Sulfur Or Halogen Attached Directly Or Indirectly To The Hetero Ring By Nonionic Bonding Patents (Class 549/511)
  • Patent number: 5955621
    Abstract: 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: Grant
    Filed: April 24, 1997
    Date of Patent: September 21, 1999
    Assignee: The Regents of the University of California
    Inventors: Don J. Durzan, Frank Ventimiglia
  • Patent number: 5948919
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: September 7, 1999
    Assignees: NaPro BioTherapeutics, Inc., Bryn Mawr College
    Inventors: Nicholas J. Sisti, Charles S. Swindell, Madhavi C. Chander
  • Patent number: 5939567
    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.
    Type: Grant
    Filed: December 10, 1997
    Date of Patent: August 17, 1999
    Assignee: The Liposome Company, Inc.
    Inventors: Eric Mayhew, J. Craig Franklin, Suresh Bhatia, Paul A. Harmon, Andrew S. Janoff
  • Patent number: 5939566
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: August 17, 1999
    Assignee: Bryn Mawr College
    Inventors: Charles S. Swindell, Nancy Krauss
  • Patent number: 5917062
    Abstract: 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: Grant
    Filed: November 21, 1997
    Date of Patent: June 29, 1999
    Assignee: Indena S.p.A
    Inventor: Ezio Bombardelli
  • Patent number: 5916783
    Abstract: 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: Grant
    Filed: November 26, 1997
    Date of Patent: June 29, 1999
    Assignee: The Research and Development Institute at Montana State University
    Inventors: Andrea Stierle, Donald Stierle, Gary Strobel
  • Patent number: 5914411
    Abstract: 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: Grant
    Filed: January 21, 1998
    Date of Patent: June 22, 1999
    Assignee: NaPro BioTherapeutics, Inc.
    Inventors: Nicholas J. Sisti, Jan Zygmunt, Herbert R. Brinkman, Madhavi C. Chander, Xian Liang, James D. McChesney
  • Patent number: 5912263
    Abstract: 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: Grant
    Filed: November 5, 1997
    Date of Patent: June 15, 1999
    Assignee: Pharmacia S.p.A.
    Inventors: Maria Menichincheri, Walter Ceccarelli, Marina Ciomei, Domenico Fusar Bassini, Nicola Mongelli, Ermes Vanotti
  • Patent number: 5912264
    Abstract: The present invention concerns novel taxane derivatives, their use as antitumor agents, and pharmaceutical formulations.
    Type: Grant
    Filed: February 2, 1998
    Date of Patent: June 15, 1999
    Assignee: Bristol-Myers Squibb Company
    Inventors: Mark D. Wittman, John F. Kadow
  • Patent number: 5908759
    Abstract: 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: Grant
    Filed: November 26, 1997
    Date of Patent: June 1, 1999
    Assignee: The Research and Development Institute at Montana State University
    Inventors: Andrea Stierle, Donald Stierle, Gary Strobel
  • Patent number: 5907042
    Abstract: 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: Grant
    Filed: September 30, 1998
    Date of Patent: May 25, 1999
    Assignee: Indena S.p.A.
    Inventor: Ezio Bombardelli
  • Patent number: 5906990
    Abstract: 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: Grant
    Filed: October 10, 1997
    Date of Patent: May 25, 1999
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: Herve Bouchard, Alain Commercon
  • Patent number: 5902822
    Abstract: The present invention concerns novel paclitaxel derivatives, their use as antitumor agents, and pharmaceutical formulations.
    Type: Grant
    Filed: February 18, 1998
    Date of Patent: May 11, 1999
    Assignee: Bristol-Myers Squibb Company
    Inventors: Jerzy Golik, Dolatrai M. Vyas
  • Patent number: 5900367
    Abstract: 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: Grant
    Filed: May 28, 1996
    Date of Patent: May 4, 1999
    Assignee: 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
  • Patent number: 5892064
    Abstract: 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: Grant
    Filed: November 26, 1997
    Date of Patent: April 6, 1999
    Assignee: Lumigen, Inc.
    Inventors: Arthur Paul Schaap, Hashem Akhavan-Tafti
  • Patent number: 5892063
    Abstract: 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: Grant
    Filed: May 21, 1997
    Date of Patent: April 6, 1999
    Assignee: Hauser, Inc.
    Inventors: Qun Y. Zheng, Christopher K. Murray, Randall J. Daughenbaugh
  • Patent number: 5889043
    Abstract: 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: Grant
    Filed: September 26, 1997
    Date of Patent: March 30, 1999
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commer.cedilla.on
  • Patent number: 5886199
    Abstract: 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: Grant
    Filed: January 22, 1998
    Date of Patent: March 23, 1999
    Assignee: Toagosei Co., Ltd.
    Inventors: Naokazu Ito, Toshiro Hirose
  • Patent number: 5880131
    Abstract: 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: Grant
    Filed: September 29, 1995
    Date of Patent: March 9, 1999
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Annapurna Pendri
  • Patent number: 5874595
    Abstract: 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: Grant
    Filed: May 21, 1997
    Date of Patent: February 23, 1999
    Assignee: Pharmachemie B.V.
    Inventors: Eric Wilhelmus Petrus Damen, Johan Wilhelm Scheeren, Dick de Vos
  • Patent number: 5871979
    Abstract: 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: Grant
    Filed: May 28, 1996
    Date of Patent: February 16, 1999
    Assignee: 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
  • Patent number: 5869680
    Abstract: 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: Grant
    Filed: August 8, 1997
    Date of Patent: February 9, 1999
    Assignee: Rhone-Poulenc Rorer, S.A.
    Inventors: Jean-Manuel Mas, Viviane Massonneau
  • Patent number: 5861302
    Abstract: 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: Grant
    Filed: June 10, 1994
    Date of Patent: January 19, 1999
    Assignee: The Research and Development Institute at Montana State University
    Inventors: Andrea Stierle, Donald Stierle, Gary Strobel
  • Patent number: 5861515
    Abstract: 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: Grant
    Filed: October 31, 1997
    Date of Patent: January 19, 1999
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: Alain Commercon, Eric Didier, Elie Fouque
  • Patent number: 5856532
    Abstract: 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: Grant
    Filed: August 12, 1997
    Date of Patent: January 5, 1999
    Assignee: Council of Scientific & Industrial Research
    Inventors: Sunil Kumar Chattopadhyay, Ram Prakash Sharma, Sushil Kumar, Kunnath Padmanabhan Madhusudanan
  • Patent number: 5854278
    Abstract: 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: Grant
    Filed: May 29, 1996
    Date of Patent: December 29, 1998
    Assignee: Xechem International, Inc.
    Inventors: Ramesh C. Pandey, Luben K. Yankov, Raghu Nair, Alex Poulev
  • Patent number: 5847170
    Abstract: 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: Grant
    Filed: March 26, 1996
    Date of Patent: December 8, 1998
    Assignee: Rhone-Poulenc Rorer, S.A.
    Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commer.cedilla.on
  • Patent number: 5840929
    Abstract: The present invention concerns novel paclitaxel derivatives, their use as antitumor agents, and pharmaceutical formulations.
    Type: Grant
    Filed: September 9, 1996
    Date of Patent: November 24, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventor: Shu-Hui Chen
  • Patent number: 5840748
    Abstract: 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: Grant
    Filed: December 13, 1995
    Date of Patent: November 24, 1998
    Assignee: Xechem International, Inc.
    Inventors: Luben K. Yankov, Ramesh C. Pandey
  • Patent number: 5840930
    Abstract: 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: Grant
    Filed: November 4, 1996
    Date of Patent: November 24, 1998
    Assignee: Xechem International, Inc.
    Inventors: Luben K. Yankov, Ramesh C. Pandey
  • Patent number: 5840931
    Abstract: 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: Grant
    Filed: April 24, 1997
    Date of Patent: November 24, 1998
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commer.cedilla.on, Corinne Terrier, Martine Zucco
  • Patent number: 5831102
    Abstract: 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: Grant
    Filed: February 8, 1996
    Date of Patent: November 3, 1998
  • Patent number: 5824701
    Abstract: 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: Grant
    Filed: February 3, 1997
    Date of Patent: October 20, 1998
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Annapurna Pendri
  • Patent number: 5821263
    Abstract: 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: Grant
    Filed: July 29, 1997
    Date of Patent: October 13, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventors: Paul M. Scola, Dolatrai M. Vyas
  • Patent number: 5821363
    Abstract: 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: Grant
    Filed: July 23, 1996
    Date of Patent: October 13, 1998
    Assignee: Pharmacia & Upjohn Company
    Inventors: Nancy A. Wicnienski, Robert C. Kelly, Peter G. M. Wuts
  • Patent number: 5814658
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: September 29, 1998
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commercon
  • Patent number: 5811452
    Abstract: 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: Grant
    Filed: January 8, 1997
    Date of Patent: September 22, 1998
    Assignees: The Research Foundation of State University of New York, Health Research Inc
    Inventors: Iwao Ojima, Ralph J. Bernacki
  • Patent number: 5807977
    Abstract: 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: Grant
    Filed: January 12, 1995
    Date of Patent: September 15, 1998
    Assignee: Aerojet General Corporation
    Inventors: Aslam A. Malik, Thomas G. Archibald
  • Patent number: 5808113
    Abstract: 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: Grant
    Filed: May 7, 1997
    Date of Patent: September 15, 1998
    Assignee: Hauser, Inc.
    Inventors: Christopher K. Murray, Qun Y. Zheng, Xiaoqin Cheng, S. Kent Peterson
  • Patent number: 5808102
    Abstract: 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: Grant
    Filed: August 22, 1997
    Date of Patent: September 15, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventors: Michael A. Poss, Jerome L. Moniot, Ivan D. Trifunovich, David J. Kucera, John K. Thottahil, Shu-Hui Chen, Jianmei Wei
  • Patent number: 5807888
    Abstract: 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: Grant
    Filed: May 29, 1996
    Date of Patent: September 15, 1998
    Assignee: Xechem International, Inc.
    Inventors: Ramesh C. Pandey, Luben K. Yankov, Raghu Nair, Alex Pouley
  • Patent number: 5801191
    Abstract: 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: Grant
    Filed: June 1, 1995
    Date of Patent: September 1, 1998
    Assignee: Biophysica Foundation
    Inventors: Jerome C. Bressi, James G. Douglass, III, Allen Seligson, Milos Sovak
  • Patent number: 5786489
    Abstract: 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: Grant
    Filed: April 1, 1996
    Date of Patent: July 28, 1998
    Assignee: The Scripps Research Institute
    Inventors: Kyriacos C. Nicolaou, Philippe G. Nantermet, Rodney K. Guy, Hiroaki Ueno
  • Patent number: 5777139
    Abstract: 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: Grant
    Filed: December 6, 1996
    Date of Patent: July 7, 1998
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: Herve Bouchard, Jean-Dominique Boureat, Alain Commer.cedilla.on
  • Patent number: 5773461
    Abstract: The present invention concerns novel paclitaxel derivatives, their use as antitumor agents, and pharmaceutical formulations.
    Type: Grant
    Filed: June 4, 1997
    Date of Patent: June 30, 1998
    Assignees: 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
  • Patent number: 5773464
    Abstract: The present invention concerns novel paclitaxel derivatives, their use as antitumor agents, and pharmaceutical formulations.
    Type: Grant
    Filed: August 29, 1997
    Date of Patent: June 30, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventors: Michael A. Walker, John F. Kadow
  • Patent number: 5770745
    Abstract: 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: Grant
    Filed: December 15, 1994
    Date of Patent: June 23, 1998
    Assignee: Bryn Mawr College
    Inventors: Charles S. Swindell, Nancy Krauss
  • Patent number: 5767282
    Abstract: A process of making taxane derivatives by reacting Baccatin III derivatives with an oxazolidine which contains a thioester substituent at the 4-position.
    Type: Grant
    Filed: February 20, 1997
    Date of Patent: June 16, 1998
    Assignee: Pharmacia & Upjohn S.p.A.
    Inventors: Cesare Gennari, Nicola Mongelli, Ermes Vanotti, Anna Vulpetti
  • Patent number: 5767296
    Abstract: 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: Grant
    Filed: December 6, 1996
    Date of Patent: June 16, 1998
    Assignee: Daiichi Pharmaceutical Co., Ltd.
    Inventors: Hirofumi Terasawa, Tsunehiko Soga, Kiyoshi Nakayama
  • Patent number: 5767297
    Abstract: 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: Grant
    Filed: June 3, 1997
    Date of Patent: June 16, 1998
    Assignees: Ensuiko Sugar Refining Co., Ltd., Tadakatsu MANDAI, Kaken Pharmaceutical Co., Ltd.
    Inventors: Tadakatsu Mandai, Hiroshi Okumoto, Koji Hara, Katsuhiko Mikuni, Kozo Hara, Hiroki Hamada