WO1994011362A1 - Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them - Google Patents
Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them Download PDFInfo
- Publication number
- WO1994011362A1 WO1994011362A1 PCT/US1993/010473 US9310473W WO9411362A1 WO 1994011362 A1 WO1994011362 A1 WO 1994011362A1 US 9310473 W US9310473 W US 9310473W WO 9411362 A1 WO9411362 A1 WO 9411362A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hydrogen
- taxane derivative
- furyl
- carbons
- lower alkyl
- Prior art date
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- 0 C*C(*)C(*OC(C1)C(C)=C([C@](C(C(C)(C)[C@@]([C@]2*)C3(*)C(CCO)OC3)OC)O)C(C)(C)[C@@]12O)N Chemical compound C*C(*)C(*OC(C1)C(C)=C([C@](C(C(C)(C)[C@@]([C@]2*)C3(*)C(CCO)OC3)OC)O)C(C)(C)[C@@]12O)N 0.000 description 3
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/22—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/87—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/60—Ring systems containing bridged rings containing three rings containing at least one ring with less than six members
- C07C2603/62—Ring systems containing bridged rings containing three rings containing at least one ring with less than six members containing three- or four-membered rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- the present invention is directed to novel taxanes which have utility as antileukemia and antitumor agents.
- Taxol is a promising cancer chemotherapeutic agent with a broad spectrum of antileukemic and tumor-inhibiting activity. Taxol has a 2'R, 3'S configuration and the following structural formula:
- R' represents hydrogen or acetyl and one of R' ' and R' ' ' represents hydroxy and the other represents tert-butoxy- carbonylamino and their stereoisomeric forms, and mixtures thereof.
- the compound of formula (2) in which R' ' is hydroxy, R' ' ' is tert-butoxycarbonylamino having the 2'R, 3'S configuration is commonly referred to as taxotere.
- taxol and taxotere are promising chemotherapeutic agents, they are not universally effective. Accordingly, a need remains for additional chemotherapeutic agents.
- the present invention is directed to taxane derivatives of the formula:
- R x is phenyl or p-nitrophenyl-
- R 3 is furyl or thienyl
- T ⁇ is hydrogen, hydroxyl protecting group, or -COT 2 ,
- T 2 is H, Ci-C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocylic aryl, Ac is acetyl, and
- E 1 and E 2 are independently selected from hydrogen, hydroxy protecting groups and functional groups which increase the water solubility of the taxane derivative.
- Taxanes having formulas (4), (5) and (6) which have the 2'R, 3'S configuration may be obtained by reacting a ⁇ -lactam with metal alkoxides having the taxane tetracyclic nucleus and a C-13 metallic oxide substituent to form compounds having a ⁇ -amido ester substituent at C-13.
- the ⁇ -lactams have the following structural formula:
- R x is phenyl or p-nitrophenyl
- R 2 is a hydroxy protecting group
- R 3 is furyl or thienyl.
- ⁇ -lactams (7) can be prepared from readily available starting materials, as is illustrated by the following reaction scheme: OLi
- the 3-hydroxyl protecting group shown in the above reaction scheme is -SiR 5 wherein R 5 is trialkyl or triaryl such as triethyl.
- the 3-hydroxyl may be protected with other standard protecting groups such as 1-ethoxyethyl, or 2, 2,2-trichloroethoxymethyl . Additional hydroxy protecting groups and the synthesis thereof may be found in "Protective groups in Organic Synthesis" by T.W. Greene, John Wiley & Sons, 1981.
- racemic ⁇ -lactams may be resolved into the pure enantiomers prior to protection by recrystallization of the corresponding 2-methoxy-2- (trifluoromethyl) phenylacetic esters.
- the reaction described hereinbelow in which the ⁇ -amido ester side chain is attached has the advantage of being highly diastereo- selective, thus permitting the use of a racemic mixture of side chain precursor.
- the metal alkoxides having the taxane tetracyclic nucleus and a C-13 metallic oxide substituent have the following structural formula:
- T 1 is hydrogen, hydroxyl protecting group, or -C0T 2 ;
- T 2 is H, Ci-Cg alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocylic aryl;
- T 3 is hydrogen or a hydroxy protecting group;
- M is a metal, preferably selected from the group comprising Group IA, Group IIA and transition metals, most preferably, Li, Mg, Na, K or Ti.
- the metal alkoxides are prepared by reacting an alcohol having the taxane tetracyclic nucleus and a C-13 hydroxyl group with an organometallic compound in a suitable solvent.
- the alcohol is a protected baccatin III, in particular, 7-O-triethylsilyl baccatin III (which can be obtained as described by Greene, et al. in JACS 110: 5917 (1988) or by other routes) or 7,10-bis-O-triethylsilyl baccatin III.
- 10-deacetyl baccatin III is reacted with 20 equivalents of (C 2 H 5 ) 3 SiCl at 23°C under an argon atmosphere for 20 hours in the presence of 50 ml of pyridine/mmol of 10-deacetyl baccatin III to provide 7-triethylsilyl-'10-deacetyl baccatin III (10a) as a reaction product in 84-86% yield after purification.
- the reaction product may then optionally be acetylated with 5 equivalents of CH 3 C0C1 and 25 mL of pyridine/mmol of 10a at 0 OC under an argon atmosphere for 48 hours to provide 86% yield of 7-O-triethylsilyl baccatin III (10b) .
- the 7-O-triethylsilyl baccatin III (10b) is reacted with an organometallic compound such as n-butyllithium in a solvent such as tetrahydrofuran (THF) , to form the metal alkoxide 13-0-lithium-7-0-triethylsilyl baccatin III (11) as shown in the following reaction scheme:
- R is phenyl or p-nitrophenyl
- R 3 is phenyl
- Both the conversion of the alcohol to the metal alkoxide and the ultimate synthesis of the taxane derivative can take place in the same reaction vessel.
- the ⁇ -lactam is added to the reaction vessel after formation therein of the metal alkoxide.
- Compounds of formula (1) of the instant invention are useful for inhibiting tumor growth in animals including humans and are preferably administered in the form of a pharmaceutical composition comprising an effective antitumor amount of compound of the instant invention in combination with a pharmaceutically acceptable carrier or diluent.
- Antitumor compositions herein may be made up in any suitable form appropriate for desired use; e.g., oral, parenteral or topical administration.
- parenteral administration are intramuscular, intravenous, intraperitoneal, rectal and subcutaneous administration.
- the diluent or carrier ingredients should not be such as to diminish the therapeutic effects of the antitumor compounds.
- Suitable dosage forms for oral use include tablets, dispersible powders, granules, capsules, suspensions, syrups, and elixirs.
- Inert diluents and carriers for tablets include, for example, calcium carbonate, sodium carbonate, lactose- and talc.
- Tablets may also contain granulating and disintegrating agents such as starch and alginic acid, binding agents such as starch, gelatin and acacia, and lubricating agents such as magnesium stearate, stearic acid and talc. Tablets may be uncoated or may be coated by unknown techniques; e.g., to delay disintegration and absorption.
- Inert diluents and carriers which may be used in capsules include, for example, calcium carbonate, calcium phosphate and kaolin.
- Suspensions, syrups and elixirs may contain conventional excipients, for example, methyl cellulose, tragacanth, sodium alginate; wetting agents, such as lecithin and polyoxyethylene stearate; and preservatives, e.g., ethyl- p-hydroxybenzoate.
- Dosage forms suitable for parenteral administration include solutions, suspensions, dispersions, emulsions and the like. They may also be manufactured in the form of sterile solid compositions which can be dissolved or suspended in sterile injectable medium immediately before use. They may contain suspending or dispersing agents known in the art.
- the water solubility of compounds of formula (3) may be improved by modification of the C2' and/or C7 substituents to incorporate appropriate functional groups, E ⁇ and E 2 .
- Ej and E 2 may independently be hydrogen and -COGCOR 1 wherein
- R 2 hydrogen, methyl
- R 4 hydrogen, lower alkyl containing 1 to 4 carbons
- R 5 hydrogen, lower alkyl containing 1 to 4 carbons, benzyl, hydroxyethyl, CH 2 C0 2 H, dimethylaminoethyl
- R 7 lower alkyl containing 1 or 2 carbons, benzyl or R 6 and
- R 8 lower alkyl containing 1 or 2 carbons, benzyl
- the solution was warmed to 0 °C and kept at that temperature for 1 h before 1 mL of a 10% solution of AcOH in THF was added.
- the mixture was partitioned between saturated aqueous NaHC0 3 and 60/40 ethyl acetate/hexane.
- Taxanes 4, 5 and 6 was evaluated in .in vitro cytotoxicity activity against human colon carcinoma cells HCT-116 and HCT-116/VM46.
- the HCT116/VM cells are cells that have been selected for teniposide resistance and express the multidrug resistance phenotype, including resistance to taxol.
- Cytotoxicity was assessed in HCT116 and HCT VM46 human colon carcinoma cells by XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl) -5-[ (phenyl- a ino)carbonyl] -2H-t etrazolium hydroxide) assay (Scudiero et al, "Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines", Cancer Res. 48:4827-4833, 1988). Cells were plated at 4000 cells/well in 96 well microtiter plates and 24 hours later drugs were added and serial diluted.
- the cells were incubated at 37°c for 72 hours at which time the tetrazolium dye, XTT, was added.
- a dehydrogenase enzyme in live cells reduces the XTT to a form that absorbs light at 450 nm which can be quantitated spectrophotometrically.
- the results are expressed as an IC 50 which is the drug concentration required to inhibit cell proliferation (i.e. absorbance at 450 nm) to 50% of that of untreated control cells.
- the results are presented in Table 2. Lower numbers indicate greater activity.
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK94900474T DK0669918T3 (en) | 1992-11-13 | 1993-11-01 | Furyl or thienylcarbonyl-substituted taxanes and pharmaceutical compositions containing them |
DE69323436T DE69323436T2 (en) | 1992-11-13 | 1993-11-01 | FURYL OR THIENYLCARBONYL SUBSTITUTED TAXANS AND MEDICINAL PRODUCTS CONTAINING THEM |
JP51214994A JP3328286B2 (en) | 1992-11-13 | 1993-11-01 | Furyl or thienylcarbonyl-substituted taxanes and pharmaceutical compositions containing the same |
EP94900474A EP0669918B1 (en) | 1992-11-13 | 1993-11-01 | Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them |
AU55450/94A AU682161B2 (en) | 1992-11-13 | 1993-11-01 | Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them |
GR990401211T GR3030129T3 (en) | 1992-11-13 | 1999-04-30 | Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/975,723 US5283253A (en) | 1991-09-23 | 1992-11-13 | Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them |
US07/975,723 | 1992-11-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994011362A1 true WO1994011362A1 (en) | 1994-05-26 |
Family
ID=25523314
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1993/010473 WO1994011362A1 (en) | 1992-11-13 | 1993-11-01 | Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them |
Country Status (15)
Country | Link |
---|---|
US (1) | US5283253A (en) |
EP (1) | EP0669918B1 (en) |
JP (1) | JP3328286B2 (en) |
CN (1) | CN1051310C (en) |
AT (1) | ATE176466T1 (en) |
AU (1) | AU682161B2 (en) |
CA (1) | CA2147859A1 (en) |
DE (1) | DE69323436T2 (en) |
DK (1) | DK0669918T3 (en) |
ES (1) | ES2130390T3 (en) |
GR (1) | GR3030129T3 (en) |
IL (1) | IL107553A (en) |
MX (1) | MX9307052A (en) |
WO (1) | WO1994011362A1 (en) |
ZA (1) | ZA938214B (en) |
Families Citing this family (123)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5721268A (en) | 1991-09-23 | 1998-02-24 | Florida State University | C7 taxane derivatives and pharmaceutical compositions containing them |
US6018073A (en) * | 1991-09-23 | 2000-01-25 | Florida State University | Tricyclic taxanes having an alkoxy, alkenoxy or aryloxy substituted side-chain and pharmaceutical compositions containing them |
US6335362B1 (en) | 1991-09-23 | 2002-01-01 | Florida State University | Taxanes having an alkyl substituted side-chain and pharmaceutical compositions containing them |
US6011056A (en) | 1991-09-23 | 2000-01-04 | Florida State University | C9 taxane derivatives and pharmaceutical compositions containing them |
US6794523B2 (en) | 1991-09-23 | 2004-09-21 | Florida State University | Taxanes having t-butoxycarbonyl substituted side-chains and pharmaceutical compositions containing them |
US5728725A (en) * | 1991-09-23 | 1998-03-17 | Florida State University | C2 taxane derivaties and pharmaceutical compositions containing them |
US6495704B1 (en) | 1991-09-23 | 2002-12-17 | Florida State University | 9-desoxotaxanes and process for the preparation of 9-desoxotaxanes |
US5489601A (en) * | 1991-09-23 | 1996-02-06 | Florida State University | Taxanes having a pyridyl substituted side-chain and pharmaceutical compositions containing them |
US5728850A (en) * | 1991-09-23 | 1998-03-17 | Florida State University | Taxanes having a butenyl substituted side-chain and pharmaceutical compositions containing them |
US5739362A (en) * | 1991-09-23 | 1998-04-14 | Florida State University | Taxanes having an alkoxy, alkenoxy or aryloxy substituted side-chain and pharmaceutical compositions containing them |
US6028205A (en) * | 1991-09-23 | 2000-02-22 | Florida State University | C2 tricyclic taxanes |
US5478854A (en) * | 1992-10-01 | 1995-12-26 | Bristol-Myers Squibb Company | Deoxy taxols |
US5380751A (en) * | 1992-12-04 | 1995-01-10 | Bristol-Myers Squibb Company | 6,7-modified paclitaxels |
FR2698871B1 (en) | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | New taxoids, their preparation and the pharmaceutical compositions containing them. |
US5973160A (en) * | 1992-12-23 | 1999-10-26 | Poss; Michael A. | Methods for the preparation of novel sidechain-bearing taxanes |
US5646176A (en) | 1992-12-24 | 1997-07-08 | Bristol-Myers Squibb Company | Phosphonooxymethyl ethers of taxane derivatives |
US6710191B2 (en) * | 1993-03-05 | 2004-03-23 | Florida State University | 9β-hydroxytetracyclic taxanes |
ATE232854T1 (en) * | 1993-03-05 | 2003-03-15 | Univ Florida State | METHOD FOR PRODUCING 9-DESOXOTAXANES |
US5703247A (en) * | 1993-03-11 | 1997-12-30 | Virginia Tech Intellectual Properties, Inc. | 2-Debenzoyl-2-acyl taxol derivatives and methods for making same |
EP0690867B1 (en) * | 1993-03-22 | 2003-02-19 | Florida State University | Taxanes having furyl or thienyl substituted side-chain |
US5478860A (en) * | 1993-06-04 | 1995-12-26 | Inex Pharmaceuticals Corp. | Stable microemulsions for hydrophobic compound delivery |
CN100998565A (en) * | 1993-07-19 | 2007-07-18 | 血管技术药物公司 | Anti-angiogene compositions and methods of use |
US5677470A (en) | 1994-06-28 | 1997-10-14 | Tanabe Seiyaku Co., Ltd. | Baccatin derivatives and processes for preparing the same |
CA2162759A1 (en) * | 1994-11-17 | 1996-05-18 | Kenji Tsujihara | Baccatin derivatives and processes for preparing the same |
US5780653A (en) * | 1995-06-07 | 1998-07-14 | Vivorx Pharmaceuticals, Inc. | Nitrophenyl, 10-deacetylated substituted taxol derivatives as dual functional cytotoxic/radiosensitizers |
CA2178541C (en) * | 1995-06-07 | 2009-11-24 | Neal E. Fearnot | Implantable medical device |
CN1211919A (en) | 1995-09-13 | 1999-03-24 | 佛罗里达州立大学 | Radiosensitizing taxanes and their pharmaceutical preparations |
US5807888A (en) * | 1995-12-13 | 1998-09-15 | Xechem International, Inc. | Preparation of brominated paclitaxel analogues and their use as effective antitumor agents |
US5840748A (en) * | 1995-10-02 | 1998-11-24 | Xechem International, Inc. | Dihalocephalomannine and methods of use therefor |
US5654448A (en) * | 1995-10-02 | 1997-08-05 | Xechem International, Inc. | Isolation and purification of paclitaxel from organic matter containing paclitaxel, cephalomannine and other related taxanes |
US5854278A (en) * | 1995-12-13 | 1998-12-29 | Xechem International, Inc. | Preparation of chlorinated paclitaxel analogues and use thereof as antitumor agents |
US6177456B1 (en) | 1995-10-02 | 2001-01-23 | Xechem International, Inc. | Monohalocephalomannines having anticancer and antileukemic activity and method of preparation therefor |
IL126856A0 (en) | 1996-05-06 | 1999-09-22 | Univ Florida State | 1-Deoxy baccatin iii 1-deoxy taxol and 1-deoxy taxol analogs and method for the preparation thereof |
US5635531A (en) * | 1996-07-08 | 1997-06-03 | Bristol-Myers Squibb Company | 3'-aminocarbonyloxy paclitaxels |
US5811452A (en) * | 1997-01-08 | 1998-09-22 | The Research Foundation Of State University Of New York | Taxoid reversal agents for drug-resistance in cancer chemotherapy and pharmaceutical compositions thereof |
US6156789A (en) * | 1998-03-17 | 2000-12-05 | Rhone-Poulenc Rorer S.A. | Method for treating abnormal cell proliferation in the brain |
US6136988A (en) * | 1998-04-10 | 2000-10-24 | Hauser, Inc. | 7-hexanoyltaxol and methods for preparing the same |
US6333347B1 (en) * | 1999-01-29 | 2001-12-25 | Angiotech Pharmaceuticals & Advanced Research Tech | Intrapericardial delivery of anti-microtubule agents |
CA2385528C (en) | 1999-10-01 | 2013-12-10 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
US6649632B2 (en) * | 2000-02-02 | 2003-11-18 | Fsu Research Foundation, Inc. | C10 ester substituted taxanes |
SK13702001A3 (en) * | 2000-02-02 | 2002-06-04 | Florida State University Research Foundation, Inc. | C7 carbonate substituted taxanes as antitumor agent |
MXPA01009902A (en) | 2000-02-02 | 2003-07-28 | Univ Florida State Res Found | C10 carbonate substituted taxanes as antitumor agents. |
HUP0200651A3 (en) | 2000-02-02 | 2002-10-28 | Univ Florida State Res Found | C7 heterosubstituted acetate taxanes as antitumor agents and pharmaceutical compositions containing them |
AR030188A1 (en) * | 2000-02-02 | 2003-08-13 | Univ Florida State Res Found | TAXANO COMPOUNDS REPLACED WITH ESTERS IN C7; PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AND PROCESS TO TREAT A MAMMER SUBJECT THAT SUFFERS FROM A CONDITION THAT RESPONDS TO TAXANS |
JP2003521545A (en) * | 2000-02-02 | 2003-07-15 | フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド | Taxane formulation with improved solubility |
WO2001056564A1 (en) | 2000-02-02 | 2001-08-09 | Florida State University Research Foundation, Inc. | C10 heterosubstituted acetate taxanes as antitumor agents |
AU783422B2 (en) * | 2000-02-02 | 2005-10-27 | Florida State University Research Foundation, Inc. | C10 carbamoyloxy substituted taxanes as antitumor agents |
IL145643A0 (en) | 2000-02-02 | 2002-06-30 | Univ Florida State Res Found | C7 carbamoyloxy substituted taxanes as antitumor agents |
US6916942B2 (en) * | 2000-02-03 | 2005-07-12 | Bristol-Myers Squibb Company | Process for the preparation of C-4 carbonate taxanes |
US6750246B1 (en) | 2000-02-03 | 2004-06-15 | Bristol-Myers Squibb Company | C-4 carbonate taxanes |
US6362217B2 (en) | 2000-03-17 | 2002-03-26 | Bristol-Myers Squibb Company | Taxane anticancer agents |
CA2307393A1 (en) | 2000-05-01 | 2001-11-01 | The University Of British Columbia | Ginsenoside chemotherapy |
PL366100A1 (en) * | 2000-09-22 | 2005-01-24 | Bristol-Myers Squibb Company | Method for reducing toxicity of combined chemotherapies |
US20030157170A1 (en) * | 2001-03-13 | 2003-08-21 | Richard Liggins | Micellar drug delivery vehicles and precursors thereto and uses thereof |
WO2002072150A2 (en) * | 2001-03-13 | 2002-09-19 | Angiotech Pharmaceuticals Inc. | Micellar drug delivery vehicles and uses thereof |
NZ529647A (en) | 2001-04-20 | 2007-05-31 | Univ British Columbia | Micellar drug delivery systems for hydrophobic drugs |
US20030216758A1 (en) * | 2001-12-28 | 2003-11-20 | Angiotech Pharmaceuticals, Inc. | Coated surgical patches |
US20040210289A1 (en) * | 2002-03-04 | 2004-10-21 | Xingwu Wang | Novel nanomagnetic particles |
US7351542B2 (en) | 2002-05-20 | 2008-04-01 | The Regents Of The University Of California | Methods of modulating tubulin deacetylase activity |
JP2006516548A (en) | 2002-12-30 | 2006-07-06 | アンジオテック インターナショナル アクツィエン ゲゼルシャフト | Drug delivery from rapidly gelled polymer compositions |
US20040254419A1 (en) * | 2003-04-08 | 2004-12-16 | Xingwu Wang | Therapeutic assembly |
EP2390262A1 (en) | 2003-05-16 | 2011-11-30 | Intermune, Inc. | Synthetic chemokine receptor ligands and methods of use thereof |
US7064980B2 (en) * | 2003-09-17 | 2006-06-20 | Sandisk Corporation | Non-volatile memory and method with bit line coupled compensation |
US7407973B2 (en) * | 2003-10-24 | 2008-08-05 | Intermune, Inc. | Use of pirfenidone in therapeutic regimens |
US20070149496A1 (en) * | 2003-10-31 | 2007-06-28 | Jack Tuszynski | Water-soluble compound |
HN2005000054A (en) * | 2004-02-13 | 2009-02-18 | Florida State University Foundation Inc | REPLACED TAXANS WITH CYCLOPENTILO ESTERS IN C10 |
WO2005087222A1 (en) | 2004-03-05 | 2005-09-22 | Florida State University Research Foundation, Inc. | C7 lactyloxy-substituted taxanes |
US20050249667A1 (en) * | 2004-03-24 | 2005-11-10 | Tuszynski Jack A | Process for treating a biological organism |
US8003122B2 (en) * | 2004-03-31 | 2011-08-23 | Cordis Corporation | Device for local and/or regional delivery employing liquid formulations of therapeutic agents |
US7989490B2 (en) * | 2004-06-02 | 2011-08-02 | Cordis Corporation | Injectable formulations of taxanes for cad treatment |
US7846940B2 (en) * | 2004-03-31 | 2010-12-07 | Cordis Corporation | Solution formulations of sirolimus and its analogs for CAD treatment |
KR20070085227A (en) * | 2004-08-09 | 2007-08-27 | 앨리오스 바이오파마 인크. | Synthetic hyperglycosylated, protease-resistant polypeptide variants, oral formulations and methods of using the same |
US7597884B2 (en) * | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
PE20061090A1 (en) * | 2005-02-14 | 2006-10-12 | Univ Florida State Res Found | PREPARATIONS OF SUBSTITUTED TAXANS WITH CYCLOPROPYL ESTERS IN C10 |
US8691780B2 (en) * | 2005-02-17 | 2014-04-08 | The Board Of Trustees Of The Leland Stanford Junior University | Txr1 and enhanced taxane sensitivity based on the modulation of a pathway mediated thereby |
US20070073385A1 (en) * | 2005-09-20 | 2007-03-29 | Cook Incorporated | Eluting, implantable medical device |
US20070196423A1 (en) * | 2005-11-21 | 2007-08-23 | Med Institute, Inc. | Implantable medical device coatings with biodegradable elastomer and releasable therapeutic agent |
RU2448697C2 (en) | 2006-03-22 | 2012-04-27 | Медигене Аг | Treating three receptor negative breast cancer |
PL217731B1 (en) | 2006-06-01 | 2014-08-29 | Tomasz Byrski | Detection of lowered response for chemotherapy with the use of cytostatics from a group of toxoids |
ATE519511T1 (en) | 2006-06-30 | 2011-08-15 | Cook Inc | METHOD FOR PRODUCING AND MODIFYING TAXAN COATINGS FOR IMPLANTABLE MEDICAL DEVICES |
WO2008033466A2 (en) * | 2006-09-14 | 2008-03-20 | Combinatorx (Singapore) Pre. Ltd. | Compositions and methods for treatment of viral diseases |
US20080241215A1 (en) * | 2007-03-28 | 2008-10-02 | Robert Falotico | Local vascular delivery of probucol alone or in combination with sirolimus to treat restenosis, vulnerable plaque, aaa and stroke |
US8420110B2 (en) | 2008-03-31 | 2013-04-16 | Cordis Corporation | Drug coated expandable devices |
JP2011517455A (en) * | 2008-03-31 | 2011-06-09 | フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド | C (10) ethyl ester and C (10) cyclopropyl ester substituted taxanes |
US8409601B2 (en) | 2008-03-31 | 2013-04-02 | Cordis Corporation | Rapamycin coated expandable devices |
US8273404B2 (en) | 2008-05-19 | 2012-09-25 | Cordis Corporation | Extraction of solvents from drug containing polymer reservoirs |
CA2724550C (en) | 2008-05-22 | 2017-01-03 | Kereos, Inc. | Combination antitumor therapy |
EP2310507A4 (en) | 2008-07-08 | 2013-03-20 | David Gladstone Inst | Methods and compositions for modulating angiogenesis |
US8642063B2 (en) * | 2008-08-22 | 2014-02-04 | Cook Medical Technologies Llc | Implantable medical device coatings with biodegradable elastomer and releasable taxane agent |
WO2010028175A1 (en) | 2008-09-08 | 2010-03-11 | The Board Of Trustees Of The Leland Stanford Junior University | Modulators of aldehyde dehydrogenase activity and methods of use thereof |
US9198968B2 (en) | 2008-09-15 | 2015-12-01 | The Spectranetics Corporation | Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens |
WO2010062308A1 (en) | 2008-10-28 | 2010-06-03 | The Board Of Trustees Of The Leland Stanford Junior University | Modulators of aldehyde dehydrogenase and methods of use thereof |
US10457659B2 (en) | 2011-04-29 | 2019-10-29 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for increasing proliferation of adult salivary stem cells |
US20120302954A1 (en) | 2011-05-25 | 2012-11-29 | Zhao Jonathon Z | Expandable devices coated with a paclitaxel composition |
US20120303115A1 (en) | 2011-05-25 | 2012-11-29 | Dadino Ronald C | Expandable devices coated with a rapamycin composition |
US9956385B2 (en) | 2012-06-28 | 2018-05-01 | The Spectranetics Corporation | Post-processing of a medical device to control morphology and mechanical properties |
KR102165464B1 (en) | 2012-07-19 | 2020-10-14 | 레드우드 바이오사이언스 인코포레이티드 | Antibody specific for cd22 and methods of use thereof |
EP2916835A4 (en) | 2012-11-12 | 2016-07-27 | Redwood Bioscience Inc | Compounds and methods for producing a conjugate |
CN110423282B (en) | 2013-02-15 | 2023-09-08 | 加利福尼亚大学董事会 | Chimeric antigen receptor and methods of use thereof |
KR20150135332A (en) | 2013-03-14 | 2015-12-02 | 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 | Mitochondrial aldehyde dehydrogenase-2 modulators and methods of use thereof |
CA2927806C (en) | 2013-11-27 | 2023-01-10 | Redwood Bioscience, Inc. | Hydrazinyl-pyrrolo compounds and methods for producing a conjugate |
PL3107899T3 (en) | 2014-02-19 | 2021-01-25 | Aviv Therapeutics, Inc. | Mitochondrial aldehyde dehydrogenase 2 (aldh2) binding polycyclic amides and their use for the treatment of cancer |
KR20180058759A (en) | 2015-09-25 | 2018-06-01 | 제트와이 테라퓨틱스 인코포레이티드 | Pharmaceutical preparations based on microparticles comprising a polysaccharide-vitamin conjugate |
WO2017083637A1 (en) | 2015-11-12 | 2017-05-18 | The Board Of Trustees Of The Leland Stanford Junior University | Cell-penetrating, guanidinium-rich oligophosphotriesters for drug and probe delivery |
TWI760319B (en) | 2015-12-30 | 2022-04-11 | 杏國新藥股份有限公司 | Treatment of breast cancer |
CN109640961B (en) | 2016-06-01 | 2021-11-02 | 施维雅知识产权英国有限公司 | Polyalkylene oxide-asparaginase formulations and methods of making and using same |
CA3049674A1 (en) | 2017-01-18 | 2018-07-26 | F1 Oncology, Inc. | Chimeric antigen receptors against axl or ror2 and methods of use thereof |
EP3388082A1 (en) | 2017-04-13 | 2018-10-17 | Galera Labs, LLC | Combination cancer immunotherapy with pentaaza macrocyclic ring complex |
SG11202007317XA (en) | 2018-01-31 | 2020-08-28 | Galera Labs Llc | Combination cancer therapy with pentaaza macrocyclic ring complex and platinum-based anticancer agent |
JP2021521173A (en) | 2018-04-11 | 2021-08-26 | オハイオ・ステイト・イノベーション・ファウンデーション | Methods and compositions for sustained release microparticles for intraocular drug delivery |
EP3823674A4 (en) | 2018-07-18 | 2022-12-28 | Manzanita Pharmaceuticals, Inc. | Conjugates for delivering an anti-cancer agent to nerve cells, methods of use and methods of making thereof |
WO2020148612A1 (en) | 2019-01-14 | 2020-07-23 | Ignite Immunotherapy, Inc. | Recombinant vaccinia virus and methods of use thereof |
US11685904B2 (en) | 2019-02-14 | 2023-06-27 | Ignite Immunotherapy, Inc. | Recombinant vaccinia virus and methods of use thereof |
JP2022527860A (en) | 2019-04-02 | 2022-06-06 | ケンジョッケティ バイオテクノロジー,インク. | Emission Pump-Cancer Antigen Multispecific Antibodies and Their Related Compositions, Reagents, Kits and Methods |
KR20220113467A (en) | 2019-12-12 | 2022-08-12 | 이그나이트 이뮤노테라피, 인크. | Variant oncolytic vaccinia virus and methods of use thereof |
MX2022009355A (en) | 2020-01-29 | 2022-09-02 | Kenjockety Biotechnology Inc | Anti-mdr1 antibodies and uses thereof. |
AU2021284240A1 (en) | 2020-06-04 | 2022-12-08 | Kenjockety Biotechnology, Inc. | Anti-ABCG2 antibodies and uses thereof |
CN116529267A (en) | 2020-06-04 | 2023-08-01 | 肯乔克蒂生物技术股份有限公司 | ABCG2 efflux pump-cancer antigen multispecific antibodies and related compositions, reagents, kits and methods |
BR112023000650A2 (en) | 2020-07-14 | 2023-01-31 | Pfizer | RECOMBINANT VACCINIA VIRUS |
CA3193588A1 (en) | 2020-09-02 | 2022-03-10 | Kenjockety Biotechnology, Inc. | Anti-abcc1 antibodies and uses thereof |
EP4244257A1 (en) | 2020-11-13 | 2023-09-20 | Kenjockety Biotechnology, Inc. | Anti-mrp4 (encoded by abcc4 gene) antibodies and uses thereof |
WO2023114658A1 (en) | 2021-12-13 | 2023-06-22 | Kenjockety Biotechnology, Inc. | Anti-abcb1 antibodies |
WO2023159220A1 (en) | 2022-02-18 | 2023-08-24 | Kenjockety Biotechnology, Inc. | Anti-cd47 antibodies |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4942184A (en) * | 1988-03-07 | 1990-07-17 | The United States Of America As Represented By The Department Of Health And Human Services | Water soluble, antineoplastic derivatives of taxol |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1256444A (en) * | 1986-04-30 | 1989-06-27 | Kazunori Kan | Process for preparing 4-acetoxy-3- hydroxyethylazetidin-2-one derivatives |
FR2601676B1 (en) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | PROCESS FOR THE PREPARATION OF TAXOL AND DESACETYL-10 TAXOL |
FR2601675B1 (en) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | TAXOL DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
FR2629819B1 (en) * | 1988-04-06 | 1990-11-16 | Rhone Poulenc Sante | PROCESS FOR THE PREPARATION OF BACCATIN III AND DESACETYL-10 BACCATIN III DERIVATIVES |
FR2629818B1 (en) * | 1988-04-06 | 1990-11-16 | Centre Nat Rech Scient | PROCESS FOR THE PREPARATION OF TAXOL |
US4960790A (en) * | 1989-03-09 | 1990-10-02 | University Of Kansas | Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof |
US5175315A (en) * | 1989-05-31 | 1992-12-29 | Florida State University | Method for preparation of taxol using β-lactam |
US5136060A (en) * | 1989-11-14 | 1992-08-04 | Florida State University | Method for preparation of taxol using an oxazinone |
US5015744A (en) * | 1989-11-14 | 1991-05-14 | Florida State University | Method for preparation of taxol using an oxazinone |
US5059699A (en) * | 1990-08-28 | 1991-10-22 | Virginia Tech Intellectual Properties, Inc. | Water soluble derivatives of taxol |
MX9102128A (en) * | 1990-11-23 | 1992-07-08 | Rhone Poulenc Rorer Sa | DERIVATIVES OF TAXANE, PROCEDURE FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITION THAT CONTAINS THEM |
-
1992
- 1992-11-13 US US07/975,723 patent/US5283253A/en not_active Expired - Lifetime
-
1993
- 1993-11-01 DE DE69323436T patent/DE69323436T2/en not_active Expired - Fee Related
- 1993-11-01 JP JP51214994A patent/JP3328286B2/en not_active Expired - Fee Related
- 1993-11-01 WO PCT/US1993/010473 patent/WO1994011362A1/en active IP Right Grant
- 1993-11-01 EP EP94900474A patent/EP0669918B1/en not_active Expired - Lifetime
- 1993-11-01 AT AT94900474T patent/ATE176466T1/en not_active IP Right Cessation
- 1993-11-01 DK DK94900474T patent/DK0669918T3/en active
- 1993-11-01 ES ES94900474T patent/ES2130390T3/en not_active Expired - Lifetime
- 1993-11-01 CA CA002147859A patent/CA2147859A1/en not_active Abandoned
- 1993-11-01 AU AU55450/94A patent/AU682161B2/en not_active Ceased
- 1993-11-03 ZA ZA938214A patent/ZA938214B/en unknown
- 1993-11-10 IL IL107553A patent/IL107553A/en not_active IP Right Cessation
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- 1993-11-13 CN CN93114654A patent/CN1051310C/en not_active Expired - Fee Related
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1999
- 1999-04-30 GR GR990401211T patent/GR3030129T3/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4942184A (en) * | 1988-03-07 | 1990-07-17 | The United States Of America As Represented By The Department Of Health And Human Services | Water soluble, antineoplastic derivatives of taxol |
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US5283253A (en) | 1994-02-01 |
IL107553A (en) | 1997-11-20 |
ATE176466T1 (en) | 1999-02-15 |
AU5545094A (en) | 1994-06-08 |
IL107553A0 (en) | 1994-02-27 |
EP0669918A4 (en) | 1995-07-10 |
ES2130390T3 (en) | 1999-07-01 |
EP0669918B1 (en) | 1999-02-03 |
DE69323436T2 (en) | 1999-09-09 |
GR3030129T3 (en) | 1999-07-30 |
JPH08502995A (en) | 1996-04-02 |
CN1094401A (en) | 1994-11-02 |
DK0669918T3 (en) | 1999-09-20 |
JP3328286B2 (en) | 2002-09-24 |
ZA938214B (en) | 1994-07-19 |
CA2147859A1 (en) | 1994-05-26 |
CN1051310C (en) | 2000-04-12 |
AU682161B2 (en) | 1997-09-25 |
EP0669918A1 (en) | 1995-09-06 |
DE69323436D1 (en) | 1999-03-18 |
MX9307052A (en) | 1994-05-31 |
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