extract, on a commercial scale from plant extract of Taxus species by solvent crystallization without employing chromatographic separation.Type: GrantFiled: September 7, 1999Date of Patent: September 26, 2000Assignee: Dabur Research FoundationInventors: Sunder Ramadoss, Anand Vardhan
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Patent number: 6118011Abstract: 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.Type: GrantFiled: November 27, 1996Date of Patent: September 12, 2000Assignee: The Liposome Company, Inc.Inventors: Eric Mayhew, J. Craig Franklin, Suresh Bhatia, Paul A. Harmon, Andrew S. Janoff
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Patent number: 6114550Abstract: 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.Type: GrantFiled: November 10, 1997Date of Patent: September 5, 2000Assignee: Rhone-Poulenc Rorer S.A.Inventors: Jean-Noel Denis, Andrew-Elliot Greene, Alice Kanazawa
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Patent number: 6114551Abstract: A method of synthesizing an olefin epoxidation catalyst comprises the step of treating a porous crystalline aluminosilicate material having an X-ray diffraction pattern including d-spacing maxima at 12.4.+-.0.25, 6.9.+-.0.15, 3.57.+-.0.07 and 3.42.+-.0.07 Angstrom, such as MCM-22, with a dealuminating agent under conditions effective to remove framework aluminium from the material and produce a dealuminated product. The dealuminated product is then treated with a titanium-containing material under conditions effective to insert titanium into the dealuminated product and produce a titanium-containing, dealuminated catalyst composition.The resultant catalyst is useful in the epoxidation of olefins, such as propylene and cyclohexene, with hydrogen peroxide and organic hydroperoxides.Type: GrantFiled: October 4, 1999Date of Patent: September 5, 2000Assignee: Mobil Oil CorporationInventors: Doron Levin, Clarence D. Chang, Shifang Luo, Jose G. Santiesteban, James C. Vartuli
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Patent number: 6113816Abstract: A kit for detecting a first substance in a sample comprising a dioxetane having the formula: ##STR1## wherein T is a cycloalkyl or polycycloalkyl group bonded to the 4-membered ring portion of the dioxetane by a spiro linkage; Y is a fluorescent chromophore; X is H, alkyl, aryl, aralkyl, alkaryl, heteroalkyl, heteroaryl, cycloalkyl, cycloheteroalkyl, or an enzyme-cleavable group; and Z is H or an enzyme-cleavable group, provided that at least one of X or Z must be an enzyme-cleavable group; and an enzyme which cleaves the enzyme-cleavable group of the dioxetane creating an electron-rich moiety which destabilizes the dioxetane, causing it to decompose into two ketones, one ketone comprising the moiety T, and the other ketone comprising moieties X, Y and a portion of Z. The energy released by decomposition causes the moiety Y to luminesce.Type: GrantFiled: October 30, 1998Date of Patent: September 5, 2000Assignee: Tropix, Inc.Inventor: Irena Y. Bronstein
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Patent number: 6107333Abstract: Disclosed is a stable and effective formulation of a taxane analog, preferably paclitaxel. The formulation comprises a dimethylacetamide and polyethylene glycol solution of the drug that is diluted into an aqueous lipid emulsion prior to use. The formulation is effective as a parenterel drug against taxane sensitive tumors.Type: GrantFiled: March 1, 1999Date of Patent: August 22, 2000Inventor: Borje S. Andersson
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Patent number: 6107497Abstract: C7, C10 di-CBZ 10-deacetyl baccatin III of the formula: ##STR1## provides an intermediate for the production of docetaxel. A method of producing this C7, C10 di-CBZ 10-deacetyl Baccatin III is provided. Here, 10-deacetyl Baccatin III is acylated with at least 1.5 equivalents of n-butyl lithium and at least 1.5 equivalents of benzyl chloroformate in tetrahydrofuran. The 10-deacetyl Baccatin III may first be dissolved in tetrahydrofuran after which the n-butyl lithium is added followed by the addition of the benzyl chloroformate. The reaction is preferably at a reduced temperature of less than -20.degree. C. The resulting solution may be quenched with ammonium chloride and reduced to residue. The residue may then be redissolved in an organic solvent, washed, dried and recrystallized to purify the compound.Type: GrantFiled: March 19, 1996Date of Patent: August 22, 2000Assignees: NaPro BioTherapeutics, Inc., Bryn Mawr CollegeInventors: Nicholas J. Sisti, Charles S. Swindell, Madhavi C. Chander
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Patent number: 6100411Abstract: This invention relates to a taxoid of the formula (I): ##STR1## wherein R.sup.1 is a C.sub.3 -C.sub.5 alkyl or alkenyl or trifluoromethyl radical;R.sup.2 is a C.sub.3 -C.sub.5 branched alkyl radical;R.sup.3 and R.sup.4 are independently selected from hydrogen and hydroxyl protecting groups including functional groups which increase the water solubility of the taxoid antitumor agent;R.sup.5 is a hydrogen, an acyl radical, or an alkoxylcarbonyl or carbamoyl radical; andR.sup.6 is an acyl radical.The compounds of formula I are useful as antitumor agents or their precursors. This invention also relates to a pharmaceutical composition having antineoplastic activity comprising the compound of formula (I) and a physiologically acceptable carrier and method of treatment using the compound of formula I.Type: GrantFiled: March 4, 1996Date of Patent: August 8, 2000Assignee: The Research Foundation of State University of New YorkInventor: Iwao Ojima
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Patent number: 6096909Abstract: This invention relates to a taxoid of the formula (I) ##STR1## wherein R.sup.1 is 1-propenyl radical;R.sup.2 is a C.sub.3 -C.sub.5 branched alkyl radical;R.sup.3 and R.sup.4 are independently selected from hydrogen and hydroxyl protecting groups including functional groups which increase the water solubility of the taxoid antitumor agent;R.sup.5 represents a hydrogen or a hydroxyl protecting group;R.sup.6 represents an acyl radical,which are useful as antitumor agents or their precursors. A pharmaceutical composition having antineoplastic activity comprising the compound of formula (I) and a physiologically acceptable carrier and method of treatment are also disclosed.Type: GrantFiled: August 13, 1997Date of Patent: August 1, 2000Assignee: The Research Foundation of State University of New YorkInventor: Iwao Ojima
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Patent number: 6096903Abstract: 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.Type: GrantFiled: March 25, 1998Date of Patent: August 1, 2000Assignee: Ivoclar AGInventors: Norbert Moszner, Thomas Voelkel, Sabine Stein, Volker Rheinberger
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Patent number: 6090951Abstract: Novel methods for the preparation of sidechain-bearing taxanes, comprising the preparation of an oxazoline compound, coupling the oxazoline compound with a taxane having a hydroxyl group directly bonded at C-13 thereof to form an oxazoline sidechain-bearing taxane, and opening the oxazoline ring of the oxazoline sidechain-bearing taxane so formed. Novel compounds prepared by the methods of the present invention are also provided.Type: GrantFiled: August 25, 1997Date of Patent: July 18, 2000Inventors: Michael A. Poss, Jerome L. Moniot, Ivan D. Trifunovich, David J. Kucera, John K. Thottahil, Shu-Hui Chen, Jianmei Wei
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Patent number: 6090955Abstract: The aim of the invention is to produce liposome-encapsulated taxol with a high taxol concentration and high stability and hence a high therapeutic effect. The invention involves the development of specific forms of taxol encapsulation and the use of these, optionally in combination with other substances, in the treatment of various types of tumor. The liposome-encapsulated taxol is characterized in that it is prepared by high-pressure homogenization or by aerosol formulation.Type: GrantFiled: June 19, 1997Date of Patent: July 18, 2000Assignee: Max-Delbruck-Centrum fur Molekulare MedizinInventors: Regine Reszka, Martin Brandl, Iduna Fichtner, Gernot Warnke
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Patent number: 6080733Abstract: The invention relates to thioureido-cyclodextrins, usable in particular to solubilize anti-tumor and antiparasitic agents and their preparation processes.These thioureido-cyclodextrins correspond to the formula: ##STR1## with m=6, 7 or 8, R.sup.1 represents OH or NH--CS--NHR.sup.2, at least one of the R.sup.1 being NH--CS--NHR.sup.2,R.sup.2 represents an alkyl, monosaccharide, oligosaccharide glycosyl-amino acid or glycopeptide group.These cyclodextrins are usable for solubilizing anti-tumor or antiparasitic agents of the Taxol family.Type: GrantFiled: October 20, 1998Date of Patent: June 27, 2000Assignee: Centre National de la Recherche ScientifiqueInventors: Jacques Defaye, Carmen Ortiz-Mellet, Jose-Manuel Garcia-Fernandez
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Patent number: 6080877Abstract: The invention provides taxanes that are conjugates of cis-docosahexaenoic acid and taxotere. The conjugates are useful in treating cancer.Type: GrantFiled: June 3, 1997Date of Patent: June 27, 2000Assignee: Neuromedica, Inc.Inventors: Charles S. Swindell, Victor E. Shashoua, Matthews O. Bradley, Nigel L. Webb
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Patent number: 6072060Abstract: An efficient protocol for the synthesis of taxol, taxol analogs and their intermediates is described. The process incudes the attachment of the taxol A-ring side chain to baccatin III and for the synthesis of taxol and taxol analogs with variable A-ring side chain structures. A rapid and highly efficient esterification of O-protected isoserine and 3-phenylisoserine acids having N-benzyoloxycarbonyl groups to the C-13 hydroxyl of 7-O-protected baccatin III is followed by a deprotection-acylation sequence to make taxol, cephalomanninne and various analogs, including photoaffinity labeling candidates.Type: GrantFiled: February 19, 1999Date of Patent: June 6, 2000Assignee: Bryn Mawr CollegeInventors: Charles S. Swindell, Nancy Krauss
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Patent number: 6069260Abstract: A process for preparing N-acyl, N-sulfonyl and N-phosphoryl substituted isoserine esters in which a metal alkoxide is reacted with a .beta.-lactam.Type: GrantFiled: September 30, 1997Date of Patent: May 30, 2000Assignee: Florida State UniversityInventor: Robert A. Holton
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Patent number: 6066749Abstract: A method of acylating C-2' O-protected-10-hydroxy taxol selectively at the C-10 hydroxyl position over the C-7 hydroxy position thereof to produce C-2' O-protected taxol is accomplished first by dissolving C-2' O-protected-10-hydroxy taxol in an acceptable ether solvent therefor, such as tetrahydrofuran, to form a first solution at a first temperature. The first solution is then cooled to a second temperature, and a lithium base, preferably n-butyl lithium, is added to form an intermediate compound having a lithium alkoxide at the C-10 position thereof. An acylating agent, such as acetyl chloride, is then added. The resulting solution may be quenched, for example with ammonium chloride, to eliminate excess of the acylating agent and the lithium base. The result is a solution containing C-2' O-protected taxol. This solution may then be washed, concentrated and purified. The present invention is also directed to C-10 lithium alkoxide intermediate compounds for the production of paclitaxel.Type: GrantFiled: May 1, 1998Date of Patent: May 23, 2000Assignee: NaPro BioTherapeutics, Inc.Inventors: Nicholas J. Sisti, Herbert R. Brinkman, James D. McChesney, Madhavi C. Chander, Xian Liang, Jan Zygmunt
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Patent number: 6066748Abstract: The present invention teaches a method of extracting TAXOL.RTM. from the leaves of taxus cupidata plants. The process comprises a series of steps, including the concentration of the extracts obtained from the plant, the separation of the aqueous and chloroform phases, and several purification procedures. In addition, the present invention teaches a multi-step process wherein the virtual removal of chlorophyll is achieved prior to the introduction of the extract into the silica gel packing material. This prevents the deactivation of the silica gel packing material by chlorophyll in the extract solution.Type: GrantFiled: May 8, 1998Date of Patent: May 23, 2000Inventors: Man Woo Han, Jae Kuk Yoo, Nam Doo Hong
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Patent number: 6066747Abstract: A derivative or analog of baccatin III or 10-desacetyl baccatin III having a C-9 substituent other than keto.Type: GrantFiled: October 30, 1995Date of Patent: May 23, 2000Assignee: Florida State UniversityInventors: Robert A. Holton, Carmon Somoza, Yukio Suzuki, Mitsuru Shindo
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Patent number: 6063939Abstract: Unsaturated cyclic ethers of the formula I ##STR1## whereZ is --(CHR.sup.4).sub.q -- or --(CHR.sup.4).sub.q --O--,q is 0, 1, 2 or 3 andR.sup.1,R.sup.2,R.sup.3,R.sup.4 are hydrogen or C.sub.1 -C.sub.4 -alkylare prepared by reacting diols of the formula II ##STR2## where Z, R.sup.1, R.sup.2 and R.sup.3 are as defined above, in the liquid phase at from 150 to 300.degree. C. in the presence of a cobalt-containing supported catalyst which has not been activated by reduction before use and comprises cobalt and a noble metal selected from the group consisting of platinum, palladium, rhodium, iridium, ruthenium, osmium, rhenium or a mixture thereof applied by sol impregnation on an inert support, wherein the supported catalyst is doped with sulfur. Sulfur-doped supported catalysts comprising cobalt and noble metals are also provided.Type: GrantFiled: January 7, 1999Date of Patent: May 16, 2000Inventors: Carsten Groning, Michael Hesse, Daniel Heineke, Heinz-Josef Kneuper, Gerhard Fritz
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Patent number: 6057359Abstract: Spontaneously dispersible concentrates comprising new esters of Baccatin-III, 10-Deacetylbaccatin-III and 14-OH-10-Deacetylbaccatin-III, procedures for their production. The preparation of aqueous ultramicroemulsions, their incorporation into pharmaceutical compositions having antitumor, antiviral and virucidal activity, are efficacious in the treatment of eczemae and psoriasis and stimulate the increased absorption of exogenous activators, regulators or modulators, are described.Type: GrantFiled: June 11, 1997Date of Patent: May 2, 2000Assignee: Marigen S.A.Inventor: Carl Eugster
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Patent number: 6051600Abstract: Provided herein is a taxane having a hydrocarbon attached at the 2' and/or 7 positions, the hydrocarbon's alpha position being occupied by a "hydrolysis-promoting group" ("HPG"). Substitution of an HPG for the methylene unit ordinarily occupying the alpha position allows for enhanced in vivo hydrolysis of the hydrocarbon-taxane bond, and hence, for enhanced taxane therapeutic activity. Also provided herein are taxane-containing compositions, and methods of administering taxanes to animals, including those afflicted with cancers.Type: GrantFiled: February 27, 1997Date of Patent: April 18, 2000Inventors: Eric Mayhew, Shaukat Ali, Andrew S. Janoff
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Patent number: 6051724Abstract: Taxane derivatives having an amino substituted C13 side chain.Type: GrantFiled: October 20, 1997Date of Patent: April 18, 2000Assignee: Florida State UniversitiyInventors: Robert A. Holton, Hossain Nadizadeh, Kasthuri Rengan, Chunlin Tao
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Patent number: 6048990Abstract: A method of acylating C-2' O-protected-10-hydroxy taxol selectively at the C-10 hydroxyl position over the C-7 hydroxy position thereof to produce C-2' O-protected taxol is accomplished first by dissolving C-2' O-protected-10-hydroxy taxol in an acceptable ether solvent therefor, such as tetrahydrofuran. A lithium salt, preferably lithium chloride, is added. A trialkylamine base or pyridine is next added, followed by the addition of an acylating agent, such as acetyl chloride. The resulting solution may be quenched, for example with ammonium chloride, to eliminate excess of the acylating agent. This solution may then be diluted with ethyl acetate to form an organic phase and an aqueous phase, with the organic phase being washed and thereafter reduced. Recrystallization and column chromatography may be employed to purify the C-2' O-protected taxol.Type: GrantFiled: May 1, 1998Date of Patent: April 11, 2000Assignee: NaPro BioTherapeutics, Inc.Inventors: Xian Liang, Jan Zygmunt, Nicholas J. Sisti, Madhavi C. Chander, Herbert R. Brinkman, James D. McChesney
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Patent number: 6043382Abstract: A method for esterifying C13 deoxy taxoid intermediates employs three steps, i.e., oxygenation of the C13 deoxy taxoid intermediate to produce a C13 enone taxoid intermediate; reduction of the C13 enone to produce an alcohol; followed by esterification of the C13 alcohol. Key intermediates include C13 deoxy taxoids; C13 enone substituted taxoids; and C1-C2 cyclo carbonate esters of taxoids.Type: GrantFiled: July 28, 1998Date of Patent: March 28, 2000Assignee: The Scripps Research InstituteInventors: K.C. Nicolaou, Philippe G. Nantermet, Rodney K. Guy, Hiroaki Ueno
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Patent number: 6040465Abstract: Disclosed is a process for producing an optically active .beta.-lactone represented by the general formula (I): ##STR1## wherein R.sup.1 represents an alkyl group having 1-9 carbon atoms which can be branched or a cycloalkyl group having 5-7 carbon atoms. The process comprises reacting an aldehyde represented by the general formula (II):R.sup.1 CHO (II)wherein R.sup.1 is the same as defined above, with a ketene represented by the general formula (III):CH.sub.2 .dbd.C.dbd.O (III)in the presence of a bissulfonamide/aluminum complex represented by the general formula (IV): ##STR2## wherein Ar represents 2,4,6-(R.sup.2).sub.3 C.sub.6 H.sub.2 (wherein R.sup.2 represents an alkyl group having 2-4 carbon atoms), Et represents an ethyl group and Ph represents a phenyl group.Type: GrantFiled: March 10, 1999Date of Patent: March 21, 2000Assignee: Takasago International CorporationInventors: Sotaro Miyano, Tetsutaro Hattori, Osamu Uesugi, Yasufumi Tamai, Noboru Sayo
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Patent number: 6040466Abstract: New taxoids and methods of preparing new taxoids of general formula (I): ##STR1## in which: R.sub.4 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 R.sub.4 represents a cycloalkanoyloxy radical in which the cycloalkanoyl portion contains 4 to 8 carbon atoms, or alternatively R.sub.4 represents a benzoyloxy radical;R.sub.5 represents an alkoxy radical containing 1 to 4 carbon atoms, substituted by an alkylthio radical containing 1 to 4 carbon atoms; andZ represents a hydrogen atom or a radical of general formula: ##STR2## wherein such new taxoids display noteworthy anti-tumor and anti-leukemic properties.Type: GrantFiled: March 17, 1999Date of Patent: March 21, 2000Assignee: Rhone Poulenc Rorer SAInventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commer.cedilla.on
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Patent number: 6036892Abstract: Stable, enzymatically triggered chemiluminescent 1,2-dioxetanes with improved water solubility and storage stability are provided as well as synthetic processes and intermediates used in their preparation. Dioxetanes further substituted with two or more water-solubilizing groups disposed on the dioxetane structure and an additional fluorine atom or lower alkyl group provide superior performance by eliminating the problem of reagent carryover when used in assays performed on capsule chemistry analytical systems. These dioxetanes display substantially improved stability on storage. Compositions comprising these dioxetanes, a non-polymeric cationic surfactant enhancer and optionally a fluorescer, for providing enhanced chemiluminescence are also provided.Type: GrantFiled: July 7, 1998Date of Patent: March 14, 2000Assignee: Lumigen, Inc.Inventors: Zahra Arghavani, Hashem Akhavan-Tafti, Renuka DeSilva, Kumar Thakur
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Patent number: 6030818Abstract: The present invention relates to a method of obtaining different biologically pure cultures of bacteria isolated from different species of Taxus such as Taxus canadensis. T. brevifolia, T. baccata, T. cuspidata, and T. hunnewelliana, wherein the bacteria produce in vitro taxanes and paclitaxel, and wherein the bacteria are of the genus Sphingomonas, Bacillus, Pantoea or Curtobacterium. Also, the present invention relates to a method of a bacterial mass production of at least one taxane or paclitaxel. There is also disclosed a novel bacterial taxane. The present invention also relates to the use of different biologically pure cultures of bacteria isolated from different species of Taxus, wherein the bacteria are able to biotransform pro-taxanes. There is also provided a process for improving taxanes and paclitaxel production of taxanes and paclitaxel producing bacteria which include culturing bacteria in the presence of a mutagenic agent for a period a time sufficient to allow mutagenesis.Type: GrantFiled: December 22, 1997Date of Patent: February 29, 2000Assignee: BCM Developpement, Inc.Inventors: Michel Page, Nathalie Landry, Maurice Boissinot, Marie-Claude Helie, Mario Harvey, Martin Gagne
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Patent number: 6028206Abstract: The present invention relates to an improved process for the production of important taxol analogues 10-deacetyl taxol A,B and C of the formula (2) ##STR1## R=C.sub.6 H.sub.5 (10 deacetyl taxol A) =CH.sub.3 C.dbd.CHCH.sub.3 (10-deacetyl taxol B)=C.sub.5 H.sub.11 (10-deacetyl taxol C)where R represent C.sub.6 H.sub.5 (10-deacetyl taxol A) or, CH.sub.3 C.dbd.CHCH.sub.3 (10-deacetyl taxol B) or, C.sub.5 H.sub.11 (10-deacetyl taxol C) which comprises (a) dissolving the taxol analogues 7-xylosyl-10-deacetyl taxol A,B,C of the formula (1) ##STR2## R=C.sub.6 H.sub.5 (10 deacetyl taxol A) =CH.sub.3 C.dbd.CHCH.sub.3 (10-deacetyl taxol B)=C.sub.5 H.sub.11 (10-deacetyl taxol C)where R represents C.sub.6 H.sub.5 (taxol analogue A or xyloside A), or CH.sub.3 C.dbd.CHCH.sub.3 (taxol analogue B or xyloside B) or C.sub.5 H.sub.11 (taxol analogue C or xyloside C) in a polar solvent (b) reacting the resultant solution with periodate for 20-40 hours at 20-40.degree. C.Type: GrantFiled: March 5, 1999Date of Patent: February 22, 2000Assignee: Council of Scientific and Industrial ResearchInventors: Sunil Kumar Chattopadhyay, Ram Prakash Sharma, Sushil Kumar
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Patent number: 6028205Abstract: Taxane derivatives having alternative C2 substituents.Type: GrantFiled: December 8, 1997Date of Patent: February 22, 2000Assignee: Florida State UniversityInventors: Robert A. Holton, Chunlin Tao
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Patent number: 6022938Abstract: Isocyanato compounds with capped, isocyanate-reactive groups are those of the formula I ##STR1## where R.sup.1 and R.sup.2 are hydrogen, C.sub.1 -C.sub.10 -alkyl, C.sub.6 -C.sub.10 -aryl or C.sub.7 -C.sub.10 -aralkyl or together form C.sub.3 -C.sub.10 -alkanediyl,X and Y are --O--, --S-- or ##STR2## where R.sup.4 is hydrogen, C.sub.1 -C.sub.20 -alkyl which is uninterrupted or interrupted by oxygen atoms in ether function, or is C.sub.6 -C.sub.10 -aryl or C.sub.7 -C.sub.10 -aralkyl,R.sup.3 is C.sub.1 -C.sub.10 -alkanediyl which together with --X--CR.sup.1 R.sup.2 --Y-- forms a 4-7-membered ring,in which either one hydrogen in R.sup.3 or the radical R.sup.4 in ##STR3## is replaced by an allophanate group R.sup.Ia ##STR4## in which R.sup.5 is a divalent aliphatic, alicyclic, araliphatic or aromatic C.sub.2 -C.sub.20 hydrocarbon unit,R.sup.6 is a single bond or a divalent aliphatic, alicyclic, araliphatic or aromatic C.sub.1 -C.sub.20 hydrocarbon unit or a mono- or poly(C.sub.2 -C.sub.Type: GrantFiled: June 18, 1998Date of Patent: February 8, 2000Assignee: Basf AktiengesellschaftInventors: Bernd Bruchmann, Hans Renz, Gunter Mohrhardt
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Patent number: 6022985Abstract: Process for the preparation of 4-acetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1,7.beta., 10.beta.-trihydroxy-9-oxo-tax-11-en-13.alpha.-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate trihydrate, characterized in that the 4-acetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1,7.beta.,10.beta.-trihydro xy-9-oxo-tax-11-en-13.alpha.-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate is crystallized from a mixture of water and an aliphatic alcohol containing 1 to 3 carbon atoms, and then the product obtained is dried under defined conditions of temperature, pressure and humidity.Type: GrantFiled: April 25, 1997Date of Patent: February 8, 2000Assignee: Rhone-Poulenc Rorer S.A.Inventors: Jean-Rene Authelin, Jacques Doveze, Elie Fouque, Bernadette Mandard, Isabelle Taillepied
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Patent number: 6020507Abstract: 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.Type: GrantFiled: February 18, 1999Date of Patent: February 1, 2000Assignee: Bristol-Myers Squibb CompanyInventor: Francis S. Gibson
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Patent number: 6018073Abstract: Taxane derivatives having an alkoxy, alkenoxy or aryloxy substituted C13 side chain.Type: GrantFiled: December 17, 1997Date of Patent: January 25, 2000Assignee: Florida State UniversityInventors: Robert A. Holton, Ki-byung Chai, Hamid Idmoumaz, Hossain Nadizadeh, Kasthuri Rengan, Yukio Suzuki, Chunlin Tao
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Patent number: 6015914Abstract: Provided is a compound having an oxetanyl group and represented by the following formula: ##STR1## wherein R.sub.1 represents a methyl group or an ethyl group and R.sub.2 represents a hydrogen atom, a halogen atom, a straight or branched chain alkyl group of 1-5 carbon atoms, an unsubstituted or substituted phenyl group, an unsubstituted or substituted phenoxymethyl group, an unsubstituted or substituted phenoxypropyl group or an unsubstituted or substituted phenyl group. A process for producing the compound and a curing composition comprising the compound and a cationic polymerization initiator are also provided.Type: GrantFiled: January 20, 1998Date of Patent: January 18, 2000Assignee: Toagosei, Co., Ltd.Inventors: Hiroshi Sasaki, Akira Kuriyama
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Patent number: 6013493Abstract: Taxol is produced from taxol-producing micro-organisms. Methods of obtain the taxol-producing microorganisms are described. Radioactive labelled taxol products and methods for use of the radioactive labelled taxol and for the treatment of leukemia and cancer cells are described.Type: GrantFiled: November 26, 1997Date of Patent: January 11, 2000Assignee: The Research and Development Institute at Montana State UniversityInventors: Andrea Stierle, Donald Stierle, Gary Strobel
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Patent number: 6011056Abstract: Taxane derivatives having alternative C9 substituents.Type: GrantFiled: June 5, 1995Date of Patent: January 4, 2000Assignee: Florida State UniversityInventors: Robert A. Holton, Ki-byung Chai, Yukio Suzuki
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Patent number: 6008385Abstract: A method for purifying taxoids (Taxotere, 10-deacetylbaccatin III) by centrifugal partition chromatography.Type: GrantFiled: August 20, 1997Date of Patent: December 28, 1999Assignee: Rhone-Poulenc Rorer S.A.Inventors: Andre Durand, Alain Gerbaud, Rodolphe Margraff
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Patent number: 6005138Abstract: Taxane derivatives having a 3' butenyl substituted C13 side chain.Type: GrantFiled: December 12, 1997Date of Patent: December 21, 1999Assignee: Florida State UniversityInventors: Robert A. Holton, Ki-byung Chai, Hossain Nadizadeh
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Patent number: 6005120Abstract: The synthesis of taxol and other tricyclic and tetracyclic taxanes.Type: GrantFiled: January 2, 1997Date of Patent: December 21, 1999Assignee: Florida State UniversityInventors: Robert A. Holton, Carmen Somoza, Hyeong Baik Kim, Mitsuru Shindo, Ronald J. Biediger, P. Douglas Boatman, Chase Smith, Feng Liang, Krishna Murthi
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Patent number: 6002025Abstract: Taxanes are purified by chromatographic separation using a phenylalkyl chromatographic resin, wherein the alkyl portion of the phenylalkyl is a C.sub.4 -C.sub.10 moiety. Taxanes such as paclitaxel, 10-deacetyltaxol, 7-epi-taxol, cephalomannine, baccatin III, baccatin V, 7-epi-DAB, 10-deactylbaccatin III ("DAB") and 9-dihydro-13-acetylbaccatin III ("DHB") and others may be purified. In accordance with the invention, taxanes are separated from each other and from other impurities common to crude taxane samples.Type: GrantFiled: February 24, 1999Date of Patent: December 14, 1999Assignee: BCM Developement Inc.Inventors: Michel Page, Marie-Josee Perron
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Patent number: 6002022Abstract: A process for the preparation of 4,10-diacetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1,7.beta.-dihydroxy-9- oxo-tax-11-en-13.alpha.-yl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropionate trihydrate by crystallization from a water/alcohol solution.Type: GrantFiled: July 24, 1997Date of Patent: December 14, 1999Assignee: Rhone-Poulenc Rorer S.A.Inventors: Jean-Rene Authelin, Eric Didier, Franck Leveiller, Isabelle Taillepied
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Patent number: 6002024Abstract: Novel process for isolation of 14.beta.-hydroxy 10-deacetyl baccatin-III (14.beta.-OH-DAB) on a commercial scale from plant extract by solvent crystallization without employing chromatographic separation.Type: GrantFiled: December 15, 1998Date of Patent: December 14, 1999Assignee: Dabur Research FoundationInventors: Sunder Ramadoss, Anand Vardhan
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Patent number: 6002023Abstract: The present invention relates to 2-debenzoyl-2-acyl taxol derivatives, analogues thereof and methods for making same.Compounds of the present invention include compounds having the general formula: ##STR1## wherein R.sub.1 is an alkyl or substituted alkyl; R.sub.2 is selected from the group consisting of H and C(O)R.sub.a ; R.sub.3 is selected from the group consisting of H, protecting groups, R.sub.b, and C(O)R.sub.b ; R.sub.4 is selected from the group consisting of H and C(O)R.sub.c, and wherein R.sub.a, R.sub.b, and R.sub.c are independently selected from the group consisting of alkyls, substituted alkyls, alkenyls, alkynyls, aryls, and substituted aryls; provided that R.sub.a is other than phenyl and 3-hydroxyphenyl.Type: GrantFiled: October 15, 1997Date of Patent: December 14, 1999Assignee: Virginia Tech Intellectural Properties, Inc.Inventors: David G. I. Kingston, Ashok Gopal Chaudhary, Milind Moreshwar Gharpure, John Matthew Rimoldi, A.A. Leslie Gunatilaka
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Patent number: 5998656Abstract: Taxane derivatives having alternative C10 substituents.Type: GrantFiled: December 4, 1997Date of Patent: December 7, 1999Assignee: Florida State UniversityInventors: Robert A. Holton, Ki-byung Chai
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Patent number: 5994576Abstract: Taxane derivatives having alternative C7 substituents.Type: GrantFiled: December 8, 1997Date of Patent: November 30, 1999Assignee: Florida State UniversityInventors: Robert A. Holton, Ki-byung Chai