Three Or More Ring Hetero Atoms In The Pentacyclo Ring System Patents (Class 546/48)
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Patent number: 6552197Abstract: Disclosed are a process for the preparation of a compound represented by the formula (1), which comprises treating a compound represented by the formula (2) with methanesulfonic acid and then subjecting the thus-treated compound to recrystallization; and Compound (1) so obtained. This Compound (1) is free of hygroscopicity, excellent in filterability and solubility and easy in handling. Furthermore, according to the preparation process of the present invention, an unnecessary isomer can be converted into the target one and separation of the target isomer can be conducted easily.Type: GrantFiled: June 11, 2001Date of Patent: April 22, 2003Assignees: Daiichi Pharmaceutical Co., Ltd., Kabushiki Kaisha Yakult HonshaInventors: Shinji Kamihara, Kazuaki Kanai, Shigeru Noguchi, Hirofumi Terasawa, Hiroaki Kitaoka
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Publication number: 20030073698Abstract: (20S) esters of camptothecin analogs are provided. The compounds are (20S) esters of an aminoalkanoic acid or an imidoalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.Type: ApplicationFiled: May 23, 2002Publication date: April 17, 2003Inventors: Li-Xi Yang, Xiandao Pan, Huijuan Wang
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Publication number: 20030032624Abstract: (20S) esters of camptothecin analogs are provided. The compounds are (20S) esters of an aminoalkanoic acid or an imidoalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.Type: ApplicationFiled: June 14, 2002Publication date: February 13, 2003Inventor: Li-Xi Yang
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Patent number: 6512118Abstract: A camptothecin derivative comprising a compound of the formula [I] is disclosed: wherein R1, R2, R3, R4 and R5 are (A) adjacent two groups combine to form alkylene, or both are H, and one of the remaining three groups is —Xn-Alkm-R6, and the other two are H, alkyl or halogen, or (B) adjacent two groups combine to form alkylene, and one of the carbon atoms of said alkylene group is substituted by —Xn-Alkm-R6, and the remaining three groups are H, alkyl or a halogen, and one or two —CH2— of the alkylene in (A) or (B) may optionally be replaced by —O—, —S— or —NH—, X is —O— or —NH—, Alk is alkylene, R6 is —NH2, or —OH, m and n are both 0 or 1, or m is 1 and n is 0, which camptothecin compound is bound to a polysaccharide having carboxyl groups via an amino acid or a peptide, or a pharmaceutically acceptable salt thereof.Type: GrantFiled: January 8, 1999Date of Patent: January 28, 2003Assignee: Tanabe Seiyaku Co., Ltd.Inventors: Kenji Tsujihara, Takayuki Kawaguchi, Satoshi Okuno, Toshiro Yano
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Patent number: 6509344Abstract: A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity versus topoisomerase I. The two most cytotoxic indenoisoquinolines proved to be cis-6-ethyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8,9(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline and cis-6-allyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8,9-(methylenedioxy)-5,11-dioxo-(11H)indeno[1,2-c]isoquinoline. Two of the most potent topoisomerase I inhibitors were 6-(3-carboxy-1-propyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (26) and 6-ethyl-2,3-dimethoxy-8,9-(methylenedioxy)-11H-indeno[1,2-c]isoquinolinium chloride (27).Type: GrantFiled: July 20, 2001Date of Patent: January 21, 2003Assignees: The United States of America as represented by the Department of Health and Human Services, Office of Technology Transfer National Institute of HealthInventors: Mark S. Cushman, Pamela M. Nagafuji, Muthusamy Jayaraman, Yves G. Pommier
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Patent number: 6506734Abstract: The present invention relates to glycoconjugates of 20(S)-camptothecin, in which a 3-O-methylated &bgr;-L-fucose unit is linked to the 20-hydroxyl group of a camptothecin derivative via a thiourea-modified peptide spacer. The invention furthermore relates to processes for the preparation of the compounds according to the invention and to their use as medicaments, in particular in connection with oncoses.Type: GrantFiled: October 27, 1999Date of Patent: January 14, 2003Assignee: Bayer AktiengesellschaftInventors: Hans-Georg Lerchen, Karsten von dem Bruch, Jörg Baumgarten, Michael Sperzel
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Patent number: 6500953Abstract: The invention concerns the preparation of nothapodytine or camptothecin derivatives which consists in causing 4-ethyl 2methyl hepta-2,4-dienoic acid act on a 3-aminomethyl 2-bromo quinoline derivative (III) wherein R1 and R2 are H or R1 is a halogen atom or alkyl, R2 is a O—CO—X radical as defined for the camptothecin derivatives; or R1 and R2 are defined for the known camptothecin derivatives or represent protected radicals or radicals easily convertible into the radicals R1 and R2, to obtain the quinoline derivative (IV); adding to the resulting quinoline derivative (2-methoxy carbonyl vinyl) tributyltin in the presence of a complex of palladium and triphenylarsin to obtain the quinoline derivative (V); cyclizing the resulting quinoline derivative to obtain the tetracyclic derivative (VI); then in subjecting said derivative to an ozonolysis followed by treatment with dimethyl sulphide to obtain the tetracyclic derivative (VII); saponification followed by decarboxylation in oxidising conditions oType: GrantFiled: January 26, 2001Date of Patent: December 31, 2002Assignee: Aventis Pharma S.A.Inventors: Khalid Mekouar, Yves Genisson, Stefanie Leue, Andrew-Elliot Greene
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Patent number: 6492335Abstract: The present invention relates to glycoconjugates of camptothecin derivatives in which at least one carbohydrate component is linked via suitable spacers with the 20-hydroxyl group of a camptothecin derivative. The invention furthermore relates to processes for preparing the compounds according to the invention and to their use as medicaments, in particular in connection with cancer.Type: GrantFiled: March 24, 1999Date of Patent: December 10, 2002Assignee: Bayer AktiengesellschaftInventors: Hans-Georg Lerchen, Karsten von dem Bruch, Jörg Buamgarten, Michael Sperzel
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Patent number: 6492379Abstract: A polymorphic form of 9-nitrocamptothecin is provided, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 175.5 and 177.5° C., an exotherm at between 181.7 and 183.7° C., and an IR spectrum with no absorption centered between 3625 cm−1 and 3675 cm−1.Type: GrantFiled: February 21, 2002Date of Patent: December 10, 2002Assignee: Super Gen, Inc.Inventors: Sanjeev Redkar, Ashok Gore
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Patent number: 6486320Abstract: The present invention relates to a novel process for preparation of camptothecin and of its derivatives by convergent synthesis starting from a 3-(aminomethyl)quinoline derivative and 5-hydroxy-5-ethyl-6-oxo-5,6-dihydropyrancarboxylic acid and to the intermediates obtained.Type: GrantFiled: September 14, 2001Date of Patent: November 26, 2002Assignee: Aventis Pharma S.A.Inventors: Stefanie Leue, Stéphanie Garçon, Andrew-Elliot Greene, Yves Génisson, Patrick Léon
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Patent number: 6486167Abstract: The present invention provides compounds of formula I: wherein the R substituents and atoms X and Y are as defined in specification. The present invention also provides pharmaceutical compositions and methods of inhibiting cancer cell growth.Type: GrantFiled: September 29, 2000Date of Patent: November 26, 2002Assignee: Rutgers, The State University of New JerseyInventors: Edmond J. La Voie, Darshan B. Makhey, Baoping Zhao, Leroy Fong Liu
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Patent number: 6482830Abstract: A polymorphic form of 9-nitrocamptothecin is provided, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 149.2 and 151.2° C., an exotherm at between 162.6 and 164.6° C., and an exotherm at between 272 and 274° C.Type: GrantFiled: February 21, 2002Date of Patent: November 19, 2002Assignee: SuperGen, Inc.Inventors: Sanjeev Redkar, Ashok Gore
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Patent number: 6476225Abstract: A process for purifying 20(S)-camptothecin, the process comprising: (a) combining an aqueous base and a starting material containing 20(S)-camptothecin to convert the lactone ring of the 20(S)-camptothecin into a carboxylate salt; (b) hydrogenating to the product of step (a) in the presence of a transition metal catalyst; (c) acidifying the aqueous phase of the product of step (b) to form 20(S)-camptothecin crystals; (d) adding at least one polar aprotic solvent to the product of step (c); and (e) separating off the purified 20(S)-camptothecin crystals.Type: GrantFiled: January 17, 2002Date of Patent: November 5, 2002Assignee: Boehringer Ingelheim Pharma KGInventors: Rainer Sobotta, Armin Rapp
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Publication number: 20020160994Abstract: A process for the preparation of a compound of the formula 1Type: ApplicationFiled: January 30, 2002Publication date: October 31, 2002Applicant: SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES (S.C.R.A.S.)Inventors: Dennis Bigg, Olivier Lavergne, Francesc Pla Rodas, Jacques Pommier, Gerard Ulibarri, Jerry Harnett, Alain Rolland, Anne-Marie Liberatore, Christophe Lanco, Jean-Bernard Cazaux, Christine Le Breton, Eric Manginot
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Publication number: 20020147341Abstract: The present invention is directed to novel fused pyrrolocarbazoles and isoindolones, including pharmaceutical compositions, diagnostic kits, assay standards or reagents containing the same, and methods of using the same as therapeutics. The invention is also directed to intermediates and processes for making these novel compounds.Type: ApplicationFiled: February 1, 2002Publication date: October 10, 2002Applicant: Cephalon, Inc.Inventor: Robert L. Hudkins
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Publication number: 20020128281Abstract: Compounds of formula (I), wherein X is selected from the group consisting of O, and NR3, where R3 represents a lower alkyl group; Y is selected from the group consisting of CH and N; R1 and R2 are independently selected from the group consisting of NH2, NHR4 and NR52, where R4 and R5 each represent a lower alkyl group, or R1 and R2 together represent a cycle selected from (a), (b) and (c), wherein R6, R7 and R8 are independently selected from the group consisting of hydrogen atoms, lower alkyl groups, hydroxy groups and lower alkoxy groups; and Z is selected from the group consisting of O.Type: ApplicationFiled: September 24, 2001Publication date: September 12, 2002Applicant: Universidad Complutense de madridInventors: Jose Luis Fernandez Puentes, Dolores Garcia Gravalos, Carmen Avendano Lopez, Maria del Mar Blanco Castro, Jose Carlos Menendez Ramos
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Patent number: 6444820Abstract: This invention discloses and claims novel intermediates and procedures for the synthesis of camptothecin derivatives, such as irinotecan, and other compounds related to the synthesis of CPT-11. Related procedures and compounds are also disclosed, such as a novel method of making mappicine.Type: GrantFiled: October 13, 2000Date of Patent: September 3, 2002Inventors: Kevin E. Henegar, John C. Sih
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Patent number: 6440971Abstract: A binuclear DNA-threading transition metal complex with the general formula: (L1)-M1-(D1-B-D2)-M2-(L2) wherein D1-B-D2 is a bridging ligand; D1 is a polycyclic heteroaromatic ligand in which aza nitrogens can form a bidentate or tridentate chelate with Ml; D2 is any bi- or oligodentate ligand co-ordinated to the transition metal M2; B is any appropriately substituted chain of at least two atoms; M1 is a transition metal ion with octahedral co-ordination sphere; M2 is any transition metal ion; L1 comprises a set of 1-3 ancillary ligands that saturate the remaining co-ordination sphere of M1; and L2 comprises a set of 1-4 ancillary ligands that saturate the remaining co-ordination sphere of M2. An example of the complex according to the invention is shown in the FIG. 1. The complex according to the invention is useful for treatment of different diseases, such as cancer and infections.Type: GrantFiled: March 17, 2000Date of Patent: August 27, 2002Assignee: A+ Science Invest ABInventors: Per Lincoln, Bengt Nordén
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Publication number: 20020111489Abstract: A process for purifying 20(S)-camptothecin, the process comprising:Type: ApplicationFiled: January 17, 2002Publication date: August 15, 2002Inventors: Rainer Sobotta, Armin Rapp
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Patent number: 6420379Abstract: The present invention relates to alkynyl-substituted camptothecins of formula (I) wherein X, R1, R2 are as defined herein, and the pharmaceutically salts thereof. These compounds are useful in therapy as antitumor agents.Type: GrantFiled: November 20, 2000Date of Patent: July 16, 2002Assignee: Pharmacia & Upjohn S.p.A.Inventors: Ilaria Candiani, Angelo Bedeschi, Giuseppina Visentin, Maria Chiara Fagnola, Laura Capolongo
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Publication number: 20020081626Abstract: Methods and kits for determine arginine compounds are discussed. The methods and kits of the invention can be used for the diagnosis of arginine compound associated disorders.Type: ApplicationFiled: July 5, 2001Publication date: June 27, 2002Inventors: Rima Kaddurah-Daouk, Thomas W. Bell, Alisher B. Khasanov
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Patent number: 6410731Abstract: A method of synthesizing a compound having the formula via a cascade radical 4+1 annulation includes the step wherein the precursor or the precursor is reacted with an arylisonitrile having the formula wherein X is a radical precursor such as Cl, Br or I. R6 is preferably —Si(R8R9R10) or —(R7)Si(R8R9R10), wherein R7 is an alkylene group, an alkenylene group, or an alkynylene group; and R8, R9 and R10 are independently a C1-10 alkyl group, a C2-10 alkenyl group, a C2-10 alkynyl group, an aryl group or a —(CH2)NR11 group, wherein N is an integer within the range of 1 through 10 and R11 is a hydroxy group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, —SRc or a nitro group. R1-R4 can be broadly substituted. R5 is preferably a C1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group. R13 is preferably H, F or —CH3.Type: GrantFiled: November 30, 2000Date of Patent: June 25, 2002Assignees: University of Pittsburgh, University of Kentucky Research FoundationInventors: Dennis P. Curran, Bom David, Thomas G. Burke
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Patent number: 6407239Abstract: Aromatic camptothecin ester compounds having the formula: are described as well as formulations containing the compounds. Methods of treating cancer and/or tumors are also disclosed.Type: GrantFiled: December 22, 2000Date of Patent: June 18, 2002Assignee: The Stehlin Foundation For Cancer ResearchInventors: Zhisong Cao, Beppino C. Giovanella
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Patent number: 6407118Abstract: Derivatives of camptothecin are disclosed and are represented by the general formula: wherein when R2 is H, R1 is a C2-C4 alkyl group, a C5-C15 alkyl group, a C3-C8 cycloalkyl group, a C2-C15 alkenyl group or a C2-C15 epoxy group; and when R2 is a nitro group, R1 is a C1-C15 alkyl group, a C2-C15 alkenyl group, a C3-C8 cycloalkyl group, or an expoxy group. Processes for making these derivatives and for using them in cancer treatment are also disclosed.Type: GrantFiled: April 16, 2001Date of Patent: June 18, 2002Assignee: The Stehlin Foundation For Cancer ResearchInventors: Zhisong Cao, Beppino C. Giovanella
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Patent number: 6403604Abstract: (20S) esters of camptothecin analogs are provided. The compounds are (20S) esters of an aminoalkanoic acid or an imidoalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.Type: GrantFiled: March 1, 2001Date of Patent: June 11, 2002Assignee: California Pacific Medical CenterInventors: Li-Xi Yang, Xiandao Pan, Huijuan Wang
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Patent number: 6403603Abstract: 9-Amino-20(S)-camptothecin (I) is prepared by reducing 12-nitro-20(S)-camptothecin (II); converting the resulting 12-amino-20(S)-camptothecin (III) into a compound of formula (IV) wherein X is a group which can be reductively removed; reacting the compound of formula (IV) with a nitrating agent, to obtain thereby the corresponding 9-nitro-20(S)-camptothecin compound of formula (V) substituted at the 12-position by the group X; reducing in a single step the compound of formula (V), so obtaining the 9-amino-20(S)-camptothecin of formula (I); or reducing the compound of formula (V), so obtaining the corresponding 9-amino-20(S)-camptothecin compound of formula (VI) substituted at the 12-position by the group X and reductively removing the X group from the compound of formula (VI), so obtaining 9-amino-20(S)-camptothecin.Type: GrantFiled: August 2, 1994Date of Patent: June 11, 2002Assignee: Pharmacia & Upjohn S.p.A.Inventors: Angelo Bedeschi, Walter Cabri, Ilaria Candiani, Franco Zarini
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Patent number: 6388078Abstract: A camptothecin compound of the formula [XVIII]: wherein R4 is a lower alkanoyl group, R5 is an ethyl group, R7 is a —O(CH2)3NH2 group that may be protected by a —COOC(CH3)3 group, and R6, R8 and R9 are a hydrogen.Type: GrantFiled: July 5, 2001Date of Patent: May 14, 2002Assignee: Tanabe Seiyaku Company, LimitedInventors: Takayuki Kawaguchi, Sumihiro Nomura, Kenji Tsujihara
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Patent number: 6380193Abstract: A compound of formula I: or a pharmaceutically acceptable salt, hydrate, ester, solvate, prodrug, metabolite, stereoisomer, or mixtures thereof.Type: GrantFiled: September 1, 1998Date of Patent: April 30, 2002Assignee: Guilford Pharmaceuticals Inc.Inventors: Jia-He Li, Jie Zhang
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Publication number: 20020049324Abstract: Aromatic camptothecin ester compounds having the formula: 1Type: ApplicationFiled: December 22, 2000Publication date: April 25, 2002Inventors: Zhisong Cao, Beppino C. Giovanella
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Patent number: 6376617Abstract: Water soluble polymeric conjugates of camptothecin consist essentially of N-(2-hydroxypropyl)methacryloylamide units linked via a spacer group to a residue of a camptothecin such as irinotecan or its non-soluble metabolite, 7-ethyl-10-hydroxy-camptothecin. The conjugates possess enhance antitumor activity and decreased toxicity with respect to the free drug. A process for their preparation and the pharmaceutical compositions containing them are also described.Type: GrantFiled: June 3, 1999Date of Patent: April 23, 2002Assignee: Pharmacia & Upjohn S.p.A.Inventors: Francesco Angelucci, Gabriele Fachin, Valeria Caiolfa, Antonino Suarato
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Publication number: 20020045756Abstract: The present invention relates to a novel process for preparation of camptothecin and of its derivatives by convergent synthesis starting from a 3-(aminomethyl)quinoline derivative and 5-hydroxy-5-ethyl-6-oxo-5,6-dihydropyrancarboxylic acid and to the intermediates obtained.Type: ApplicationFiled: September 14, 2001Publication date: April 18, 2002Applicant: AVENTIS PHARMA S.A.Inventors: Stefanie Leue, Stephanie Garcon, Andrew-Elliot Greene, Yves Genisson, Patrick Leon
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Patent number: 6372906Abstract: A method of synthesizing 7-silyl camptothecins and 7-silyl homocamptothecins includes the step of mixing a camptothecin or a homocamptothecin having hydrogen at the C7 position with a silyl radical generator and a silyl radical precursor under conditions to generate a silyl radical. SiR1R2R3 wherein R1, R2 and R3 are independently a C1-10 alkyl group, a C2-10 alkenyl group, a C2-10 alkynyl group, an aryl group, —(CH2)mR11 or SiR12R13R14, wherein m is an integer within the range of 1 through 10 and R11 is a hydroxy group, an alkoxy group, an amino group, an alkylamino group, a dialkylamino group, F, Cl, a cyano group, —SRc or a nitro group, and wherein R12, R13 and R14 are independently the same or different an alkyl group or an aryl group.Type: GrantFiled: April 12, 2001Date of Patent: April 16, 2002Assignee: University of PittsburghInventors: Dennis P. Curran, Wu Du
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Patent number: 6365594Abstract: Heterocycle-condensed morphinoid derivatives of formula (I), or solvates or salts thereof, are potent and selective delta opioid agonists and antagonists and are useful as i.a. analgesics. Pharmaceutical compositions containing such compounds, the use of such compounds as therapeutic agents, a method of treatment comprising the administration of such compounds, and a process for the preparation of such compounds are also described.Type: GrantFiled: February 22, 1999Date of Patent: April 2, 2002Assignee: SmithKline Beecham S.p.A.Inventors: Giulio Dondio, Silvano Ronzoni, Pier Andrea Gatti, Davide Graziani
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Publication number: 20020032331Abstract: Water soluble polymeric conjugates of camptothecin consist essentially of N-(2-hydroxypropyl)methacryloylamide units linked via a spacer group to a residue of a camptothecin such as irinotecan or its non-soluble metabolite, 7-ethyl-10-hydroxy amptothecin. The conjugates possess enhance antitumor activity and decreased toxicity with respect to the free drug. A process for their preparation and the pharmaceutical compositions containing them are also described.Type: ApplicationFiled: June 3, 1999Publication date: March 14, 2002Inventors: FRANCESCO ANGELUCCI, GABRIELE FACHIN, VALERIA CAIOLFA, ANTONINO SUARATO
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Patent number: 6352996Abstract: Derivatives of camptothecin as represented by the general formula: are described, wherein when R1 is H, R. is a C2-C4 alkyl group, a C6-C15 alkyl group, a C3-C8 cycloalkyl group, a C2-C15 alkenyl group or a C2-C15 epoxy group; and when R2 is a nitro group or an amino group, R1 is a C1-C15 alkyl group, a C1-C15 alkenyl group, a C3-C8 cycloalkyl group, or an epoxy group. Liposomal prodrugs including these specific derivatives of camptothecin restrained by a liposomal delivery system are also described. Processes for making these prodrugs and for using them in cancer treatment are also disclosed.Type: GrantFiled: February 8, 2000Date of Patent: March 5, 2002Assignee: The Stehlin Foundation For Cancer ResearchInventors: Zhisong Cao, Beppino C. Giovanella
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Patent number: 6350756Abstract: (20S) esters of camptothecin analogs are provided. The compounds are (20S) esters of an oxyalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.Type: GrantFiled: March 1, 2001Date of Patent: February 26, 2002Assignee: California Pacific Medical CenterInventors: Li-Xi Yang, Xiandao Pan, Huijuan Wang
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Publication number: 20020019343Abstract: 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: ApplicationFiled: August 20, 2001Publication date: February 14, 2002Inventor: Felix Kratz
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Patent number: 6339091Abstract: The compound of the formula wherein the substituents are defined as in the specification and its non-toxic, pharmaceutically acceptable salts which are useful for the treatment of viral infections, parasitic diseases and the treatment of cancer.Type: GrantFiled: June 14, 1999Date of Patent: January 15, 2002Assignee: Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)Inventors: Dennis Bigg, Olivier Lavergne, Francesc Pla Rodas, Jacques Pommier, Gerard Ulibarri, Jerry Harnett, Alain Rolland, Anne-Marie Liberatore, Christophe Lanco, Jean-Bernard Cazaux, Christine Le Breton, Eric Manginot
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Publication number: 20010051724Abstract: The present invention relates to a process for preparing camptothecin and camptothecin analogs of Formula (I) from compounds of Formula (II) and to novel intermediates useful in their preparation, 1Type: ApplicationFiled: July 11, 2001Publication date: December 13, 2001Applicant: Gilead Sciences, Inc.Inventors: Francis Gerard Fang, Shiping Xie
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Patent number: 6328953Abstract: The invention relates to polymeric conjugates of 20-O-[glycyl-aminoacyl-glycyl]-camptothecins and a process for producing the same.Type: GrantFiled: March 31, 2000Date of Patent: December 11, 2001Assignee: Pharmacia & Upjohn S.p.A.Inventors: Francesco Angelucci, Fabrizio Orzi, Gabriele Fachin, Valeria Caiolfa, Moreno Zamai, Antonino Suarato
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Patent number: 6306868Abstract: Compounds of formula (I), wherein: R1 is —CN, —CH(CN)—R4, —CH═C(CN)—R4, —CH2—CH(CN)—R4, —C(═NOH)—NH2, —C(═NH)—NH2, —CH═C(NO2)—R4, —CH(CN)—R5, —CH(CH2NO2)—R5; 5-tetrazolyl, 2-(4,5-dihydrooxazolyl), 1,2,4-oxadiazolin-3-yl-5-one; R2 is hydrogen; R3 is hydrogen, OR6; R4 is hydrogen, C1-C6 linear or branched alkyl, CN, COOR7; R5 is hydrogen, OR8; R6 is hydrogen, C1-C6 linear or branched alkyl, (C6-C12) aryl (C1-C4) alkyl, (C1-C4) alkoxy (C1-C4) alkyl, (C1-C4) alkyl (C6-C12) aryl, (C6-C12) aryl (C2-C4) acyl, (C2-C4) acyl, amino (C1-C4) alkyl, amino (C2-C4) acyl, glycosyl; R7 is hydrogen, C1-C6 linear or branched alkyl, (C6-C12) aryl (C1-C4) alkyl, (C1-C4) alkoxy (C1-C4) alkyl, (C1-C4) alkyl (C6-C12) aryl; R8 has the same meanings of R6, independently of the latter. These compounds are active as topoisomerase I inhibitors and can be used as antitumor drugs.Type: GrantFiled: August 22, 2000Date of Patent: October 23, 2001Assignee: Istituto Nazionale per Lo Studio e la Cura Dei TumoriInventors: Lucio Merlini, Sergio Penco, Franco Zunino
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Publication number: 20010031761Abstract: Derivatives of camptothecin are disclosed and are represented by the general formula: 1Type: ApplicationFiled: December 26, 2000Publication date: October 18, 2001Inventors: Zhisong Cao, Beppino C. Giovanella
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Patent number: 6291447Abstract: Novel granulatimide compounds and pharmaceutical formulations thereof are provided.Type: GrantFiled: February 26, 1999Date of Patent: September 18, 2001Assignees: The University of British Columbia, Kinetek Pharmaceuticals, Inc.Inventors: Raymond Andersen, Michel Roberge, Jasbinder Sanghera, Daniel Leung, Edward Piers, Roberto GS Berlinck, Robert Britton
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Patent number: 6291676Abstract: Camptothecin and homocamptothecin analogs and derivatives are provided incorporating alkylamine and polyalkylamine moieties.Type: GrantFiled: March 2, 2000Date of Patent: September 18, 2001Assignee: University of Kentucky Research FoundationInventors: Thomas G. Burke, Ayhan S. Demir, Cihangir Tanyeli, Ashok J. Chavan, Tie-Lin Wang, Yves Pommier
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Patent number: 6288072Abstract: &bgr;-Alanine esters of camptothecin compounds which are effective anti-tumor compounds are disclosed. These compounds inhibit the enzyme topoisomerase I and may alkylate DNA of the associated topoisomerase I-DNA cleavable complex.Type: GrantFiled: December 29, 1999Date of Patent: September 11, 2001Inventors: Monroe E. Wall, Mansukh C. Wani, Govindarajan Manikumar, Neelakantan Balasubramanian, Dolatrai Vyas
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Patent number: 6255317Abstract: The present invention provides a cholesterol biosynthesis inhibitor which specifically inhibits the sterol 14-reductase which is involved in the distal pathway of cholesterol biosynthesis, a compound of formula (1) below and the use of an extract or the compound of formula (1) for treating hypercholesterolaemia or hyperlipidaemia. The inhibitor comprises an extract obtained by extracting Corydalis Turtschaninowii Besser with a solvent, or an organic layers obtained by partitioning an extract from Corydalis Turtschaninowii Besser with an organic solvent. The extract contains 7,8,13,13&agr;-tetrahydrocoridaline or its derivative, as the active ingredients, which specifically inhibits the enzyme which is involved in the distal pathway of the cholesterol biosynthesis.Type: GrantFiled: January 20, 1999Date of Patent: July 3, 2001Assignee: Hanwha Chemical CorporationInventors: Jung Ho Kim, Tae Neung Jhong, Young Ki Paik, Joon Seo Park, Eui Deok Kim, You Suk Lee, Seung Un Kim
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Publication number: 20010003779Abstract: A method of synthesizing a compound having the formula 1Type: ApplicationFiled: November 30, 2000Publication date: June 14, 2001Inventors: Dennis P. Curran, Bom David, Thomas G. Burke
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Patent number: 6242604Abstract: A process for preparing a morphinan derivative, by providing a dihydrofuranyl bridged tetracycle halide of the formula (19) wherein X is halogen, R is an alkyl group of from 1 to about 10 carbon atoms, and R1 is a protecting group; and converting the pentacycle halide into a morphinan derivative of formula (20) wherein R is as defined above.Type: GrantFiled: August 11, 2000Date of Patent: June 5, 2001Assignee: Mallinckrodt Inc.Inventors: Tomas Hudlicky, Gabor Butora
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Patent number: 6242457Abstract: Camptothecin derivatives of camptothecin of formula (I) wherein the groups R1, R2 and R3 are as defined in the description are disclosed. The compounds of formula (I) are endowed with antitumor activity and show a good therapeutic index. Processes for the preparation of the compounds of formula (I) and their use in the preparation of medicaments useful in the treatment of tumors, viral infections and antiplasmodium falciparum are also disclosed.Type: GrantFiled: February 22, 2000Date of Patent: June 5, 2001Assignees: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Istituo Nazionale per lo Studio e la Cura dei TumoriInventors: Sergio Penco, Lucio Merlini, Paolo Carminati, Franco Zunino
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Patent number: 6239139Abstract: The present invention provides a cholesterol biosynthesis inhibitor which specifically inhibits the sterol 14-reductase which is involved in the distal pathway of cholesterol biosynthesis, a compound of formula (1) below and the use of an extract or the compound of formula (1) for treating hypercholesterolaemia or hyperlipidaemia. The inhibitor comprises an extract obtained by extracting Corydalis Turtschaninowii Besser with a solvent, or an organic layers obtained by partitioning an extract from Corydalis Turtschaninowii Besser with an organic solvent. The extract contains 7,8,13,13&agr;-tetrahydrocoridaline or its derivative, as the active ingredients, which specifically inhibits the enzyme which is involved in the distal pathway of the cholesterol biosynthesis.Type: GrantFiled: January 20, 1999Date of Patent: May 29, 2001Assignee: Hanwha Chemical CorporationInventors: Jung Ho Kim, Tae Neung Jhong, Young Ki Paik, Joon Seo Park, Eui Deok Kim, You Suk Lee, Seung Un Kim