The Hetero Ring Is Four-membered Patents (Class 549/510)
  • Patent number: 6291690
    Abstract: This invention provides a taxane derivative of the formula: wherein a hydrophobic organic moiety is attached to a taxane. R and R1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R1 is not H. Attachment of a hydrophobic organic moiety to the taxane so as to obtain a taxane derivative generally stabilizes the association of the derivative with a lipid, including a liposomal lipid, carrier in the plasma of animals to which the derivative-carrier association is administered. Also provided herein is a composition containing the taxane derivative and a pharmaceutically acceptable medium; desirably, the medium also contains a lipid carrier, and the derivative is associated with the carrier. Further provided herein is a method of administering taxane derivatives to animals, for example, animals afflicted with cancers.
    Type: Grant
    Filed: May 9, 2000
    Date of Patent: September 18, 2001
    Assignee: The Liposome Company, Inc.
    Inventors: Eric Mayhew, J. Craig Franklin, Suresh Bhatia, Paul A. Harmon, Andrew S. Janoff
  • Patent number: 6291692
    Abstract: Process for the preparation of a derivative or analog of baccatin III or 10-desacetyl baccatin III having a C9 substituent other than keto in which the C9 keto substituent of taxol, a taxol analog, baccatin III or 10-desacetyl baccatin III is selectively reduced to the corresponding hydroxy group.
    Type: Grant
    Filed: October 12, 2000
    Date of Patent: September 18, 2001
    Assignee: Florida State University
    Inventors: Robert A. Holton, Carmen Somoza, Yukio Suzuki, Mitsuru Shindo
  • Publication number: 20010021783
    Abstract: New taxoids of general formula (I), their preparation, and pharmaceutical compounds containing them.
    Type: Application
    Filed: January 16, 2001
    Publication date: September 13, 2001
    Applicant: Rhne-Poulenc Rorer S.A.
    Inventors: Herv?eacute; Bouchard, Jean-Dominique Bourzat, Alain Commercon
  • Patent number: 6284898
    Abstract: Polymerizable and hydrolysable oxetane silanes and in particular silicic acid condensates which can be prepared therefrom are described, which exhibit only a low volume shrinkage on polymerization and produce polymers with high mechanical strength and therefore can be used above all as dental material or constituent thereof.
    Type: Grant
    Filed: June 9, 2000
    Date of Patent: September 4, 2001
    Assignee: Ivoclar AG
    Inventors: Norbert Moszner, Thomas Voelkel, Sabine Stein, Volker Rheinberger
  • Publication number: 20010018531
    Abstract: The invention relates to water soluble antitumor analogs of paclitaxel of formula (I) wherein R1═C(O)CH2CH(OH)COOX, R2═H, C(O)CH2CH(OH)COOX, X═H, Li, Naa or any other pharmaceutically acceptable counterion, as well as to a pharmaceutical composition comprising an antineoplastically effective amount of such analogs as an active ingredient.
    Type: Application
    Filed: February 21, 2001
    Publication date: August 30, 2001
    Inventors: Peter H.G. Wiegerinck, Duncan Sperling, Lesly Braamer, Eric W.P. Damen, Johan W. Scheeren, Dick de Vos
  • Patent number: 6281368
    Abstract: A process for producing 10-deacetyl baccatin III from an acidic solution containing a spectrum of taxanes, comprising contacting the acidic solution containing the spectrum of taxanes with a hydrazine hydrate, thereby to convert into 10-deacetyl baccatin III some taxanes in said solution that are not 10-deacetyl baccatin III.
    Type: Grant
    Filed: March 16, 2000
    Date of Patent: August 28, 2001
    Assignee: NaPro BioTherapeutics, Inc.
    Inventors: James D. McChesney, Madhavi C. Chander, Douglas L. Rodenburg
  • Publication number: 20010014746
    Abstract: A process for preparing N-acyl, N-sulfonyl and N-phosphoryl substituted isoserine esters in which a metal alkoxide is reacted with a &bgr;-lactam.
    Type: Application
    Filed: March 13, 2001
    Publication date: August 16, 2001
    Inventor: Robert A. Holton
  • Patent number: 6271384
    Abstract: Onium salts of taxo-diterpenoid-Cn,2-O-aza-arenes form water soluble self-assembling nanostructures above a critical aggregation concentration. The onium salt of aza-arene includes a delocalized charge which renders derivatized taxo-diterpenoids amphoteric, enhances their solubility in water, and promotes self-assembly of water soluble nanostructures, e.g., helical fibular structures and spherical micellular structures. These same onium salts of taxo-diterpenoid-Cn,2-O-aza-arenes are employed as water soluble prodrugs. For example, taxol-2′-methylpyridinium tosylate (MPT) is characterized by an elevated aqueous solubility, rapid activation by serum protein, good stability in most other aqueous solutions, formation of a protein:taxol intermediate and good retention within the circulatory system. The toxicity of the activated form is comparable or greater than underivatized taxol. Furthermore, taxol-2′-MPT can be synthesized by a simple one step reaction between taxol and 2-fluoro-1-MPT.
    Type: Grant
    Filed: April 13, 1998
    Date of Patent: August 7, 2001
    Assignee: The Scripps Research Institute
    Inventors: K. C. Nicolaou, Wolfgang Wrasidlo, Rodney K. Guy, Emmanuel Pitsinos
  • Patent number: 6268381
    Abstract: The present invention relates to taxane derivatives each represented by the following formula (1): [wherein, A1 represents a group (in which R1 represents H or a (substituted) alkyl group) or a group (in which R2 represents an amino group, a mono- or di-alkylamino group, a piperidino group, a pyrrolidino group or a morpholino group), X represents H, an alkoxycarbonyl group or a benzoyl group, Y represents H or a trialkylsilyl group, A2 represents a furyl group, an alkylfuryl group, an alkyl group or a fluorophenyl group, Ac represents an acetyl group, and Bz represents a benzoyl group] or salts thereof; and drugs containing the same as an active ingredient. These compounds have excellent water solubility and antitumor activity.
    Type: Grant
    Filed: June 19, 2000
    Date of Patent: July 31, 2001
    Assignee: Kabushiki Kaisha Yakult Honsha
    Inventors: Hideaki Shimizu, Atsuhiro Abe, Takanori Ogawa, Hiroshi Nagata, Seigo Sawada
  • Patent number: 6262107
    Abstract: Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble chelator, polyethylene glycol or polymer such as poly (1-glutamic acid) or poly (1-aspartic acid). Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis and for prediction of paclitaxel uptake by tumors and radiolabeled DTPA-paclitaxel tumor imaging. Other embodiments include the coating of implantable stents for prevention of restenosis.
    Type: Grant
    Filed: July 1, 1999
    Date of Patent: July 17, 2001
    Assignee: PG-TXL Company L.P.
    Inventors: Chun Li, Sidney Wallace, Dong-Fang Yu, David J. Yang
  • Patent number: 6262281
    Abstract: The present invention relates to chemical compounds that are useful in the production of taxanes. The chemical compounds according to the present invention have a generalized formula: wherein R1 is NH2, and wherein R2 may be acetyl or hydrogen, and p1 may be hydrogen or a hydroxyl protecting group.
    Type: Grant
    Filed: February 9, 1998
    Date of Patent: July 17, 2001
    Assignee: Bryn Mawr College
    Inventors: Charles S. Swindell, Nancy Krauss
  • Patent number: 6255484
    Abstract: A cyanurate compound having three oxetane ring groups and represented by the general formula (1): wherein R1 represents a member selected from the group consisting of a hydrogen atom and alkyl groups having 1 to 6 carbon atoms, is useful as a photosetting monomer or thermosetting monomer, and thus is used, together with a hardening agent, for example, a polycarboxylic anhydride and a catalyst, for example, an amine, a carboxylic acid metal salt or a protonic acid, to provide an organic hardening composition usable for producing electronic materials, for example, resists.
    Type: Grant
    Filed: September 27, 2000
    Date of Patent: July 3, 2001
    Assignee: Ube Industries, Ltd.
    Inventors: Mikito Kashima, Yumiki Noda, Harutoshi Hoshino, Toshikazu Machida
  • Patent number: 6252094
    Abstract: Cyclic chemical switching method is employed for solubilizing and desolubilizing taxo-diterpenoids with respect to aqueous solvents. 2-Halogenated onium salts of aza-arenes are employed to derivatize taxo-diterpenoids so as to alter their solubility in aqueous solvents. The onium salt of aza-arene includes a delocalized charge which imparts polarity and aqueous solubility to taxo-diterpenoid derivatives. Solubilization is achieved in a one step derivatization with the onium salt of 2-halogenated aza-arenes. Desolubilization is achieved by contacting onium salts of taxo-diterpenoid-Cn,2-O-aza-arenes with serum protein to displace the 2-O-aza-arene and form a soluble protein:taxo-diterpenoid intermediate. This protein:taxo-diterpenoid intermediate then dissociates over time to provide a bioactive taxo-diterpenoid. These same onium salts of taxo-diterpenoid-Cn,2-O-aza-arenes are employed as water soluble prodrugs. The toxicity of the activated form is comparable or greater than underivatized taxol.
    Type: Grant
    Filed: February 4, 1999
    Date of Patent: June 26, 2001
    Assignee: The Scripps Research Institute
    Inventors: K. C. Nicolaou, Wolfgang Wrasidlo, Rodney K. Guy, Emmanuel Pitsinos
  • Patent number: 6248908
    Abstract: A process for the synthesis of a C-4 methyl carbonate paclitaxel analog from 10-deacetylbaccatin III by the selective reduction of the acetate at the C-4 position of 10-deacetylbaccatin using Red-Al.
    Type: Grant
    Filed: August 10, 2000
    Date of Patent: June 19, 2001
    Assignee: Bristol-Myers Squibb Company
    Inventor: Joydeep Kant
  • Patent number: 6248572
    Abstract: The present invention provides a method for mass production of taxol which comprises adding sugar into a culture medium containing sugar in the course of semicontinuous culture of Taxus genus plant cell, and a universal method for mass production of taxol which comprises culturing Taxus genus plant cell in a culture medium containing sugar and AgNO3 as well. In accordance with the present invention, large amount of taxol can be produced with a high yield, simply by manipulating the culture condition of Taxus genus plant cell culture.
    Type: Grant
    Filed: December 22, 1998
    Date of Patent: June 19, 2001
    Assignee: Samyang, Genex, Corporation
    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, Ho-Joon Choi
  • Patent number: 6242614
    Abstract: A process for the synthesis of paclitaxel from 10-deacetylbaccatin-III which is protected at the 7-position with a dialkylalkoxysilyl protecting group having the formula —Si(R)2(OR′).
    Type: Grant
    Filed: May 25, 2000
    Date of Patent: June 5, 2001
    Assignee: Bristol-Myers Squibb Company
    Inventors: Purushotham Vemishetti, Francis S. Gibson, John L. Dillon
  • Publication number: 20010002423
    Abstract: Oxetane compounds represented by general formula (1), which are excellent in radical polymerizability and cationic polymerizability and in compatibility and copolymerizability with other copolymerizable monomers; a process for producing the compounds; and an oxetane copolymer which is excellent in compatibility among the monomer units and has a low water absorption and excellent transparency.
    Type: Application
    Filed: January 9, 2001
    Publication date: May 31, 2001
    Inventors: Naoki Sugiyama, Manabu Sekiguchi, Hozumi Sato
  • Patent number: 6232477
    Abstract: Methods of preparing new taxoids of general formula (I) are presented: in which: R4 represents an alkanoyloxy radical in which the alkanoyl portion contains 2 to 6 carbon atoms in an unbranched or branched chain, this radical unsubstituted or substituted with one or more halogen atoms, an alkoxy radical containing 1 to 4 carbon atoms, or alternatively R4 represents a cycloalkanoyloxy radical in which the cycloalkanoyl portion contains 4 to 8 carbon atoms, or alternatively R4 represents a benzoyloxy radical; R5 represents an alkoxy radical containing 1 to 4 carbon atoms, substituted by an alkylthio radical containing 1 to 4 carbon atoms; and Z represents a hydrogen atom or a radical of general formula:
    Type: Grant
    Filed: March 17, 2000
    Date of Patent: May 15, 2001
    Assignee: Aventis Pharma S.A.
    Inventors: Hervé Bouchard, Jean-Dominique Bourzat, Alain Commerçon
  • Patent number: 6229027
    Abstract: A process for obtaining paclitaxel and other taxanes from a source containing taxanes. The process involves extracting taxane compounds from the source into an organic solvent and passing this composition through a distribution chromatography column and eluting taxane compounds with the dry distribution column. The eluted taxane compounds are isolated by further processing techniques.
    Type: Grant
    Filed: March 10, 2000
    Date of Patent: May 8, 2001
    Inventor: Jian Liu
  • Patent number: 6225463
    Abstract: The object of the present invention is the development of new chiral auxiliaries for improved &bgr;-lactam formation that control both the diastereoselectivity of &bgr;-lactam formation and which can be removed without destruction of the sensitive azetidinone ring, providing valuable intermediates for coupling to the C-13 hydroxyl group of anti-tumor taxanes, such as paclitaxel. Further, the object of the present invention is enantiomerically pure (S)-(−)-1-(p-methoxy-phenyl)propyl-1-amine.
    Type: Grant
    Filed: December 15, 1998
    Date of Patent: May 1, 2001
    Assignees: Pharmachemie B.V., Cancer Research Campaign Technology Ltd.
    Inventors: Dick de Vos, Stephen Brown, Allan M. Jordan, Nicholas J. Lawrence, Alan Th. McGown
  • Patent number: 6222053
    Abstract: The present invention relates to a semi-synthetic process to convert a naturally occurring taxane into a suitable starting material for the synthesis of paclitaxel and related compounds. Specifically, the present invention relates to a process for the conversion of 9-dihydro-13-acetylbaccatin III into a 7-protected baccatin III which can then be used as starting material for the synthesis of taxane derivatives such as paclitaxel, docetaxel, cephalomannine and other taxanes structurally related to baccatin III. The method as described uses a preparative scale technique which is amenable to commercial scale-up.
    Type: Grant
    Filed: October 17, 1997
    Date of Patent: April 24, 2001
    Assignee: Institut National de la Recherche Scientifique
    Inventors: Lolita Zamir, Gaétan Caron
  • Patent number: 6218553
    Abstract: Taxol (I) is a complex deterpene which is currently considered the most exciting lead in cancer chemotherapy. Taxol possesses high cytotoxicity and strong antitumor activity against different cancers which have not been effectively treated by existing antitumor drugs. However, taxol has a problem with solubility in aqueous media, which may impose some serious limitation in its use. Taxotére (III) seems to have antitumor activity superior to taxol with better bioavailability. Taxotére has a modified taxol structure with a modified C-13 side chain. This fact strongly indicates that modification on the C-13 side chain would provide a new series of taxol and Taxotére analogues which may have higher potency, better bioavailability and less unwanted toxicity. The present invention provides efficient and practical methods for the syntheses of Taxotére and its analogues through &bgr;-lactam intermediates and their coupling with baccatin III.
    Type: Grant
    Filed: February 29, 2000
    Date of Patent: April 17, 2001
    Assignee: The State University of New York at Stony Brook
    Inventor: Iwao Ojima
  • Patent number: 6215000
    Abstract: Disclosed are crystalline complexes of baccatin III with imidazole, 2-methylimidazole or isopropanol, which are useful for isolating baccatin III from plant tissue cell culture and plant extracts containing baccatin Ill.
    Type: Grant
    Filed: March 28, 2000
    Date of Patent: April 10, 2001
    Assignee: Bristol-Myers Squibb Company
    Inventors: Francis S. Gibson, Jianmei Wei, John L. Dillon, Jr., Purushotham Vemishetti
  • Patent number: 6211363
    Abstract: The present invention relates to a novel taxol derivative having an antitumor-activity which is represented by formula (1). [In the formula (I), R1: a phenyl group, R2: an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an alkoxyl group, R3: a hydrogen atom, a hydroxyl group, a halogen atom, an alkoxyl group, a group —O—R31, an acyloxy group or a group —O—CO—R31, (in which R31: an alkylamino group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group), R4 and R5: a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic group, Z1: a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group, Z2: a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group, Z3: an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group].
    Type: Grant
    Filed: February 25, 2000
    Date of Patent: April 3, 2001
    Assignee: Daiichi Pharamaceutical Co., Ltd.
    Inventors: Hirofumi Terasawa, Tsunehiko Soga, Takashi Ishiyama
  • Patent number: 6201140
    Abstract: The present invention concerns novel 7-ethers of taxane derivatives, their use as antitumor agents and pharmaceutical compositions containing the novel compounds.
    Type: Grant
    Filed: July 28, 1994
    Date of Patent: March 13, 2001
    Assignee: Bristol-Myers Squibb Company
    Inventors: Henry Wong, Mark D. Wittman
  • Patent number: 6197981
    Abstract: Process for preparing taxol, baccatin III and 10-deacetylbaccatin III by oxidation of 9-dihydro-13-acetylbaccatin III.
    Type: Grant
    Filed: November 1, 1999
    Date of Patent: March 6, 2001
    Inventor: Jian Liu
  • Patent number: 6197980
    Abstract: 4-acetoxy-2&agr;-benzoyloxy-5&bgr;, 20-epoxy-1&bgr;, 7&bgr;, 10&bgr;-trihydroxy-9-oxo-11-taxen-13&agr;-y1(2R,3S)-3-t-butoxycarbonylamino-3-phenyl-2-hydroxypropionate trihydrate obtained by a process of centrifugal partition chromatography.
    Type: Grant
    Filed: August 20, 1999
    Date of Patent: March 6, 2001
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: André Durand, Alain Gerbaud, Rodolphe Margraff
  • Patent number: 6191287
    Abstract: Processes for the preparation of taxol and other taxanes through selective derivatization of the C(7) and C(10) hydroxyl groups of 10-DAB, particularly a novel process using a new strategy in which the C(10) hydroxyl group is protected or derivatized prior to the C(7) hydroxyl group; and the provision of C(7) and C(10) derivatized 10-DAB compounds.
    Type: Grant
    Filed: June 17, 1999
    Date of Patent: February 20, 2001
    Assignee: Florida State University
    Inventors: Robert A. Holton, Zhuming Zhang, Paul A. Clarke
  • Patent number: 6191290
    Abstract: The present invention describes for the first time the design and synthesis of a soluble tumor-directed paclitaxel prodrug which may establish a new mode of utilization of the taxane class of anticancer agents in cancer therapy.
    Type: Grant
    Filed: February 23, 2000
    Date of Patent: February 20, 2001
    Assignee: UAB Research Foundation
    Inventor: Ahmad Safavy
  • Patent number: 6187916
    Abstract: A process for the preparation of a taxane derivative of the formula in which R2 represents an RO—, RS— or RR′N— in which R represents an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl, or cycloalkyl, saturated heterocyclic, cycloalkenyl, unsaturated heterocyclic, aryl or heterocyclic aromatic; R′ is a hydrogen or R defined above; R and R′ can be connected to form together with the nitrogen a cyclic structure; Y is oxygen or sulfur; R3 represents an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, cycloalkenyl or an unsubstituted or substituted aryl; which comprises reacting a &bgr;-lactam of the formula in which R311 represents a radical R3 defined above or a protected R3 whenever R3 includes one or more active hydrogens; with a baccatin III derivative of the formula: in which M is an alkali metal
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: February 13, 2001
    Assignee: Research Foundation of State University of New York
    Inventor: Iwao Ojima
  • Patent number: 6184395
    Abstract: Novel reaction conditions for the cleavage of silyl ethers from silyl protected taxane precursors to afford paclitaxel and paclitaxel analogues in high yield and quality are described. Paclitaxel is prepared from a taxane precursor by treating the taxane precursor with a strong acid such as trifluoroacetic acid in a solvent such as aqueous acetic acid, such that the amount and number of side reactions and taxane impurities are significantly minimized. Also desribed are the crystallization methods for the isolation of paclitaxel in either of the two crystal forms A or B. Paclitaxel and paclitaxel analogues are anti-cancer agents.
    Type: Grant
    Filed: May 16, 2000
    Date of Patent: February 6, 2001
    Assignee: Bristol-Myers Squibb Company
    Inventors: Ambarish K. Singh, Raymond E. Weaver, Gerald L. Powers, Victor W. Rosso
  • Patent number: 6180802
    Abstract: New processes for the selective protection of the 7-position of 7,10-dihydroxytaxane derivatives, using &bgr;-substituted-alkoxycarbonyl groups which are more hindered than 2,2,2-trichloroethoxycarbonyl, and which are capable of being removed by a &bgr;-elimination mechanism, and the new intermediates resulting from these processes. The new intermediates of the invention are useful for preparing taxol and analogs thereof.
    Type: Grant
    Filed: May 19, 1998
    Date of Patent: January 30, 2001
    Assignee: Societe d'Etude et de Recherche en Ingenierie Pharmaceutique Seripharm
    Inventors: Luc Chanteloup, Bruno Chauveau, Christine Corbin, Robert Dhal, Sonia Le Guen, Arnaud Lamy, Antoine Leze, Jean-Pierre Robin
  • Patent number: 6177456
    Abstract: The present invention provides a 3″-monohalocephalomannine of the formula: wherein R is halogen.
    Type: Grant
    Filed: July 10, 1998
    Date of Patent: January 23, 2001
    Assignee: Xechem International, Inc.
    Inventors: Luben K. Yankov, Ramesh C. Pandey
  • Patent number: 6175022
    Abstract: Nucelophilic group, such as alcohol, terminated 2-oxetanone multimers, process of making same by reacting e.g. alcohol and dicarboxylic acid chloride in the presence of triethylamine, and their use for sizing paper.
    Type: Grant
    Filed: December 30, 1998
    Date of Patent: January 16, 2001
    Assignee: Hercules Incorporated
    Inventors: Clement L. Brungardt, Richard J. Riehle, Ian Vallance, Jian Jian Zhang
  • Patent number: 6175023
    Abstract: Compounds of the formula of are disclosed as well as a method of preparation.
    Type: Grant
    Filed: January 31, 2000
    Date of Patent: January 16, 2001
    Inventor: Jian Liu
  • Patent number: 6166228
    Abstract: A process is described for the production of 3-alkyl-3-hydroxymethyloxetanes of the general formula (1), ##STR1## in which R.sup.1 denotes a linear or branched C.sub.1 -C.sub.12 alkyl group, which process comprises reacting a trimethylolalkane of the general formula (2),(HO--CH.sub.2).sub.3 C--R.sup.1 (2)in which R.sup.1 is defined as above, with a dialkyl carbonate of the general formula (3),R.sup.2 --O--(C.dbd.O)--O--R.sup.2 (3)in which R.sup.2 denotes a linear or branched C.sub.1 -C.sub.4 alkyl group, in the presence of a basic catalyst, wherein in a first stage the reaction mixture is stirred for at least 6 hours with refluxing at a temperature of 90-120.degree. C., in a second stage the alcohol formed R.sub.2 OH is distilled off at the same temperature and in a third stage the product formed is decarboxylated and deoligomerised at a temperature of 125-150.degree. C. and the desired 3-alkyl-3-hydroxymethyloxetane is simultaneously distilled off.
    Type: Grant
    Filed: March 17, 2000
    Date of Patent: December 26, 2000
    Assignee: Dainippon Ink and Chemicals, Inc.
    Inventors: Kai-Uwe Gaudl, Artur Lachowicz, Andreas Hoffmann, Gerwald Grahe
  • Patent number: 6160135
    Abstract: Novel taxoids of general formula (I), the preparation thereof and pharmaceutical compositions containing same, are disclosed. In general formula (I), Z is a hydrogen atom or a radical of general formula (H), wherein R.sub.1 is an optionally substituted benzoyl radical or a radical R.sub.2 --O--CO--, where R.sub.2 is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, optionally substituted phenyl or heterocyclyl radical; R.sub.3 is an alkyl, alkenyl, alkyl, cycloalkyl, phenyl, naphthyl or aromatic heterocyclic radical; R.sub.4 is a hydroxy radical or an alkoxy, alkenyloxy, optionally substituted alkynyloxy, alkanoyloxy, alkenoyloxy, alkynyloxy, alkoxyacetyl or alkyloxycarbonyloxy radical, or a cycloalkyloxy, cycloalkenyloxy, arylcarbonyloxy or heterocyclylcarbonyloxy radical; and R.sub.5 is an optionally substituted alkoxy radical or a cycloalkyloxy or cycloalkenyloxy radical.
    Type: Grant
    Filed: August 4, 1998
    Date of Patent: December 12, 2000
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: Herve Bouchard, Jean-Dominique Bourzat, Alain Commer.cedilla.on
  • Patent number: 6153756
    Abstract: Novel 2'-onium salts of paclitaxel act as prodrugs in mammalian patients to yield paclitaxel in vivo. Methods of synthesizing these onium salts are disclosed, as are methods of treating patients suffering from paclitaxel-responsive diseases by administering effective amounts of the onium salts and pharmaceutical compositions containing the novel salts which are suitable for administration to patients requiring paclitaxel therapy.
    Type: Grant
    Filed: June 3, 1997
    Date of Patent: November 28, 2000
    Inventors: George A. Digenis, Kenneth H. Kortright
  • Patent number: 6150541
    Abstract: The present invention is directed to 4,10.beta.-diacetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1-hydroxy-9-oxo- 19-norcyclopropa(g)tax-11-en-13.alpha.-yl (2r,3s)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate dihydrate and a process for its preparation.
    Type: Grant
    Filed: June 10, 1998
    Date of Patent: November 21, 2000
    Assignee: Aventis Pharma S.A.
    Inventors: Eric Didier, Michel Lavigne, Jean-Rene Authelin
  • Patent number: 6150398
    Abstract: A pharmaceutical composition comprising an effective cancerous cell growth inhibiting amount of paclitaxel, or a paclitaxel derivative, and an effective cancerous cell growth inhibiting amount of an active agent which inhibits cancerous cell growth by exerting an effect on mammalian cell cycle during G.sub.1 or S-phase of the cell division cycle to inhibit said cancerous cell growth and methods of using same.
    Type: Grant
    Filed: March 20, 1996
    Date of Patent: November 21, 2000
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: George F. Vande Woude, Nicholas Schulz, Renping Zhou, Ira Daar, Marianne Oskarsson
  • Patent number: 6150537
    Abstract: The invention relates to a method for preparing an ester, by admixing a compound having the structure I or IV: ##STR1## with a base and an alcohol to produce an ester, wherein the alcohol is a precursor to Taxol and its analogs. The present invention also relates to compounds having the structure I and IV and methods of making them therefor. The invention also relates to the esterification of an alcohol by adding an alkoxide to a compound having the structure VII: ##STR2## The invention further relates to compounds having the structure I, IV, and VII and methods of making them therefor. The invention further relates to alcohols, and in particular, alcohols that are synthetic precursors to Taxol and analogs thereof.
    Type: Grant
    Filed: December 12, 1997
    Date of Patent: November 21, 2000
    Assignee: Emory University
    Inventors: Dennis C. Liotta, Hariharan Venkatesan, Laura Captain, Michael V. Voronkov, James P. Snyder, Marcus A. Schestopol
  • Patent number: 6147234
    Abstract: Taxane derivatives having alternative C9 substituents.
    Type: Grant
    Filed: July 16, 1999
    Date of Patent: November 14, 2000
    Assignee: Florida State University
    Inventors: Robert A. Holton, Carmen Somoza, Yukio Suzuki, Mitsuru Shindo
  • Patent number: 6140273
    Abstract: 2-Benzoylcyclohexane-1,3-diones of the formula I: ##STR1## where: R.sup.1 and R.sup.2 are each hydrogen, mercapto, nitro, halogen, cyano, thiocyanato, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -haloalkyl, C.sub.1 -C.sub.6 -alkoxy, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, --OR.sup.10, --OCOR.sup.10, --OSO.sub.2 R.sup.10, --S(O).sub.n R.sup.10, --SO.sub.2 OR.sup.10, --SO.sub.2 NR.sup.3 R.sup.10, --NR.sup.10 SO.sub.2 R.sup.10 or --NR.sup.10 COR;Q is a cyclohexane-1,3-dione ring with or without substitution, which is attached in position 2;A is a group of the formula IIa, IIb or III: ##STR2## where the substituents are as defined in claim 1, and agriculturally useful salts thereof are described.
    Type: Grant
    Filed: November 2, 1999
    Date of Patent: October 31, 2000
    Assignee: BASF Aktiengesellschaft
    Inventors: Stefan Engel, Ernst Baumann, Wolfgang von Deyn, Regina Luise Hill, Uwe Kardorff, Guido Mayer, Martina Otten, Joachim Rheinheimer, Oliver Wagner, Matthias Witschel, Ulf Misslitz, Helmut Walter, Karl-Otto Westphalen
  • Patent number: 6140494
    Abstract: Novel squarate dyes are described, and adducts of these dyes with biologically significant chemical species such as nucleosides or nucleotides. The adducts have useful properties for fluorescent nucleic acid sequencing methods.
    Type: Grant
    Filed: May 12, 1999
    Date of Patent: October 31, 2000
    Assignee: Amersham Pharmacia Biotech UK Limited
    Inventors: Alan Lewis Hamilton, Richard Martin West, William Jonathan Cummins, Mark Samuel Jonathan Briggs, Ian Edward Bruce
  • Patent number: 6136999
    Abstract: A chemical compound having the formula: ##STR1## wherein P.sub.1 is a hydroxyl protecting group, R.sub.1 may be H or electron withdrawing group, R.sub.2 may be H or electron withdrawing group, R.sub.3 may be H or electron withdrawing group, R.sub.4 may be H or electron withdrawing group, R.sub.5 may be H or electron withdrawing group, R.sub.6 may be an alkyl group, an olefinic group, an aromatic group, Ph, PhCH.sub.2, an O-alkyl group, an O-olefinic group, an O-aromatic group, O--Ph, or O--CH.sub.2 Ph.
    Type: Grant
    Filed: June 21, 1999
    Date of Patent: October 24, 2000
    Assignee: NaPro BioTherapeutics, Inc.
    Inventors: Madhavi C. Chander, James D. McChesney, Jan Zygmunt
  • Patent number: 6136988
    Abstract: An antitumor compound of formula (5) ##STR1## and also provided by the present invention is a method of preparing a compound of formula (5) whereby diesterification of the alcohol groups located at the 2' and 7 positions of paclitaxel is followed by the hydrolysis of the 2' hexanoate group resulting in 7-hexanoyltaxol.
    Type: Grant
    Filed: April 10, 1998
    Date of Patent: October 24, 2000
    Assignee: Hauser, Inc.
    Inventors: Christopher K. Murray, Qun Y. Zheng, Sagar R. Shakya
  • Patent number: 6136989
    Abstract: A method of isolating paclitaxel from pactitaxel-containing material that includes the steps of obtaining an acetone mixture of the paclitaxel-containing material, then mixing the acetone mixture with an aqueous solvent to form an aqueous supernatant and a precipitate, wherein the precipitate contains at least 3-times higher paclitaxel content than the paclitaxel extract. The acetone/water precipitation step provides a high yield of highly pure paclitaxel that is suitable for industrial scale isolation using conventional normal-phase silica chromatography steps, and the preparation of pharmaceutical compositions containing paclitaxel.
    Type: Grant
    Filed: December 30, 1998
    Date of Patent: October 24, 2000
    Assignee: Phytogen Life Sciences, Incorporated
    Inventors: Samuel Siang Kiang Foo, Yili Bai, Martin Ehlert
  • Patent number: 6136990
    Abstract: A taxoid compound represented by general formula (I) ##STR1## where the symbols R.sup.1, R.sup.2, R.sup.3, R.sup.4, Bz, and Ac have specified meanings. Also, a method for producing the taxoid derivative from a baccatin derivative having a .beta.-ketoester group at the 13-position by transesterification and a method for producing taxoid compound such as paclitaxel from the taxoid derivative under mild condition are disclosed.
    Type: Grant
    Filed: February 15, 2000
    Date of Patent: October 24, 2000
    Assignees: Bio Research Corporation of Yokohama, Ensuiko Sugar Refining Co., Ltd., Tadakatsu Mandai
    Inventors: Tadakatsu Mandai, Hiroshi Okumoto, Katsuyoshi Nakanishi, Koji Hara, Katsuhiko Mikuni, Kozo Hara
  • Patent number: 6136961
    Abstract: Highly specific biocatalytic reactions have been used to create a population of derivatives from a single starting compound. Examples demonstrate synthesis of derivatives of taxol, taxol-2'-adipate, taxol-2'-vinyl adipate, 2,3-(methylenedioxy) benzaldehyde, (.+-.)-(2-endo, 3-exo)-bicyclo (2.2.2)octo-5-ene-2,3-dimethanol, adenosine and erythromycin.
    Type: Grant
    Filed: June 29, 1998
    Date of Patent: October 24, 2000
    Assignee: EnzyMed, Inc.
    Inventors: Jonathan S. Dordick, Douglas S. Clark, Peter C. Michels, Yuri L. Khmelnitsky
  • Patent number: 6133462
    Abstract: A compound for use in the production of taxanes and intermediates therefor having the formula: ##STR1## wherein R is an alkyl group.
    Type: Grant
    Filed: September 2, 1997
    Date of Patent: October 17, 2000
    Assignees: NaPro BioTherapeutics, Inc., Bryn Mawr College
    Inventors: Nicholas J. Sisti, Charles S. Swindell