Sulfur Or Halogen Attached Directly Or Indirectly To The Hetero Ring By Nonionic Bonding Patents (Class 549/511)
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Patent number: 5955621Abstract: The present invention provides new sources of taxanes and other metabolites from members of the order Coniferales that are not in the genus Taxus.Type: GrantFiled: April 24, 1997Date of Patent: September 21, 1999Assignee: The Regents of the University of CaliforniaInventors: Don J. Durzan, Frank Ventimiglia
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Patent number: 5948919Abstract: 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, celphalomanninne and various analogs, including photoaffinity labeling candidates.Type: GrantFiled: June 7, 1995Date of Patent: September 7, 1999Assignees: NaPro BioTherapeutics, Inc., Bryn Mawr CollegeInventors: Nicholas J. Sisti, Charles S. Swindell, Madhavi C. Chander
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Patent number: 5939567Abstract: 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: December 10, 1997Date of Patent: August 17, 1999Assignee: The Liposome Company, Inc.Inventors: Eric Mayhew, J. Craig Franklin, Suresh Bhatia, Paul A. Harmon, Andrew S. Janoff
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Patent number: 5939566Abstract: An efficient protocol for the synthesis of taxol, taxol analogs and their intermediates is described. The process includes 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, celphalomanninne and various analogs, including photoaffinity labeling candidates.Type: GrantFiled: June 7, 1995Date of Patent: August 17, 1999Assignee: Bryn Mawr CollegeInventors: Charles S. Swindell, Nancy Krauss
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Patent number: 5917062Abstract: The semisynthesis of paclitaxel and its analogs using new intermediates which are derivatives of 10-deacetyl-baccatin III, as well as to a method for preparing these derivatives. These novel derivatives have alkyl carbonate or alkyl carbonyl substituents in the 7 position.Type: GrantFiled: November 21, 1997Date of Patent: June 29, 1999Assignee: Indena S.p.AInventor: Ezio Bombardelli
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Patent number: 5916783Abstract: Taxol is produced from taxol-producing microorganisms. Methods of obtaining he 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: June 29, 1999Assignee: The Research and Development Institute at Montana State UniversityInventors: Andrea Stierle, Donald Stierle, Gary Strobel
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Patent number: 5914411Abstract: A method of acylating 10-deacetylbaccatin III at the C-10 position over the C-7 hydroxy position thereof to produce baccatin IIII is accomplished first by dissolving 10-deacetylbaccatin III 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. The result is baccatin III in solution. 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 baccatin III.Type: GrantFiled: January 21, 1998Date of Patent: June 22, 1999Assignee: NaPro BioTherapeutics, Inc.Inventors: Nicholas J. Sisti, Jan Zygmunt, Herbert R. Brinkman, Madhavi C. Chander, Xian Liang, James D. McChesney
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Patent number: 5912263Abstract: Taxane derivatives modified at 13-position of the taxane derivative skeleton (taxol numbering) of formula (I), wherein R, R.sub.a, R.sub.b, R.sub.c, R.sub.1, R.sub.2, R.sub.3 are appropriate organic residues can be antitumor agents.Type: GrantFiled: November 5, 1997Date of Patent: June 15, 1999Assignee: Pharmacia S.p.A.Inventors: Maria Menichincheri, Walter Ceccarelli, Marina Ciomei, Domenico Fusar Bassini, Nicola Mongelli, Ermes Vanotti
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Patent number: 5912264Abstract: The present invention concerns novel taxane derivatives, their use as antitumor agents, and pharmaceutical formulations.Type: GrantFiled: February 2, 1998Date of Patent: June 15, 1999Assignee: Bristol-Myers Squibb CompanyInventors: Mark D. Wittman, John F. Kadow
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Patent number: 5908759Abstract: Taxol is produced from taxol-producing microorganisms. Methods of obtaining he 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: June 1, 1999Assignee: The Research and Development Institute at Montana State UniversityInventors: Andrea Stierle, Donald Stierle, Gary Strobel
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Patent number: 5907042Abstract: The semisynthesis of paclitaxel and its analogs using new intermediates which are derivatives of 10-deacetyl-baccatin III, as well as to a method for preparing these derivatives. These novel derivatives have alkyl carbonate or alkyl carbonyl substituents in the 7 position.Type: GrantFiled: September 30, 1998Date of Patent: May 25, 1999Assignee: Indena S.p.A.Inventor: Ezio Bombardelli
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Patent number: 5906990Abstract: The present invention relates to novel taxoids of general formula: ##STR1## in which: Z represents a hydrogen atom or a radical of general formula: ##STR2##Type: GrantFiled: October 10, 1997Date of Patent: May 25, 1999Assignee: Rhone-Poulenc Rorer S.A.Inventors: Herve Bouchard, Alain Commercon
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Patent number: 5902822Abstract: The present invention concerns novel paclitaxel derivatives, their use as antitumor agents, and pharmaceutical formulations.Type: GrantFiled: February 18, 1998Date of Patent: May 11, 1999Assignee: Bristol-Myers Squibb CompanyInventors: Jerzy Golik, Dolatrai M. Vyas
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Patent number: 5900367Abstract: The present invention relates to a rapid and simple method for mass production of taxol from the cell culture of Taxus genus plant with a high purity and recovery. The method for mass production of taxol from Taxus genus plant of the present invention, comprises the steps of: (i) organic solvent extraction of biomass from Taxus genus plant to obtain a crude extract; (ii) synthetic adsorbent treatment of the crude extract and filtration to give filtrate; (iii) addition of hexane to the filtrate to precipitate crude taxol; (iv) fractional precipitation of the crude taxol in a mixture of alcohol and water and vacuum drying the precipitate to obtain taxol powder; and, (v) high performance liquid chromatography of the taxol powder. According to the method of the present invention, taxol of over 99% purity can be simply obtained from Taxus genus plant with a high recovery of over 90%.Type: GrantFiled: May 28, 1996Date of Patent: May 4, 1999Assignee: Samyang Genex Co., Ltd.Inventors: Seung-Suh Hong, Bong-Kyu Song, Jin-Hyun Kim, Chang-Bae Lim, Hyun-Soo Lee, Kwang-Wook Kim, In-Seon Kang, Hung-Bok Park
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Patent number: 5892064Abstract: A chemiluminescent assay method and compositions are described which use a dialkyl-substituted dioxetane which is deprotected to trigger a chemiluminescent reaction. Chemiluminescent 1,2-dioxetane compounds substituted on the dioxetane ring with two nonspirofused alkyl groups which can be triggered by a reagent to generate light are disclosed. Dialkyl-substituted dioxetanes are useful for the detection of triggering agents including enzymes. The enzyme may be present alone or linked to a member of a specific binding pair in an immunoassay, DNA probe assay or other assay where the enzyme is bound to a reporter molecule.Type: GrantFiled: November 26, 1997Date of Patent: April 6, 1999Assignee: Lumigen, Inc.Inventors: Arthur Paul Schaap, Hashem Akhavan-Tafti
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Patent number: 5892063Abstract: An antitumor compound of formula (5) ##STR1## in which R is Ac or H, and R.sub.1, R.sub.2 is an alkyl group such as Me, Et, Pr, i-Pr, n-Bu or t-Bu, R.sub.3 is H; R.sub.1 and R.sub.2 and R.sub.3 are H; R.sub.1 is an alkyl group such as Me, Et, Pr, i-Pr, n-Bu or t-Bu, R.sub.2, R.sub.3 is H; R.sub.1 and R.sub.3 are H, R.sub.2 is an alkyl group such as Me, Et, Pr, i-Pr, n-Bu or t-Bu; R.sub.1 is H, R.sub.2 and R.sub.3 are an alkyl group such as Me, Et, Pr, i-Pr, n-Bu or t-Bu; R.sub.1 and R.sub.2 and R.sub.3 are an alkyl group Me, Et, Pr, i-Pr, n-Bu or t-Bu. Me is an abbreviation for methyl, Et is ethyl, Pr is propyl, i-Pr is isopropyl, n-Bu is n-butyl, and t-Bu is tert-butyl. Also provided by the invention is a one step method of preparing a compound of formula (5) whereby a taxane having a tiglate group attached to the side chain is contacted with an oxidizing reagent resulting in the formation of an epoxide having antitumor activity.Type: GrantFiled: May 21, 1997Date of Patent: April 6, 1999Assignee: Hauser, Inc.Inventors: Qun Y. Zheng, Christopher K. Murray, Randall J. Daughenbaugh
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Patent number: 5889043Abstract: The present invention relates to new taxoids of general formula: ##STR1## in which: Z represents a hydrogen atom or a radical of general formula: ##STR2##Type: GrantFiled: September 26, 1997Date of Patent: March 30, 1999Assignee: Rhone-Poulenc Rorer S.A.Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commer.cedilla.on
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Patent number: 5886199Abstract: The present invention is to provide for a process for producing 3-chloromethyl-3-alkyloxetanes from a 1,1-bis(chloromethyl)-1-hydroxymethylalkane or its carboxylate ester through a dehydrogen chloride reaction or a deacid chloride reaction in an aqueous solution or suspension of an alkaline compound. The reaction is conducted, either in the presence of a phase transfer catalyst or an anion exchange resin having an ammonium group, or, while distilling the formed 3-chloromethyl-3-alkyloxetane out azeotropically with water. The invention enables one to produce 3-chloromethyl-3-alkyloxetanes within a shorter period of time and with a higher yield, and thus the process is much advantageous and useful from the industrial points of view.Type: GrantFiled: January 22, 1998Date of Patent: March 23, 1999Assignee: Toagosei Co., Ltd.Inventors: Naokazu Ito, Toshiro Hirose
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Patent number: 5880131Abstract: High molecular weight, water-soluble prodrugs of the formula: ##STR1## wherein: D is a biologically active moiety;M is X or Q;X is an electron withdrawing group;Q is a moiety containing a free electron pair positioned five or six atoms from Y';Y and Y' are oxygen or sulfur;R is a polyalkylene oxide; andZ is OH, C.sub.1-4 all moieties or ##STR2## are disclosed. In preferred embodiments, the prodrugs contain a polyethylene glycol having a molecular weight of at least about 20,000.Type: GrantFiled: September 29, 1995Date of Patent: March 9, 1999Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Annapurna Pendri
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Patent number: 5874595Abstract: 10-Deacetylbaccatin III is selectively acylated to baccatin III and derivatives thereof in high yield with anhydrides (e.g. acetic anhydride), catalysed by Lewis acids. Extremely effective catalysts in this reaction are compounds of the formula ML.sub.x wherein M is a rare earth metal and L is a anion, preferably a strong electron withdrawing counterion such as triflate.Type: GrantFiled: May 21, 1997Date of Patent: February 23, 1999Assignee: Pharmachemie B.V.Inventors: Eric Wilhelmus Petrus Damen, Johan Wilhelm Scheeren, Dick de Vos
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Patent number: 5871979Abstract: The present invention relates to a method for mass production of taxol by semi-continuous culture of Taxus genus plant with a high yield. According to the present invention, taxol can be prepared with a high yield, by employing semi-continuous culture of Taxus genus plant cell, which comprises: (i) inoculating Taxus genus plant cell on a medium containing 1 to 10% (w/v) sugar, and incubating it; and, (ii) transferring 1/10 to 1/2 volume of the culture obtained in the step (i) to a fresh medium and repeating the step (i), adding 1 to 10% (w/v) sugar to the remnant culture and incubating to the time of maximum production of taxol.Type: GrantFiled: May 28, 1996Date of Patent: February 16, 1999Assignee: Samyang Genex Co., Ltd.Inventors: Hyung-Kyoon Choi, Tom Lee Adams, Roy William Stahlhut, Sang-Ic Kim, Jeong-Hwan Yun, Bong-Kyu Song, Jin-Hyun Kim, Jun-Seog Song, Seung-Suh Hong, Hyun-Soo Lee
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Patent number: 5869680Abstract: This invention relates to a method of preparing taxane derivatives of general formula (I) by esterification of protected baccatine III or 10-deacetylbaccatine III by means of an acid of general formula (VII), elimination of protection groupings of the ester obtained, and acylation of the amine function of the side chain. In formulae (I) and (VII): Ar stands for aryl, R is hydrogen or acetyl, R.sub.1 is benzoyl or R.sub.2 -CO--O- in which R.sub.2 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl, R.sub.3 and R.sub.4 may be the same or different and represent hydrogen, alkyl, alkenyl, aralkyl, aryl or alkoxy, and R.sub.5 is an alkyl radical substituted by one or more chlorine atoms (2,2,2-trichloroethyl, 2-trichloromethylisopropyl).Type: GrantFiled: August 8, 1997Date of Patent: February 9, 1999Assignee: Rhone-Poulenc Rorer, S.A.Inventors: Jean-Manuel Mas, Viviane Massonneau
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Patent number: 5861302Abstract: 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: June 10, 1994Date of Patent: January 19, 1999Assignee: The Research and Development Institute at Montana State UniversityInventors: Andrea Stierle, Donald Stierle, Gary Strobel
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Patent number: 5861515Abstract: This invention relates to a method of preparing taxane derivatives of formula (VIII) by esterification of protected baccatin III or 10-deacetylbaccatin III by means of an acid of formula (VII), elimination of protection groupings and acylation of the amine function of the side chain. In formulae (VIII) and (VII): Ar stands for aryl, R.sub.3 is a trihalomethyl radical or phenyl substituted by a trihalomethyl radical, R.sub.4 is a hydrogen atom or is the same as R.sub.1. G.sub.1 and G.sub.2 are hydroxy protecting groups.Type: GrantFiled: October 31, 1997Date of Patent: January 19, 1999Assignee: Rhone-Poulenc Rorer S.A.Inventors: Alain Commercon, Eric Didier, Elie Fouque
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Patent number: 5856532Abstract: A process has been developed for production of taxols A, B, C with high yields from 7-xylosyl-10-deacetyl taxol A (taxol analogue A or, xyloside A), 7-xylosyl-10-deacetyl-taxol B (taxol analogue B or xyloside B), 7-xylosyl-10-deacetyl--taxol C (taxol analogue C or xyloside C), which comprises (i) isolating the taxol analogues A, B, C form the stembark of Taxus wallichiana by an improved process devoiding of solvent partitioning step, (ii) treating the isolated taxol analogues A, B, C with periodates in an acid free polar solvent medium to cleave the diol into dialdehyde at ambient temperature, (iii) reducing the dialdehyde solution with borohydride in a polar solvent--acetic acid medium at 0.degree.-40.degree. C. into an acetal, (iv) acidifying the resultant acetal with a mixture of mineral acid-polar solvent at 0.degree.-40.degree. C. into intermediate product 10-deacetyl taxols A, B, C, (V) reacting 10-deacetyl taxols A or B or C with a silane in presence of a base at 20.degree.-40.degree. C.Type: GrantFiled: August 12, 1997Date of Patent: January 5, 1999Assignee: Council of Scientific & Industrial ResearchInventors: Sunil Kumar Chattopadhyay, Ram Prakash Sharma, Sushil Kumar, Kunnath Padmanabhan Madhusudanan
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Patent number: 5854278Abstract: Provided are novel paclitaxel analogues which are selectively chlorinated stereospecific derivatives of cephalomannine and 7-epi-cephalomannine having paclitaxel-like antitumor efficacy, methods for their preparation and methods for treating tumors with these compounds.Type: GrantFiled: May 29, 1996Date of Patent: December 29, 1998Assignee: Xechem International, Inc.Inventors: Ramesh C. Pandey, Luben K. Yankov, Raghu Nair, Alex Poulev
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Patent number: 5847170Abstract: New taxoids of general formula (I): ##STR1## their preparation and pharmaceutical compositions containing them, and the new products of general formula (I) in which Z represents a radical of general formula (II): ##STR2## display noteworthy antitumour and antileukaemic properties.Type: GrantFiled: March 26, 1996Date of Patent: December 8, 1998Assignee: Rhone-Poulenc Rorer, S.A.Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commer.cedilla.on
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Patent number: 5840929Abstract: The present invention concerns novel paclitaxel derivatives, their use as antitumor agents, and pharmaceutical formulations.Type: GrantFiled: September 9, 1996Date of Patent: November 24, 1998Assignee: Bristol-Myers Squibb CompanyInventor: Shu-Hui Chen
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Patent number: 5840748Abstract: Provided are antineoplastic derivatives by a process of selective halogenation of side chains of unsaturated taxanes; more particularly, the process involves the use of halogens, particularly bromine, which is easily added to the side chain double bond of cephalomannine, leaving paclitaxel unchanged, and wherein diastereomeric mixtures of 2", 3"-dibromocephalomannine display high activity against: Leukemia cell line HL-60 (TB); Non-Small Cell Lung Cancer line NCI-H522; Colon Cancer cell lines COLO 205 and HT 29; CNS Cancer cell lines SF-539 and SNB-75; Ovarian Cancer Cell line OVCAR-3; Renal Cancer cell line RXF-393; and Breast Cancer cell lines MCF7, MDA-MB-231/ATCC, HS 578T, MDA-MB-435 and MDA-N.Type: GrantFiled: December 13, 1995Date of Patent: November 24, 1998Assignee: Xechem International, Inc.Inventors: Luben K. Yankov, Ramesh C. Pandey
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Patent number: 5840930Abstract: Provided are antineoplastic derivatives by a process of selective halogenation of side chains of unsaturated taxanes; more particularly, the process involves the use of halogens, particularly bromine, which is easily added to the side chain double bond of cephalomannine, leaving paclitaxel unchanged, and wherein diastereomeric mixtures of 2", 3"-dibromocephalomannine display high activity against: Leukemia cell line HL-60 (TB); Non-Small Cell Lung Cancer line NCI-H522; Colon Cancer cell lines COLO 205 and HT 29; CNS Cancer cell lines SF-539 and SNB-75; Ovarian Cancer Cell line OVCAR-3; Renal Cancer cell line RXF-393; and Breast Cancer cell lines MCF7, MDA-MB-231/ATCC, HS 578T, MDA-MB-435 and MDA-N.Type: GrantFiled: November 4, 1996Date of Patent: November 24, 1998Assignee: Xechem International, Inc.Inventors: Luben K. Yankov, Ramesh C. Pandey
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Patent number: 5840931Abstract: This invention relates to compounds of the formula (I), preparation thereof, and pharmaceutical compositions containing them: ##STR1## wherein: R.sub.a is hydrogen, hydroxyl, alkoxy, acyloxy, or an alkoxyacetoxy radical; R.sub.b is hydrogen; or R.sub.a and R.sub.b, together with the carbon atom to which they are attached, form a ketone function; Z represents a hydrogen atom or a radical of formula (II): ##STR2## in which: R.sub.1 represents an optionally substituted benzoyl, thenoyl, furoyl, or R.sub.2 --O--CO-- radical where R.sub.2 is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, or an optionally substituted phenyl or heterocyclic radical; R.sub.3 is an aromatic heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, or a phenyl or naphthyl radical; R.sub.4 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, aryl, or heterocyclic radical; and R.sup.5 is an optionally substituted cycloalkenyl, alkyl, alkenyl, alkynyl, or cycloalkyl radical.Type: GrantFiled: April 24, 1997Date of Patent: November 24, 1998Assignee: Rhone-Poulenc Rorer S.A.Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commer.cedilla.on, Corinne Terrier, Martine Zucco
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Patent number: 5831102Abstract: Enzymatically cleavable chemiluminescent 1,2-dioxetane compounds capable of producing light energy when decomposed, substantially stable at room temperature before a bond by which an enzymatically cleavable labile substituent thereof is intentionally cleaved, are disclosed. These compounds can be represented by the formula: ##STR1## wherein: X and X.sup.1 each represent, individually, hydrogen, a hydroxyl group, a halo substituent, an unsubstituted lower alkyl group, a hydroxy (lower) alkyl group, a halo (lower) alkyl group, a phenyl group, a halophenyl group, an alkoxyphenyl group, a hydroxyalkoxy group, a cyano group or an amide group, with at least one of X and X.sup.1 being other than hydrogen; andR.sub.1 and R.sub.2, individually or together, represent an organic substituent that does not interfere with the production of light when the dioxetane compound is enzymatically cleaved and that satisfies the valence of the dioxetane compound's 4-carbon atom, with the provisos that if R.sup.1 and R.sub.Type: GrantFiled: February 8, 1996Date of Patent: November 3, 1998
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Patent number: 5824701Abstract: Taxane-based compositions of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of aryls, substituted aryls, aralkyls, substituted aralkyls, alkyls and substituted alkyls;R.sub.2 is an aryl or substituted aryl, preferably phenyl;R.sub.3 is H, a C.sub.1-10 alkoxy, SiEt.sub.3 or ##STR2## Y is O or S; (n) is zero or a positive integer;X is oxygen, S, SO.sub.2 or NL, where L is selected from the group consisting of H, C.sub.1-8 alkyls, aryls and aralkyls;R.sub.4 is H or an aroyl of the formula: ##STR3## wherein Ar is an aromatic, substituted aromatic or heteroaromatic group; R.sub.5 is H, CH.sub.3 CO or a substituted acetic acid derivative;Z is H or OR.sub.6 where R.sub.6 is selected from the group consisting of H, C.sub.1-8 alkyls, C.sub.1-8 substituted alkyls, C.sub.1-8 aralkyls, substituted aryls, aralkyls, substituted aralkyls, C.sub.1-10 alkoxy, SiEt.sub.3, ##STR4## P is O or OH; R.sub.8 is one of H, S(CH.sub.3).sub.3, Si(C.sub.2 H.sub.5).sub.3, CH.sub.Type: GrantFiled: February 3, 1997Date of Patent: October 20, 1998Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Annapurna Pendri
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Patent number: 5821263Abstract: This invention provides a novel series of taxane derivatives which are characterized by the C3' nitrogen bearing one or two sulfur substituents. The new derivatives are antitumor agents useful in the treatment of such cancers as ovarian, breast, lung, gastric, colon, head and neck, melanoma and leukemia.Type: GrantFiled: July 29, 1997Date of Patent: October 13, 1998Assignee: Bristol-Myers Squibb CompanyInventors: Paul M. Scola, Dolatrai M. Vyas
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Patent number: 5821363Abstract: This invention provides 7-deoxy-.DELTA..sup.12,13 -iso-taxol of formula (I) which are useful for the treatment of the same cancers for which taxol has been shown active.Type: GrantFiled: July 23, 1996Date of Patent: October 13, 1998Assignee: Pharmacia & Upjohn CompanyInventors: Nancy A. Wicnienski, Robert C. Kelly, Peter G. M. Wuts
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Patent number: 5814658Abstract: New taxoids of general formula (I), their preparation, and pharmaceutical compounds containing them. ##STR1## In general formula (I), for example, Ar represents an aryl radical,R represents an alkoxyacetyl radical,R.sub.1 represents a benzoyl radical or a radical of formula R.sub.2 --O--CO-- in which R.sub.2 represents an optionally substituted alkyl radical, an alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical.The new products of general formula (I) have a remarkable antitumor activity.Type: GrantFiled: June 7, 1995Date of Patent: September 29, 1998Assignee: Rhone-Poulenc Rorer S.A.Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commercon
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Patent number: 5811452Abstract: The present invention is directed to novel taxoids possessing strong reversing activities for drug-resistance associated with anti-cancer agents, the preparation of these reversal agents and pharmaceutical compositions thereof. The new taxoids of the present invention have the formula (I).Type: GrantFiled: January 8, 1997Date of Patent: September 22, 1998Assignees: The Research Foundation of State University of New York, Health Research IncInventors: Iwao Ojima, Ralph J. Bernacki
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Patent number: 5807977Abstract: This application is directed to novel fluorinated polymers and prepolymers derived from mono-substituted oxetane monomers having fluorinated alkoxymethylene side-chains and the method of making these compositions. The mono-substituted fluorinated oxetane monomers having fluorinated alkoxymethylene side-chains are prepared in high yield by the reaction of a fluorinated alkoxides with either 3-halomethyl-3-methyloxetane premonomers or aryl sulfonate derivative of 3-hydroxymethyl-3-methyloxetane premonomers. Preparation of a mono-substituted 3-bromomethyl-3-methyloxetane premonomer via a simple, high yield process amenable to commercial scaleup is also disclosed. The fluorinated oxetane monomers of this invention can be readily homo/co-polymerized in the presence of a Lewis acid and polyhydroxy compounds to obtain hydroxy-terminated polyether prepolymers having fluorinated alkoxymethylene side chains.Type: GrantFiled: January 12, 1995Date of Patent: September 15, 1998Assignee: Aerojet General CorporationInventors: Aslam A. Malik, Thomas G. Archibald
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Patent number: 5808113Abstract: The invention relates to a process for converting Taxol A, B and C to Taxol primary amine which can then be easily and efficiently converted to Taxol A or docetaxel, thereby significantly increasing the yield of these products from biomass. The method includes the removal of the amide from the side-chain with Schwartz's reagent to form an imine, followed by the hydrolysis of the imine to the primary amine. The primary amine can then be converted to Taxol A or docetaxel. New Taxol imine compounds and primary amine salts have been formed by this process.Type: GrantFiled: May 7, 1997Date of Patent: September 15, 1998Assignee: Hauser, Inc.Inventors: Christopher K. Murray, Qun Y. Zheng, Xiaoqin Cheng, S. Kent Peterson
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Patent number: 5808102Abstract: 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 22, 1997Date of Patent: September 15, 1998Assignee: Bristol-Myers Squibb CompanyInventors: 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: 5807888Abstract: Provided are novel paclitaxel analogues, namely selectively brominated stereospecific derivatives of cephalomannine and 7-epi-cephalomannine having in vivo and in vitro paclitaxel-like antitumor efficacy, methods of preparation therefor and methods for treating tumors with these compounds.Type: GrantFiled: May 29, 1996Date of Patent: September 15, 1998Assignee: Xechem International, Inc.Inventors: Ramesh C. Pandey, Luben K. Yankov, Raghu Nair, Alex Pouley
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Patent number: 5801191Abstract: Novel taxoids are provided having enhanced water solubility and/or improved pharmacological properties as compared to paclitaxel. The subject taxoids comprise a functional group attached to a paclitaxel at the C-2' and/or C-7 position by a linking group. Functional groups present in the subject taxoids may be hydrophilic chains, groups capable of in vivo conversion to hydrophilic chains, targeting moieties capable of specifically binding with cellular receptors and water soluble polymers of at least 5 kD. The subject taxoids find use in the treatment of hosts suffering from a cellular proliferative disease.Type: GrantFiled: June 1, 1995Date of Patent: September 1, 1998Assignee: Biophysica FoundationInventors: Jerome C. Bressi, James G. Douglass, III, Allen Seligson, Milos Sovak
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Patent number: 5786489Abstract: 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: April 1, 1996Date of Patent: July 28, 1998Assignee: The Scripps Research InstituteInventors: Kyriacos C. Nicolaou, Philippe G. Nantermet, Rodney K. Guy, Hiroaki Ueno
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Patent number: 5777139Abstract: This invention relates to taxoids of the formula (I): a method for preparing these taxoids, and pharmaceutical compositions containing them. In formula (I), R is alkyl radical (1-6 carbon atoms), alkenyl (2-6 carbon atoms), alkynyl (2-6 carbon atoms), cycloalkyl (3-6 carbon atoms), cycloalkenyl (4-6 carbon atoms), phenyl, unsaturated heterocyclyl containing from 5 to 6 links, Z is a hydrogen atom or a radical of formula (II): ##STR1## wherein R.sub.1 is an optionally substituted benzoyl radical, thenoyl radical, furoyl radical, or a radical R.sub.2 --O--CO-- in which R.sub.2 is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, optionally substituted phenyl or heterocyclyl, and R.sub.3 is an alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, naphthyl or aromatic heterocyclic radical. The taxoids of formula (I) in which Z is a radical of formula (II) have remarkable antitumoral and antileukemic properties.Type: GrantFiled: December 6, 1996Date of Patent: July 7, 1998Assignee: Rhone-Poulenc Rorer S.A.Inventors: Herve Bouchard, Jean-Dominique Boureat, Alain Commer.cedilla.on
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Patent number: 5773461Abstract: The present invention concerns novel paclitaxel derivatives, their use as antitumor agents, and pharmaceutical formulations.Type: GrantFiled: June 4, 1997Date of Patent: June 30, 1998Assignees: Bristol-Myers Squibb Company, Virginia Tech Intellectual Properties, Inc.Inventors: Mark D. Wittman, Thomas J. Altstadt, John F. Kadow, David G. I. Kingston, Xian Liang
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Patent number: 5773464Abstract: The present invention concerns novel paclitaxel derivatives, their use as antitumor agents, and pharmaceutical formulations.Type: GrantFiled: August 29, 1997Date of Patent: June 30, 1998Assignee: Bristol-Myers Squibb CompanyInventors: Michael A. Walker, John F. Kadow
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Patent number: 5770745Abstract: 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, celphalomanninne and various analogs, including photoaffinity labeling candidates.Type: GrantFiled: December 15, 1994Date of Patent: June 23, 1998Assignee: Bryn Mawr CollegeInventors: Charles S. Swindell, Nancy Krauss
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Patent number: 5767282Abstract: A process of making taxane derivatives by reacting Baccatin III derivatives with an oxazolidine which contains a thioester substituent at the 4-position.Type: GrantFiled: February 20, 1997Date of Patent: June 16, 1998Assignee: Pharmacia & Upjohn S.p.A.Inventors: Cesare Gennari, Nicola Mongelli, Ermes Vanotti, Anna Vulpetti
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Patent number: 5767296Abstract: A novel taxol derivative having the formula (I), in which the 10-position is modified to have a carbon-carbon bond, is disclosed. The taxol derivative of the present invention has an antitumor activity.Type: GrantFiled: December 6, 1996Date of Patent: June 16, 1998Assignee: Daiichi Pharmaceutical Co., Ltd.Inventors: Hirofumi Terasawa, Tsunehiko Soga, Kiyoshi Nakayama
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Patent number: 5767297Abstract: A taxoid derivative wherein sugar is combined with any one of paclitaxel, docetaxel and 10-deacetyl-bacatin III via a spacer. A method of producing the taxoid derivative comprises protecting hydroxyl groups at specific position of paclitaxel or docetaxel by protective compound followed by reacting with tetrabenzyl acetyloxyglucoside, and then carrying out debenzyl and detriethylsilyl reactions. A method of producing the taxoid derivative comprises reacting paclitaxel or docetaxel with tetrabenzyl acetyloxyglucoside, and then carrying out debenzyl reaction.Type: GrantFiled: June 3, 1997Date of Patent: June 16, 1998Assignees: Ensuiko Sugar Refining Co., Ltd., Tadakatsu MANDAI, Kaken Pharmaceutical Co., Ltd.Inventors: Tadakatsu Mandai, Hiroshi Okumoto, Koji Hara, Katsuhiko Mikuni, Kozo Hara, Hiroki Hamada