Daunomycin Or Derivative Patents (Class 536/6.4)
-
Publication number: 20100092388Abstract: Anthracycline derivatives are suitable for use in cancer therapy and diagnosis. These anthracycline derivatives can be radiolabelled and used as an imaging agent in cancer diagnosis. The radiolabelled anthracycline derivatives can also be used together with a drug delivery system, in particular including a two-step targeting strategy, for treating solid and disseminated tumours. These drug delivery system can advantageously be used for treatment and diagnosis of breast cancer.Type: ApplicationFiled: October 13, 2009Publication date: April 15, 2010Inventors: Katarina Edwards, Stefan Sjöberg, Jörgen Carlsson, Lars Gedda
-
Publication number: 20100075927Abstract: Chemotherapeutic conjugates of a peptide substrate to a phosphoramide chemotherapeutic agent in which a peptide substrate is covalently linked to the chemotherapeutic agent by a linker with an aminoarylmethyl or aminoheteroaryl moiety, wherein the linking of the peptide to the chemotherapeutic agent inhibits the cytotoxic activity of the chemotherapeutic agent, the peptide is a substrate for proteolytic cleavage by a tumor-specific enzyme; and the linker is capable of undergoing 1,6-elimination in vivo upon cleavage of the peptide substrate. Methods for synthesizing and methods of using the conjugates are also disclosed.Type: ApplicationFiled: November 29, 2007Publication date: March 25, 2010Applicant: Rutgers, The State University of New JerseyInventors: Longqin Hu, Xinghua Wu
-
Publication number: 20100069317Abstract: This invention relates to a novel crystalline polymorphic form of nemorubicin hydrochloride dihydrate, useful for the preparation of pharmaceutical composition for the treatment of tumors. A process for preparing this novel polymorphic form, named form A, is within the scope of the present invention.Type: ApplicationFiled: June 29, 2007Publication date: March 18, 2010Applicant: NERVIANO MEDICAL SCIENCES S.R.L.Inventors: Romualdo FORINO, Natale Alvaro BARBUGIAN, Attilio TOMASI, Giuseppina VISENTIN, Marco CATTANEO, Massimo ZAMPIERI
-
Publication number: 20100035799Abstract: The present invention relates to a method for the preparation of a compound of formula (I) or pharmaceutically acceptable salts thereof and intermediates thereof, comprising the steps of: a) halogenating a compound of formula (II), resulting in compound of formula (IIa), b) reacting a compound of formula (IIa) at its 14 position with the thiol moiety of a peptide of formula (III), optionally in the presence of a suitable linker, to obtain said compound of formula (I), wherein R1 represents OH, NH2 or NH-peptide; R2 represents H or —CO-peptide; R3 represents OCH3, OH or H; R4 represents H, or COCF3; R5 represents OH, O-tetrahydropyranyl or H; R6 represents OH or H; R7 represents H, OH, OCO(CH2)3CH3 or OCOCH(OC2H5)2; R8 represents OH or H; R9 represents OH or H; R10 represents a halogen and L is an optional suitable linker arm.Type: ApplicationFiled: September 30, 2009Publication date: February 11, 2010Applicants: Universite Catholique de Louvain, Diatos S. A.Inventors: Anne-Marie Fernandez, Vincent Dubois
-
Publication number: 20090325894Abstract: The present invention provides aminoside tetracyclic anthraquinones represented by formula (I) or formula (II), wherein the peptides are introduced to connect tetracyclic anthraquinones and fatty acid saturated or unsaturated in order to make the anticancer agents to be absorbed and released selectively; meanwhile some water-solubility groups are also introduced into the branched chain, aminosaccharide and tetracyclic moiety of the compounds to improve the water-solubility. The present invention also provides the preparative method and the use thereof as pharmaceutically active components for treating the diseases cured by aminoside tetracyclic anthraquinone, for example cancer, such as intestines, liver, gastric, breast, lung, ovary, prostate, brain glioma, lymph, skin, pigment, thyroid gland, multiple bone marrow cancer and leukemia.Type: ApplicationFiled: July 17, 2009Publication date: December 31, 2009Inventor: Hesheng Zhang
-
Publication number: 20090306004Abstract: A polymeric drug, in which a cancerostatic connected via spacers containing hydrolytically cleavable hydrazone bonds is bound to a water-soluble polymeric carrier prepared on the basis of a N-(2-hydroxypropyl)methacrylamide copolymer, wherein the structure of the polymeric drug consists of the main chain of N-(2-hydroxypropyl)methacrylamide carrying the cancerostatic and another chain of N-(2-hydroxypropyl)methacrylamide—a graft, which may also carry a cancerostatic, said grafts being bound to the main chain by a bond that is stable in the body and/or by a bond cleavable in the body, especially by an oligopeptide spacer selected from the series of GlyLeuGly, GlyPheGly, GlyPheLeuGly and GlyLeuPheGly, and a method of its preparation.Type: ApplicationFiled: September 18, 2007Publication date: December 10, 2009Inventors: Tomas Etrych, Petr Chytil, Karel Ulbrich, Thomas Mrkvan, Blanka Rihova
-
Publication number: 20090203889Abstract: Bivalent linkers derived from compounds of formulae (V), (VI), and (VII), where X1 and X2 are leaving groups and the other variables are as defined in the claims, to be included in or for preparing vitamin, drug, diagnostic agent, and/or imaging agent conjugates are described.Type: ApplicationFiled: July 22, 2005Publication date: August 13, 2009Applicant: ENDOCYTE, INC.Inventors: Iontcho Radoslavov Vlahov, Christopher Paul Leamon, Apparao Satyam, Stephen J. Howard
-
Patent number: 7560483Abstract: The present invention provides a method for synthesizing 1-(acyloxy)-alkyl derivatives from 1-acyl-alkyl derivatives, which typically proceeds stereospecifically, in high yield, does not require the use of activated intermediates and/or toxic compounds and is readily amendable to scale-up. The current invention also provides 1-acyl-alkyl derivatives of known drug components and methods for synthesizing these 1-acyl-alkyl derivatives.Type: GrantFiled: June 21, 2005Date of Patent: July 14, 2009Assignee: XenoPort, Inc.Inventors: Mark A. Gallop, Jia-Ning Xiang, Fenmei Yao, Laxminarayan Bhat, Cindy X. Zhou
-
Publication number: 20090176974Abstract: A method for the aralkylation of anthracyclins by utilizing an aralkylating agent R3-CH2X (for example, BnBr) in accordance with the reaction pathway describe by the scheme shown in FIG. 1. The present invention recognizes that 4-R1, 3?-N3-Daunomycines are suitable substrates for selective 4?-O-benzylation, yielding 4-R1, 3?-N3-4?-O-Aralkyl-Daunorubicines (in particular, 4?-O-Bn-Daunomycines). Thus, the present invention provides a pathway for a simple production of 4?-O-aralkylated derivatives of anthracyclines which can be effectively used to produce anthracyclines.Type: ApplicationFiled: May 23, 2008Publication date: July 9, 2009Inventors: Alexander F. Zabudkin, Victor Matvienko, Alexey Matveev, Aleksandr M. Itkin
-
Patent number: 7534766Abstract: A glucuronide metabolite of tigecycline, and its corresponding epimer, have been identified in humans treated with tigecycline. Mass spectral data have been used to identify these structures.Type: GrantFiled: November 2, 2005Date of Patent: May 19, 2009Assignee: WyethInventors: Ronald A. Jordan, William DeMaio, Matthew Hoffmann
-
Publication number: 20090118164Abstract: Bone targeted compounds and methods are provided. Compounds can include a Bone Targeting Portion (RT), having an affinity for bone; a Bone Active Portion (RA) for interacting with and affecting bone; and a Linking Portion (RL) connecting the Bone Targeting Portion and the Bone Active Portion.Type: ApplicationFiled: February 22, 2008Publication date: May 7, 2009Inventors: William M. Pierce, JR., K. Grant Taylor, Leonard C. Waite
-
Publication number: 20090099346Abstract: A crystalline form of epirubicin hydrochloride, named herein as “type II” crystalline epirubicin hydrochloride, has excellent thermal stability. Type II crystalline epirubicin hydrochloride has a powder X-ray diffraction pattern having average values of diffraction angle (2?) and relative intensity P(%) as presented in the following table: Diffraction Angle Relative Intensity 2? P % 5.2 100 9.2 24.5 10.3 14.3 13.7 32.8 14.6 10.9 15.5 49.3 18 19.1 19.2 21.1 19.4 11.3 20.7 19.9 21.1 29.7 21.4 18 22 23.1 22.5 69.6 23.6 20.5 24.1 72.1 25.8 67 26.1 15.9 27.7 47.9 29.8 38 31.9 14.1 32.1 16.7 36.4 16.6 37.7 18.8 41.1 14.Type: ApplicationFiled: October 5, 2008Publication date: April 16, 2009Inventors: Victor Matvienko, Alexey Matvyeyev, Aleksandr M. Itkin, Alexander F. Zabudkin
-
Patent number: 7485707Abstract: A crystalline form of epirubicin hydrochloride, named herein as “type II” crystalline epirubicin hydrochloride, has excellent thermal stability. Type II crystalline epirubicin hydrochloride has a powder X-ray diffraction pattern having average values of diffraction angle (2?) and relative intensity P(%) as presented in the following table: Diffraction Angle Relative Intensity 2? P (%) 5.236 9.8 9.212 12.5 13.732 15.5 16.446 4.8 18.234 5 21.114 9.7 22.529 25.5 24.071 29.9 25.879 18.4 27.762 16.5 29.757 10.1 34.392 4.4 38.157 13.1 44.293 5.9 64.699 7.7 77.815 100.Type: GrantFiled: June 25, 2004Date of Patent: February 3, 2009Assignee: Solux CorporationInventors: Victor Matvienko, Alexey Matvyeyev, Alexander F. Zabudkin, Aleksandr M. Itkin
-
Publication number: 20080293648Abstract: This invention provides methods, novel formulations and kits to reduce the toxicity of anticancer drugs. Disclosed are therapeutics and treatment methods employing anticancer drags that exhibit a known toxicity, including, for example, adriamycin, campthothecin, and the like, chemically linked to a phosphonoformic acid partial ester resulting in a novel formulation that significantly decreases drug-related toxicity, enhances synergy with other chemotherapeutic drugs and provides increased efficacy against drug-resistant cancers.Type: ApplicationFiled: December 19, 2007Publication date: November 27, 2008Applicant: Saha Pharmaceuticals, Inc.Inventor: Jayanta Saha
-
Patent number: 7445764Abstract: The invention relates to a carrier-drug conjugate comprising a carrier containing a polypeptide sequence having one or several cysteine radicals and a pharmacon containing a pharmaceutical and/or diagnostic active substance, a spacer molecule and a thiol binding group, whereby over 0.7 mol pharmacon per mol of cysteine radical is bound to the carrier by the thiol binding group. The invention also relates to a method for the production of said conjugate and to medicaments and diagnostic kits containing said conjugate.Type: GrantFiled: June 7, 2000Date of Patent: November 4, 2008Assignee: KTB Tumorforschungsgesellsschaft mbHInventor: Felix Kratz
-
Patent number: 7402556Abstract: The product of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide having a plasmin peptide substrate of 2-4 amino acids and mono- or di-peptide linkage, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by plasmin. Also disclosed are methods of making and using the prodrug compounds.Type: GrantFiled: August 23, 2001Date of Patent: July 22, 2008Assignee: Medarex, Inc.Inventors: André Trouet, Vincent Dubois, Alexandre Passioukov
-
Patent number: 7388083Abstract: A method of synthesizing R1, R2-substituted-4? (ax. or eq.)-OH anthracyclines and their corresponding salts of Formula (1) from daunorubicin or N-Trifluoroacetyl-4-R1-derivatives of daunorubicin, wherein R1 is defined as H, OH, and 4?-HO is defined as ax[ial]. The method includes producing N-Trifluoroacetyl daunorubicin and treating the N-Trifluoroacetyldaunorubicin or N-Trifluoroacetyl-4-R1-derivatives of daunorubicin, wherein R1 is defined as H, OH, with dimethylsulfoxide activated by different acylating agents. The attained intermediate product is then treated with a strong base (ex. tertiary amines) resulting in the 4?-keto-N-Trifluoroacetyl-4-R1 daunorubicin wherein R1 is defined as H, OH, OMe. The 4?-keto-N-Trifluoroacetyl-4-R1-daunorubicin is reacted with a reducing agent, a derivative of a borohydride of an alkaline metal MHBL3 , to produce N-Trifluoroacetyl-4?-epi-4-R1-daunorubicin.Type: GrantFiled: March 4, 2006Date of Patent: June 17, 2008Assignee: Solux CorporationInventors: Victor Matvienko, Alexey Matvyeyev, Alexander F. Zabudkin, Aleksandr M. Itkin
-
Publication number: 20080139490Abstract: Provided are polymorphic forms of valrubicin and processes for their preparation.Type: ApplicationFiled: September 25, 2007Publication date: June 12, 2008Inventors: Francesca Scarpitta, Csilla Nemethne Racz
-
Publication number: 20080132458Abstract: Prodrugs of cyclic anthracyclin toxins comprising a hypoxia-activated trigger and are disclosed. In addition, methods of treating cancer using the compounds of the invention are disclosed.Type: ApplicationFiled: March 10, 2005Publication date: June 5, 2008Applicant: Threshold Pharmaceuticals, Inc.Inventors: Mark Matteucci, Jian-Xin Duan
-
Publication number: 20080125380Abstract: The invention provides conjugates of fatty acids and anticancer agents useful in treating cancer, and compositions and formulations thereof. Methods for using the conjugates also are provided.Type: ApplicationFiled: June 21, 2007Publication date: May 29, 2008Applicant: Luitpold Pharmaceuticals, Inc.Inventors: Nigel L. Webb, Matthews O. Bradley, Forrest Anthony, Mark Fisher
-
Patent number: 7345023Abstract: The present invention relates to pharmaceutical formulations comprising an anthracycline and the uses thereof for treatment of clinical conditions of body surfaces such as skin and mucosal membranes, wherein abnormal cell differentiation and/or hyperproliferation is a primary factor of the pathogenesis. In particular the invention relates to treatment of psoriasis, and preferably to treatment of psoriasis with valrubicin topically applied.Type: GrantFiled: August 12, 2002Date of Patent: March 18, 2008Assignee: Valderm ApSInventors: Bjarne Bymose, Thomas Broe Christensen
-
Patent number: 7244829Abstract: 13-benzenesulfonylhydrazone anthracyclines useful in producing improved yields in the synthesis 13-deoxyanthrcyclines, and an improved method of reducing 13-benzene-sulfonylhydrazone anthracyclines to 13-deoxyanthrcyclines wherein the reduction reaction is maintained at temperatures of about 55° C. to 64° C. without stirring or agitation. The reaction is completed with the addition of aqueous bicarbonate which forms the 13-deoxyanthracycline and precipitates. The precipitates are filtered and the precipitate and filtrate are extracted separately with organic solvents. The crude 13-deoxy anthracycline can be converted to 5-imino-13-deoxy anthracycline by reaction with methanolic ammonia. The reaction can also be performed with an acidic pyridinium salt instead of a strong acid so that neutralization of the reaction or extraction of the product is not necessary, thereby facilitating purification.Type: GrantFiled: November 8, 2004Date of Patent: July 17, 2007Assignee: GEM Pharmaceuticals, LLCInventors: Gerald M. Walsh, Richard D. Olson
-
Patent number: 7153946Abstract: A molecular conjugate is provided having the formula: wherein R1 is a de-hydroxyl or de-amino moiety respectively of a hydroxyl-bearing or amino-bearing biologically active molecule or an analog or derivative thereof, and Z is —O— or —NH—, respectively, Y is a straight or branched alkyl having 1 to 20 carbons that may be optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl groups, electron-withdrawing groups, or electron-donating groups; and R2 is —CH?CH(W), —CH(OH)CH(OH)W, or —C(O)H, where W can be H, a straight or branched alkyl having 1 to 20 carbons that may be optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl groups, electron-withdrawing groups, or electron-donating groups.Type: GrantFiled: November 24, 2004Date of Patent: December 26, 2006Assignee: Tapestry Pharmaceuticals, Inc.Inventors: James D. McChesney, Madhavi C. Chander, Teruna J. Siahaan, Christine R. Xu, Sterling K. Ainsworth
-
Patent number: 7115576Abstract: The invention relates to novel pharmaceutical forms for antibiotics containing amino sugar, amphotericin B, daunorubicin and doxorubicin, in which the known side effects are reduced and which can be used in a simple manner. The antimycotic agent B is nephrotoxic. The cytostatic agents daunorubicin and doxorubicin are highly cardiotoxic. The novel pharmaceutical forms are antibiotic-starch conjugates, wherein the antibiotic is combined with the polysaccharide at the reducing end thereof by means of a peptide bond. According to the invention, said bond is carried out by means of J2 oxidation of the starch derivative at the reducing end thereof in an aqueous alkaline solution, and by coupling the starch derivative oxidised thereby to the antibiotic in an organic solution. The conjugates obtained are less toxic. The polysaccharide part can be decomposed by serum-?-amylase and the peptide bond can be accessed by an enzymatic attack.Type: GrantFiled: June 19, 2002Date of Patent: October 3, 2006Assignee: Fresenius Kabi Deutschland GmbHInventor: Klaus Sommermeyer
-
Patent number: 7109177Abstract: The present invention discloses new and novel substituted anthracyclines with modified alkyl-aromatic ring substitutions on the C-3? of the sugar moiety or modified or unmodified alkyl-aromatic ring substitutions at the C-4? of the sugar moiety. It also discloses novel methods for the preparation of sugar substrates and methods for the preparation of anthracycline antibiotics. These anthracycline analogs show high cytotoxicity in vitro against several tumor cell lines.Type: GrantFiled: January 6, 2004Date of Patent: September 19, 2006Assignee: Houston Pharmaceuticals, Inc.Inventors: Waldeman Priebe, Izabella Fokt, Teresa Przewloka, Marta Krawczyk, Piotr Skibicki, Grzegorz Grynkiewicz, Roman Perez-Soler
-
Patent number: 7091188Abstract: A stabilized amrubicin hydrochloride composition which comprises 3 to 8 wt. % water and 92 to 97 wt. % amrubicin hydrochloride; and a method of storing amrubicin hydrochloride.Type: GrantFiled: October 22, 2002Date of Patent: August 15, 2006Assignees: Sumitomo Chemical Company, Limited, Dainippon Sumitomo Pharma Co., Ltd.Inventors: Kazuhiko Takahashi, Koji Fujimoto, Yasuko Yamauchi, Takanori Okahashi
-
Patent number: 7053191Abstract: A method of synthesizing 4-R-substituted anthracyclines and their corresponding salts from 4-demethyldaunorubicin includes the steps of treating 4-demethyldaunorubicin with a sulfonylating agent to form 4-demethyl-4-sulfonyl-R3-daunorubicin. 4-Demethyl-4-R3-sulfonyl-daunorubicin is then subject to a reducing agent in the presence of a transition metal catalyst in a temperature range of about 30° C. to about 100° C. in a polar aprotic solvent in an inert atmosphere. Protected 4-demethoxy-4-R-daunomycin then undergoes hydrolysis in a basic solution to form the 4-R-substituted anthracyclines. The novel method lacks the step of forming a stereospecific glycoside bond between aglycone and aminoglycoside. The method also increases the yield of the final product up to 30 to 40%.Type: GrantFiled: April 23, 2004Date of Patent: May 30, 2006Assignee: Solux CorporationInventors: Alexander F. Zabudkin, Victor Matvienko, Alexey Matvyeyev, Aleksandr M. Itkin
-
Patent number: 7005421Abstract: According to the invention there is provided a sterile, pyrogen-free, ready-to-use solution of an anthracycline glycoside, especially doxorubicin, which consists essentially of a physiologically acceptable salt of an anthracycline glycoside dissolved in a physiologically acceptable solvent therefor, which has not been reconstituted from a lyophilizate and which has a pH of from 2.5 to 6.5. The solution of the invention is particularly advantageous for the administration by injection of the anthracycline glycoside drugs. e.g. doxorubicin, in the treatment of both human and animal tumors.Type: GrantFiled: June 4, 2003Date of Patent: February 28, 2006Assignee: Pharmacia & Upjohn CompanyInventors: Gaetano Gatti, Diego Oldani, Giuseppe Bottoni, Carlo Confalonieri, Luciano Gambini, Roberto De Ponti
-
Patent number: 7001991Abstract: A homogeneous conjugate for targeting and treating diseased cells wherein the conjugate comprises an anti-cancer drug and a targeting protein, wherein said anti-cancer drug is selected from the group consisting of heat sensitizers, photosensitizers and apoptosis inducing compounds, a method for making such a conjugate, and methods for using the conjugate. The targeting protein is preferably transferrin.Type: GrantFiled: May 15, 2002Date of Patent: February 21, 2006Assignee: Faulk Pharmaceuticals, Inc.Inventor: W. Page Faulk
-
Patent number: 6927211Abstract: Compositions and methods are provided for use in the treatment of cancer.Type: GrantFiled: December 4, 2003Date of Patent: August 9, 2005Assignee: Bristol-Myers Squibb CompanyInventors: Giorgio Minotti, Luca Gianni
-
Patent number: 6921841Abstract: It is described a process for the synthesis of optically active anthracyclines by the fact that the key intermediate (R)2-acetyl-2-hydroxy-1,2,3,4-tetrahydronaphtalene 5,8-dialkoxy-3,4-dihydronaphtalene by acylation asymmetric dihydroxylation, transformation into chloroacetate, dehydrochloridation and final hydrolysis.Type: GrantFiled: November 15, 2001Date of Patent: July 26, 2005Assignee: Menarini Richerche S.p.A.Inventors: Cristina Di Bugno, Fabio D'Arata, Alessio Ramacciotti, Paolo Crotti
-
Patent number: 6914046Abstract: Compounds inhibiting the activation of the nuclear factor ?B (NF-?B) are used for the preparation of medications adapted for the treatment of malignant hemopathies and solid tumors, and for the prevention of the appearance or the treatment, of phenomena of resistance to cytotoxic molecules used in the scope of treatment of the above pathologies, appearing in patients treated with these molecules when the latter are adapted to activate NF-?B.Type: GrantFiled: November 24, 1999Date of Patent: July 5, 2005Assignee: Centre National de la Recherche ScientifiqueInventors: Francois Hirsch, Astrid Haeffner
-
Patent number: 6906040Abstract: Compositions and methods are provided for use in the treatment of cancer.Type: GrantFiled: September 18, 2001Date of Patent: June 14, 2005Assignee: Bristol-Myers Squibb CompanyInventors: Giorgio Minotti, Luca Gianni
-
Patent number: 6844318Abstract: This invention is directed to antineoplastic agents conjugated to enzyme-cleavable peptides comprising the amino acid recognition sequence of a membrane-bound and/or cell-secreted peptidase, and to the use of such conjugated compounds as chemotherapeutic agents in the targeted treatment of cancers.Type: GrantFiled: March 15, 2001Date of Patent: January 18, 2005Assignee: Bristol Myers Squibb Pharma CompanyInventors: Robert A. Copeland, Charles F. Albright, Andrew P. Combs, Randine L. Dowling, Nilsa R. Graciani, Wei Han, C. Anne Higley, Pearl S. Huang, Eddy W. Yue, Susan V. DiMeo
-
Publication number: 20040249137Abstract: A stabilized amrubicin hydrochloride composition which comprises 3 to 8 wt. % water and 92 to 97 wt. % amrubicin hydrochloride; and a method of storing amrubicin hydrochloride.Type: ApplicationFiled: March 17, 2004Publication date: December 9, 2004Inventors: Kazuhiko Takahashi, Koji Fujimoto, Yasuko Yamauchi, Takanori Okahashi
-
Patent number: 6825166Abstract: A molecular conjugate is provided having the formula: wherein n is the conjugation number, P is a moiety of a carrier molecule such as a protein, R1 is a moiety of a biologically active molecule or its analogs, derivatives, salts or secondary amines, Z is —O— or —NH—, and Y is a straight or branched alkyl having 1 to 20 carbons optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl, electron-withdrawing or electron-donating groups. Compounds and methods useful in producing such molecular conjugates are also provided, as well as methods of concentrating biologically active molecules in selected target cells of a patient that comprise administering to the patient a selected dose of such molecular conjugates.Type: GrantFiled: March 25, 2002Date of Patent: November 30, 2004Assignee: Tapestry Pharmaceuticals, Inc.Inventors: James D. McChesney, Madhavi C. Chander, Teruna J. Siahaan, Christine R. Xu, Sterling K. Ainsworth
-
Publication number: 20040236086Abstract: A method of synthesizing 4-R-substituted anthracyclines and their corresponding salts from 4-demethyldaunorubicin includes the steps of treating 4-demethyldaunorubicin with a sulfonylating agent to form 4-demethyl-4-sulfonyl-R3-daunorubicin. 4-Demethyl-4-R3-sulfonyl-daunorubicin is then subject to a reducing agent in the presence of a transition metal catalyst in a temperature range of about 30° C. to about 100° C. in a polar aprotic solvent in an inert atmosphere. Protected 4-demethoxy-4-R-daunomycin then undergoes hydrolysis in a basic solution to form the 4-R-substituted anthracyclines. The novel method lacks the step of forming a stereospecific glycoside bond between aglycone and aminoglycoside. The method also increases the yield of the final product up to 30 to 40%.Type: ApplicationFiled: April 23, 2004Publication date: November 25, 2004Inventors: Alexander F. Zabudkin, Victor Matvienko, Alexey Matvyeyev, Aleksandr M. Itkin
-
Publication number: 20040214784Abstract: The present invention relates to the field of prodrugs of chemotherapeutic agents and method of use thereof.Type: ApplicationFiled: May 24, 2004Publication date: October 28, 2004Applicant: UNIVERSITY OF KENTUCKY RESEARCH FOUNDATIONInventors: Peter A. Crooks, Tadeusz Cynkowski, Grazyna Cynkowska, Hong Guo, Paul Ashton
-
Publication number: 20040209828Abstract: There are provided a method for making highly purified crystals of anthracycline derivatives, and a new crystalline form of 4-demethoxy-3′-deamino-3′-aziridinyl-4′-methansulfonyl daunorubicin, useful in the treatment of tumors.Type: ApplicationFiled: June 1, 2004Publication date: October 21, 2004Inventors: Alessandro Martini, Massimo Zampieri, Paolo Fumagalli, Ferdinando Giordano, Ruggero Bettini
-
Publication number: 20040180864Abstract: The present invention discloses novel aromatic azide derivatives and their bioconjugates for phototherapy of tumors and other lesions. The organic azides of the present invention are designed to absorb low-energy ultraviolet, visible, or near-infrared (NIR) region of the electromagnetic spectrum. The phototherapeutic effect is caused by direct interaction of nitrene, the reactive intermediate produced upon photoexcitation of the aromatic azide, with the tissue of interest. The compounds of the present invention are administered to a patient, allowed to accumulate at the site of the tumor or other lesion, and are exposed to light in order to perform a phototherapeutic procedure.Type: ApplicationFiled: March 24, 2004Publication date: September 16, 2004Applicant: MALLINCKRODT INC.Inventors: Raghavan Rajagopalan, Gary Cantrell, Samuel I. Achilefu, Joseph E. Bugai, Richard B. Dorshow
-
Publication number: 20040147463Abstract: Anthracycline glycosides of formula I, as reported in the description, wherein R is hydrogen, hydroxy or methoxy, R1 and R2, which are the same or different, are independently hydrogen or hydroxy, and the pharmaceutically acceptable salts thereof, are useful as anti-tumour agents.Type: ApplicationFiled: November 3, 2003Publication date: July 29, 2004Inventors: Alessandro Arcari, Mauro Gigli
-
Patent number: 6720306Abstract: A compound of Formula I, providing tetrapartate prodrugs is provided wherein: L1 is a bifunctional linking moiety; D is a moiety that is a leaving group, or a residue of a compound to be delivered into a cell; Z is covalently linked to [D]y, wherein Z is selected from the group consisting of: a moiety that is actively transported into a target cell, a hydrophobic moiety, and combinations thereof, Y1, Y2, Y3 and Y4 are each independently O, S, or NR12; R11 is a mono- or divalent polymer residue; R1, R4, R9, R10 and R12 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls and substituted C1-6 heteroalkyls; R2, R3, R5 and R6 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C1-6 alkoxy, phenoxy, C1-8 heteroalkyls, C1-8 heteroalkoxy, substituted C1-6 alkyls, C3-8 cycloalkyls, CType: GrantFiled: January 12, 2001Date of Patent: April 13, 2004Assignee: Enzon Pharmaceuticals, Inc.Inventors: Richard B. Greenwald, Hong Zhao
-
Patent number: 6716821Abstract: Cytotoxic agents bearing a polyethylene glycol (PEG) linking group having a terminal active ester, cytotoxic conjugates comprising one or more cytotoxic agents linked to a cell-binding agent via PEG linking groups, and methods for producing both are disclosed. A therapeutic composition comprising a therapeutically-effective amount of one of the cytotoxic conjugates of the present invention, and a method of killing selected cell populations comprising contacting target cells, or tissue containing target cells, with an effective amount of one of the cytotoxic conjugates, are also disclosed.Type: GrantFiled: December 21, 2001Date of Patent: April 6, 2004Assignee: Immunogen Inc.Inventors: Robert Yongxin Zhao, Michael Louis Miller, Wayne Charles Widdison, Ravi V. J. Chari
-
Patent number: 6709679Abstract: Conjugates of transferrin, albumin and polyethylence glycol consisting of native or thiolated transferrin or albumin or of polyethylene glycol (MW between approximately 5,000 and 20,0000) with at least one HS—, HO— or H2N group and cytostatic compounds derived through maleinimide or N-hydroxysuccinimide ester compounds, such as doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxandrone, chloroambucil, melphalan, 5-fluorouracyl, 5′-desoxy-5-fluorouridine, thioguanine, methotrexate, paclitaxel, docetaxel, topotecan, 9-aminocamptothecin, etoposide, teniposide, mitopodoside, vinblastine, vincristine, vindesine, vinorelbine or a compound of general formula A, B, C or D, where n=0-6, X=—NH2, —OH, —COOH, —O—CO—R—COR*, —NH—CO—R—COR*, where R is an aliphatic carbon chain with 1-6 carbon atoms or a substituted or unsubstituted phenylene group and R*H, phenyl, alkyl with 1-6 carbon atoms.Type: GrantFiled: August 20, 2001Date of Patent: March 23, 2004Inventor: Felix Kratz
-
Publication number: 20040044189Abstract: The present invention discloses a process for the semi-synthesis of 4-demethoxydaunomycinone, (8s-cis)-acetyl-10-hydroxy-7,8,9,10-tetrahydro-6,8,11-trihydroxy-5,12-naphthacenedione, of formula (I).Type: ApplicationFiled: December 19, 2002Publication date: March 4, 2004Inventors: Valentina Pizzamiglio, Walter Cabri, Elio Mapelli
-
Publication number: 20040029819Abstract: It is described a process for the synthesis of optically active anthracyclines characterised by the fact that the key intermediate (R)2-acetyl-2-hydroxy-1,2,3,4-tetrahydronaphtalene 5,8-dialkoxy is prepared from 5,8-dialcoxy-3,4-dihydronaphtalene by acylation asymmetric dihydroxylation, transformation into chloroacetate, dehydrochloridation and final hydrolysis.Type: ApplicationFiled: May 14, 2003Publication date: February 12, 2004Inventors: Cristina Di Bugno, Fabio D'Arata, Alessio Ramacciotti, Paolo Crotti
-
Patent number: 6680300Abstract: The present invention discloses new and novel substituted anthracyclines having a three ring system or other DNA binding moieties. These congeners show high activity in vitro against several tumor cell lines. The invention also describes anthracycline-based DNA alkylators.Type: GrantFiled: August 19, 2002Date of Patent: January 20, 2004Assignee: Board of Regents, The University of Texas SystemInventors: Waldemar Priebe, Teresa Przewloka, Izabela Fokt, Yi-He Ling, Roman Perez-Soler
-
Patent number: 6677309Abstract: Monomeric and dimeric anti-cancer drug aldehyde conjugate compounds and pharmaceutically acceptable salts thereof. Specifically, monomeric and dimeric aldehyde conjugates of 1-2, dihetero-substituted anti-cancer drugs, including monomeric and dimeric aldehyde conjugates of anthracyclines, are provided. Also provided are pro-drugs which, after administration, release monomeric aldehyde conjugates. Further provided are pharmaceutical and therapeutic compositions containing anti-cancer drug aldehyde conjugates and methods of treating cancer using the aldehyde conjugates.Type: GrantFiled: February 27, 1998Date of Patent: January 13, 2004Assignee: University Technology CorporationInventors: Dylan J. Taatjes, David J. Fenick, Tad H. Koch
-
Patent number: 6673907Abstract: The present invention discloses new and novel substituted anthracyclines with modified alkyl-aromatic ring substitutions on the C-3′ of the sugar moiety or modified or unmodified alkyl-aromatic ring substitutions at the C-4′ of the sugar moiety. It also discloses novel methods for the preparation of sugar substrates and methods for the preparation of anthracycline antibiotics. These anthracycline analogs show high cytotoxicity in vitro against several tumor cell lines.Type: GrantFiled: September 19, 2001Date of Patent: January 6, 2004Assignee: Houston Pharmaceuticals, Inc.Inventors: Waldemar Priebe, Izabella Fokt, Teresa Przewloka, Marta Krawczyk, Piotr Skibicki, Grzegorz Grynkiewicz, Roman Perez-Soler
-
Patent number: 6670348Abstract: Compounds having an ansamycin anitibiotic, or other moiety which binds to hsp90, coupled to a targeting moiety which binds specifically to a protein, receptor or marker can provide effective targeted delivery of the ansamycin antibiotic leading to the degradation of proteins and death of the targeted cells. These compositions may have different specificity than the ansamycin alone, allowing for a more specific targeting of the therapy, and can be effective in instances where the ansamycin alone has no effect. Thus, these compounds provide an entirely new class of targeted chemotherapy agents with application, depending on the nature of the targeting moiety, to treatment of a variety of different forms of cancer. Such agents can further be used to promote selective degradation of proteins associated with the pathogenesis of others diseases, including antigens associated with autoimmune disorders and pathogenic proteins associated with Alzheimer's disease.Type: GrantFiled: October 20, 1999Date of Patent: December 30, 2003Assignee: Sloan-Kettering Institute for Cancer ResearchInventors: Neal Rosen, Samuel Danishefsky, Ouathek Ouerfelli, Scott D. Kuduk, Laura Sepp-Lorenzino