The Chalcogen Is Bonded Directly To A Ring Carbon Of The Five-membered Hetero Ring Which Is Adjacent To The Ring Nitrogen (e.g., 2-indolinones, Etc.) Patents (Class 548/486)
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Patent number: 6794395Abstract: The present invention relates to substituted indolinones of general formula wherein R1 to R6 and X are defined as in claim 1, the isomers and the salts thereof, in particular the physiologically acceptable salts thereof which have valuable pharmacological properties, especially an inhibitory effect on various receptor-tyrosine kinases, and cycline/CDK complexes as well as on the proliferation of endothelial cells and various tumor cells, pharmaceutical compositions containing these compounds, their use and processes for preparing them.Type: GrantFiled: July 22, 2002Date of Patent: September 21, 2004Assignee: Boehringer Ingelheim Pharma GmbH & Co. KGInventors: Gerald Juergen Roth, Armin Heckel, Rainer Walter, Ulrike Tontsch-Grunt, Walter Spevak, Jacobus C. A. Van Meel
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Patent number: 6765012Abstract: The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.Type: GrantFiled: September 27, 2002Date of Patent: July 20, 2004Assignee: Allergan, Inc.Inventors: Steven W. Andrews, Julie A. Wurster, Edward H. Wang, Thomas Malone
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Patent number: 6762180Abstract: Indolinones of the formula having an inhibitory effect on receptor tyrosine kinases and cyclin/CDK complexes, as well as on the proliferation of endothelial cells and various tumor cells. Exemplary are: (a) 3-Z-[1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (b) 3-Z-[(1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone, and (c) 3-Z-[1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-metboxycarbonyl-2-indolinone.Type: GrantFiled: October 3, 2000Date of Patent: July 13, 2004Assignee: Boehringer Ingelheim Pharma KGInventors: Gerald Juergen Roth, Armin Heckel, Rainer Walter, Jacobus Van Meel, Norbert Redemann, Ulrike Tontsch-Grunt, Walter Spevak, Frank Hilberg
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Patent number: 6750241Abstract: Disclosed are compounds which inhibit or modulate the activity of protein kinases and pharmaceutical compositions containing such compounds. The disclosed compound contain two or more ligand moieties covalently linked together by one or more linking groups. Such compounds are useful for treating diseases or medical disorders mediated by protein kinases.Type: GrantFiled: March 6, 2002Date of Patent: June 15, 2004Assignee: Theravance, Inc.Inventors: John H. Griffin, Yu-Hua Ji, Edmund J. Moran, Jonathan W. Wray
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Publication number: 20040082615Abstract: This invention is directed to indolone derivatives which are selective antagonists for the GalR3 receptor. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition made by combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject's depression and/or anxiety.Type: ApplicationFiled: August 7, 2003Publication date: April 29, 2004Inventors: Michael Konkel, John M. Wetzel, Jamie Talisman
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Patent number: 6716870Abstract: The present invention is directed to prodrugs of certain 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that modulate the activity of protein kinases (“PKs”). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.Type: GrantFiled: September 16, 2002Date of Patent: April 6, 2004Assignees: Sugen, Inc., Pharmacia & Upjohn CompanyInventors: Malcolm Wilson Moon, Walter Morozowich, Ping Gao, Marcel Koenig
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Patent number: 6713651Abstract: Disclosed are multibinding compounds which are &bgr;2-adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma, and bronchitis. They are also useful in the treatment of nervous system injury and premature labor.Type: GrantFiled: November 1, 2000Date of Patent: March 30, 2004Assignee: Theravance, Inc.Inventors: Edmund J. Moran, Seok-Ki Choi
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Patent number: 6706890Abstract: The invention relates to a method for producing 2-oxindoles from the corresponding isatines of formula (I), wherein R can be H, CH3, phenyl or benzyl and R1 can be H, C1-C4-alkyl, C1-C4-alkoxy, phenyl phenoxy, halogen, amino, nitro or hydroxy. Said isatines are converted by means of hydrazine hydrate in a polar solvent at a temperature of 15 to 185° C. to form a corresponding isatine hydrazone which directly undergoes further reaction to form the corresponding 2-oxindole of formula (II) by adding diazabicyclooctane and/or diazabicycloundecane and/or ethyldiisopropylamine as a catalyst in temperatures of 100 to 185° C., whereby the produced reaction water is distilled off. According to formula (II), R and R1 have the aforementioned definitions. The 2-oxindole is isolated from the reaction mixture by distilling off the solvent and by means of crystallisation.Type: GrantFiled: June 26, 2002Date of Patent: March 16, 2004Assignee: DSM Fine Chemicals Austria Nfg GmbH & Co KGInventors: Wolfram Hendel, Ulfried Felfer, Karl Schwendinger
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Patent number: 6696482Abstract: The present invention features formulations, including liquid, semi-solid or solid pharmaceutical formulations, that improve the oral bioavailability of hydrophobic pharmaceutical agents, such as quinazoline-, nitrothiazole-, and indolinone-based compounds. Also featured are formulations for parenteral delivery of such hydrophobic pharmaceutical agents, as well as methods of making and using both types of formulations.Type: GrantFiled: March 5, 2001Date of Patent: February 24, 2004Assignee: Sugen, Inc.Inventors: Narmada Shenoy, Gregory S. Wagner
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Patent number: 6692538Abstract: The invention relates to the use of novel indole compounds as direct dyes in compositions intended for dyeing keratin materials, and, for example, compositions intended for dyeing human keratin fibers and including the hair, and in cosmetic compositions intended for making up the skin, the nails and the lips, to the dye compositions or make-up compositions comprising them and to the direct dyeing process using them, and processes of manufacturing said novel indole compounds.Type: GrantFiled: May 3, 2002Date of Patent: February 17, 2004Assignee: L'Oréal S.A.Inventors: Nicole Bonaventure, Patrick Gilard, Gilles Barre, Michel Dubois
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Patent number: 6693202Abstract: Disclosed are multibinding compounds which are muscarinic receptor antagonists. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is, independently of each other, a muscarinic receptor antagonist or an allosteric modulator provided that at least one of said ligand is a muscarinic receptor antagonist. The multibinding compounds of this invention are useful in the treatment and prevention of diseases such as chronic obstructive pulmonary disease, chronic bronchitis, irritable bowel syndrome, urinary incontinence, and the like.Type: GrantFiled: August 25, 2000Date of Patent: February 17, 2004Assignee: Theravance, Inc.Inventors: James Aggen, John H. Griffin, Mathai Mammen, Daniel Marquess, Edmund J. Moran, David Oare
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Patent number: 6689806Abstract: The invention relates to certain indolinone compounds, their method of synthesis, and a combinatorial library consisting of the indolinone compounds of the invention. The invention also relates to methods of modulating the function of protein kinases using indolinone compounds of the invention and methods of treating diseases by modulating the function of protein kinases and related signal transduction pathways.Type: GrantFiled: March 22, 2000Date of Patent: February 10, 2004Assignee: Sugen, Inc.Inventors: Peng Cho Tang, Li Sun, Gerald McMahon, Todd Anthony Miller, Shahrzad Shirazian, Chung Chen Wei, G. Davis Harris, Jr., Xiaoyuan Li, Congxin Liang
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Patent number: 6683101Abstract: Described are heterocycle-substituted cyclohexylamines of formula (I), and their pharmaceutically acceptable salts thereof.Type: GrantFiled: December 3, 2002Date of Patent: January 27, 2004Assignee: Warner-Lambert CompanyInventors: Russell Joseph Deorazio, Sham Shridhar Nikam, Ian Leslie Scott, Brian Alan Sherer, Lawrence David Wise
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Patent number: 6683115Abstract: Disclosed are multibinding compounds which are &bgr;2 adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma, bronchitis. They are also useful in the treatment of nervous system injury and premature labor.Type: GrantFiled: August 21, 2001Date of Patent: January 27, 2004Assignee: Theravance, Inc.Inventors: Edmund J. Moran, Seok-Ki Choi
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Publication number: 20040014986Abstract: The invention relates to a method for producing 2-oxindoles from the corresponding isatines of formula (I), wherein R can be H, CH3, phenyl or benzyl and R1 can be H, C1-C4-alkyl, C1-C4-alkoxy, phenyl, phenoxy, halogen, amino, nitro or hydroxy. Said isatines are converted by means of hydrazine hydrate in a polar solvent at a temperature of 15 to 185° C. to form a corresponding isatine hydrazone which directly undergoes further reaction to form the corresponding 2-oxindole of formula (II) by adding diazabi-cyclooctane and/or diazabicycloundecane and/or ethyldiisopropylamine as a catalyst in temperatures of 100 to 185° C., whereby the produced reaction water is distilled off. According to formula (II), R and R1 have the aforementioned definitions. The 2-oxindole is isolated from the reaction mixture by distilling off the solvent and by means of crystallisation.Type: ApplicationFiled: June 26, 2002Publication date: January 22, 2004Inventors: Wolfram Hendel, Ulfried Felfer, Karl Schwendinger
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Patent number: 6673790Abstract: The present invention relates to novel indolin-2-one derivatives of formula: to the preparation and to the pharmaceutical compositions comprising them. These compounds have an affinity for oxytocin receptors.Type: GrantFiled: October 2, 2002Date of Patent: January 6, 2004Assignee: Sanofi-SynthelaboInventors: Loïc Foulon, Georges Garcia, Claudine Serradeil-Le Gal, Gérard Valette
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Patent number: 6642251Abstract: The present invention relates to novel geometrically restricted 2-indolinones and physiologically acceptable salts thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.Type: GrantFiled: January 15, 2003Date of Patent: November 4, 2003Assignee: Sugen, Inc.Inventors: Peng Cho Tang, Todd Anthony Miller, Li Sun, Ngoc My Tran, Asaad Nematalla, Anh Thi Nguyen
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Patent number: 6638965Abstract: Indolinones of general formula I which are inhibitors of cell proliferation, particularly of tumour cells, and inhibitors of protein kinases. The following compounds are exemplary: (Z)-3-{1-[4-(N-(2-aminoethyl)-N-methylsulphonyl-amino)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(N-(2-dimethylaminoethyl)-N-phenylsulphonyl-amino)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, and (Z)-3-{1-[4-(4-methylpiperazinomethyl)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone.Type: GrantFiled: November 1, 2001Date of Patent: October 28, 2003Assignee: Boehringer Ingelheim Pharma KGInventors: Rainer Walter, Armin Heckel, Gerald Roth, Joerg Kley, Gisela Schnapp, Martin Lenter, Jacobus Van Meel, Walter Spevak, Ulrike Weyer-Czernilofsky
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Patent number: 6624171Abstract: Substituted aza-oxindole derivatives useful as cyclin dependent kinase 11 inhibitors, for preventing/reducing the severity of epithelial cytotoxicity side-effects (e.g., alopecia, plantar-palmar syndrome, mucositis) induced by chemoptherapy and/or radiation therapy in a patient receiving such therapy.Type: GrantFiled: August 28, 2001Date of Patent: September 23, 2003Assignee: SmithKline Beecham CorporationInventors: Philip Anthony Harris, Lee Frederick Kuyper, Karen Elizabeth Lackey, James Marvin Veal
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Patent number: 6593497Abstract: The present invention is directed to multibinding compounds which are &bgr;2 adrenergic receptor agonists and are therefore useful in the treatment and prevention of respiratory diseases such asthma, bronchitis, and the like. They are also useful in the treatment of nervous system injury and premature labor.Type: GrantFiled: February 14, 2000Date of Patent: July 15, 2003Assignee: Theravance, Inc.Inventors: Seok-Ki Choi, Edmund J. Moran
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Patent number: 6586471Abstract: The present invention contains halogenated 2-amino-3,4 heptenoic acid derivatives useful as nitric oxide synthase inhibitors.Type: GrantFiled: April 13, 2001Date of Patent: July 1, 2003Assignee: G. D. SearleInventors: Donald W. Hansen, Jr., Barnett S. Pitzele, Ronald Keith Webber, Mihaly V. Toth, Pamela T. Manning, Alok K. Awasthi, Mahima Trivedi
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Patent number: 6583294Abstract: A process for the preparation of methyl 2-(3-chloropropoxy)-indole-3-carboxylate, which comprises reacting a 3-chloro-3-carboxylate indole compound with 3-chloropropanol in the presence of an acid having a pKa of from 0 to 2.Type: GrantFiled: December 3, 2002Date of Patent: June 24, 2003Assignee: SmithKline Beecham p.l.c.Inventors: Michael Fedouloff, John Bryce Strachan
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Publication number: 20030114683Abstract: The invention relates to compounds of formula: 1Type: ApplicationFiled: July 24, 2002Publication date: June 19, 2003Inventors: Richard Roux, Claudine Serradeil-Le Gal, Bernard Tonnerre, Jean Wagnon
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Patent number: 6576656Abstract: An oxindole of Formula 1 or a prodrug thereof, or a pharmaceutically acceptable salt thereof is useful for growth hormone releaser: wherein R1, R2, R3 and R4 are independently hydrogen, optionally substituted alkyl etc; R5 is optionally substituted aryl or optionally substituted heteroaryl; Z is —O— or —NH—; one of W1 and W2 is hydrogen, alkyl or —Y—CON(R10)R11; the other of W1 and W2 is n is 1, 2 or 3; m is 0, 1, 2 or 3; Y is single bond or C1-C3 alkylene; R6 and R7 are independently hydrogen, optionally substituted alkyl etc; R8 and R9 are independently hydrogen, optionally substituted alkyl etc; R10 and R11 are independently hydrogen, alkyl etc.Type: GrantFiled: March 22, 2001Date of Patent: June 10, 2003Assignee: Sumitomo Pharmaceuticals Co., Ltd.Inventors: Teruhisa Tokunaga, Takashi Umezome, W. Ewan Hume, Ryu Nagata, Kazuhiko Okazaki, Yasuyuki Ueki, Kazuo Kumagai
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Patent number: 6562857Abstract: This invention provides a progesterone receptor agonist of formula 1 having the structure wherein T is O, S, or absent; R1, and R2 are each, independently, hydrogen, alkyl, substituted alkyl; or R1 and R2 are taken together form a ring and together contain —CH2(CH2)nCH2—, —CH2CH2CMe2CH2CH2—, —O(CH2)pCH2—, —O(CH2)qO—, —CH2CH2OCH2CH2—, or —CH2CH2NR7CH2CH2—; n=1-5; p=1-4; q=1-4; R3 is hydrogen, OH, NH2, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or CORA; RA is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R4 is hydrogen, halogen, CN, NH2, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R5 is hydrogen, alkyl, or substituted alkyl; R6 is hydrogen, alkyl, substituted alkyl, or CORB, RB is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoType: GrantFiled: January 9, 2002Date of Patent: May 13, 2003Assignee: WyethInventors: Mark A. Collins, Valerie A. Mackner, Jay E. Wrobel, Lin Zhi, Todd K. Jones, James P. Edwards, Christopher M. Tegley
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Publication number: 20030069430Abstract: Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by canType: ApplicationFiled: November 30, 2001Publication date: April 10, 2003Inventors: Stephen Thomas Davis, Scott Howard Dickerson, Stephen Vernon Frye, Philip Anthony Harris, Robert Neil Hunter, Lee Frederick Kuyper, Karen Elizabeth Lackey, Michael Joseph Luzzio, James Marvin Veal, Duncan Herrick Walker
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Publication number: 20030069299Abstract: Indolinones of general formula I 1Type: ApplicationFiled: November 1, 2001Publication date: April 10, 2003Inventors: Rainer Walter, Armin Heckel, Gerald Roth, Joerg Kley, Gisela Schnapp, Martin Lenter, Jacobus Van Meel, Walter Spevak, Ulrike Weyer-Czernilofsky
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Patent number: 6541669Abstract: Disclosed are multibinding compounds which are &bgr;2 adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma, bronchitis. They are also useful in the treatment of nervous system injury and premature labor.Type: GrantFiled: June 2, 1999Date of Patent: April 1, 2003Assignee: Theravance, Inc.Inventors: Edmund J. Moran, Seok-Ki Choi
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Patent number: 6531502Abstract: The present invention relates to novel 3-methylidenyl-2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.Type: GrantFiled: February 5, 2001Date of Patent: March 11, 2003Assignee: Sugen, Inc.Inventors: Pen Cho Tang, Li Sun, Todd Anthony Miller, Congxin Liang, Ngoc My Tran, Anh Thi Nguyen, Asaad Nematalla
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Patent number: 6528658Abstract: A series of steps of (A) a step for bringing a cycloalkane into contact with molecular oxygen (oxidizing reactor 2) in the presence of an oxidizing catalyst having an imide unit of the following formula (I): wherein X represents oxygen atom or hydroxyl group; (B) a step for separating the catalyst, and by-produced acid component or a derivative thereof from the reaction mixture (filter 3, extracting column 4, hydrolyzing unit 7, saponifying unit 8); and (C) steps for separating the cycloalkane, a cycloalkanol, and a cycloalkanone from the reaction mixture individually (distilling columns 5, 6, 9, and 10) makes it possible to produce cycloalkanones efficiently. A first component (lower-boiling point component) containing the cycloalkane and a second component (higher-boiling point component) containing the cycloalkanone and cycloalkanol may be separated from the reaction mixture, and the cycloalkanone and the cycloalkanol may be separated from the higher-boiling point component.Type: GrantFiled: October 18, 2000Date of Patent: March 4, 2003Assignee: Daicel Chemical Industries, Ltd.Inventors: Hiroyuki Miura, Hitoshi Watanabe, Tomohide Ina, Hidehiko Nakajima
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Patent number: 6525072Abstract: The present invention relates to novel geometrically restricted 2-indolinones and physiologically acceptable salts thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.Type: GrantFiled: August 30, 1999Date of Patent: February 25, 2003Assignee: Sugen, Inc.Inventors: Peng Cho Tang, Todd Anthony Miller, Li Sun, Ngoc My Tran, Asaad Nematalla, Anh Thi Nguyen
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Patent number: 6521657Abstract: This invention relates to compounds which are agonists of the progesterone receptor which have the general structure: wherein: R1, R2, R3, R4, R5 and Q1 are as defined herein, or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.Type: GrantFiled: October 30, 2001Date of Patent: February 18, 2003Assignees: Wyeth, Ligand Pharmaceuticals, Inc.Inventors: Andrew Fensome, Puwen Zhang, Marci C. Koko, Lin Zhi, Todd K. Jones, Jay E. Wrobel, Christopher M. Tegley, James P. Edwards, Edward G. Melenski
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Patent number: 6506763Abstract: The present invention relates to novel 3-(substituted)-2-indolinones compounds and physiologically acceptable salts and prodrugs thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related disorders such as cancer.Type: GrantFiled: July 30, 2001Date of Patent: January 14, 2003Assignee: Sugen, Inc.Inventors: Peng Cho Tang, Li Sun, Gerald McMahon
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Patent number: 6504034Abstract: Disclosed are novel naphthostyrils of formula These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. These compounds and their pharmaceutically acceptable salts and esters are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer. Also disclosed are pharmaceutical compositions containing such compounds, methods for the treatment and/or prevention of cancer using such compositions, and intermediates useful in the preparation of the compounds of formula I.Type: GrantFiled: January 10, 2002Date of Patent: January 7, 2003Assignee: Hoffmann-La Roche Inc.Inventors: Yi Chen, Apostolos Dermatakis, Frederick Martin Konzelmann, Jin-Jun Liu, Kin-Chun Luk
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Publication number: 20030004351Abstract: Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-Cl1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydmogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cType: ApplicationFiled: August 8, 2001Publication date: January 2, 2003Inventors: Stephen Thomas Davis, Scott Howard Dickerson, Stephen Vernon Frye, Philip Anthony Harris, Robert Neil Hunter, Lee Frederick Kuyper, Karen Elizabeth Lackey, Michael Joseph Luzzio, James Marvin Veal, Duncan Herrick Walker
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Patent number: 6500854Abstract: A chondrogenesis promoter comprising as an active ingredient a compound represented by general formula (I) or a salt thereof: wherein R1 represents a halogen atom, a lower alkyl group, a lower alkoxy group, etc.; R2 represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, an acyl group, an aryl group, a heterocyclic group, etc.; R1 represents a lower alkyl group, a cycloalkyl group, an aryl group, a heterocyclic group, etc.; R4 represents a hydrogen atom, a lower alkyl group, an aryl group, a heterocyclic group, etc.; X and Y represent —CH2—, —NH—or —O—; and n represents an integer of 0-4.Type: GrantFiled: September 21, 2001Date of Patent: December 31, 2002Assignee: Chugai Sei Yaku Kabushiki KaishaInventors: Hidetomo Kitamura, Atsuhiko Kato, Toru Esaki
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Patent number: 6482848Abstract: The present invention is directed to prodrugs of certain 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that modulate the activity of protein kinases (“PKs”). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.Type: GrantFiled: May 24, 2001Date of Patent: November 19, 2002Assignee: Sugen IncorporatedInventors: Malcolm Wilson Moon, Walter Morozowich, Ping Gao, Marcel Koenig
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Patent number: 6469181Abstract: The present invention provides a processes, having practical utility, for preparing 2-oxindoles, N-hydroxy-2-oxindoles, or mixtures thereof comprising: catalytically hydrogenating a 2-nitroarylmalonate diester to produce a 2-(N-hydroxyamino)arylmalonate diester, a 2-aminoarylmalonate diester, or mixtures thereof as a first reaction intermediate; cyclizing, by intramolecular aminolysis of one ester group, the first reaction intermediate to produce a N-hydroxy-2-oxindole-3-carboxylate ester, 2-oxindole-3-carboxylate ester, or mixtures thereof as a second reaction intermediate; and hydrolyzing and decarboxylating the remaining ester group of the second reaction intermediate to produce the N-hydroxy-2-oxindole, the 2-oxindole, or mixtures thereof, wherein the cyclization reaction and the hydrolysis and decarboxylation reaction are conducted in situ with the catalytic hydrogenation reaction without isolation of said reaction intermediates.Type: GrantFiled: January 30, 1995Date of Patent: October 22, 2002Assignee: Catalytica, Inc.Inventors: John M. Gruber, A. Ray Bulls, John H. Grate
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Patent number: 6414153Abstract: Novel compounds of the formula I: which are useful for treating or preventing inflammatory and immune cell-mediated diseases. Exemplary compounds are: 3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-1,3-dihydroindol-2-one; 3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-1,3-dihydro-indol-2-one; 3-benzyl-1-(3,5-dichlorophenyl)-3-methyl-1,3-dihydroindol-2-one; 3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-4-hydroxy-3-methyl-1,3-dihydroindol-2-one; and, 3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-5-fluoro-1,3-dihydroindol-2-one.Type: GrantFiled: June 28, 2000Date of Patent: July 2, 2002Assignee: Boehringer Ingelheim Pharmaceuticals, Inc.Inventors: Terence Alfred Kelly, Jiang-Ping Wu, Daniel Kuzmich, Yancey David Ward, Leah Lynn Frye
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Patent number: 6355666Abstract: In accordance with the present invention, there are provided normal modified forms of nonsteroidal anti-inflammatory drugs. Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.Type: GrantFiled: June 23, 2000Date of Patent: March 12, 2002Assignee: Medinox, Inc.Inventors: Ching-San Lai, Tingmin Wang
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Patent number: 6350754Abstract: The present invention relates to novel 3-(cycloalkano-heteroarylidenyl)-2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which are expected to modulate the activity of protein tyrosine kinases and therefore to be useful in the prevention and treatment of protein tyrosine kinase related cellular disorders such as cancer.Type: GrantFiled: January 12, 2000Date of Patent: February 26, 2002Assignee: Sugen, Inc.Inventors: Peng Cho Tang, Li Sun, Gerald McMahon
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Patent number: 6329550Abstract: The present application relates to novel aminomalonamides of the formula and pharmaceutical composition thereof which are useful for inhibiting matrix metalloproteinases.Type: GrantFiled: December 17, 1999Date of Patent: December 11, 2001Assignee: Aventis Pharmaceuticals Inc.Inventors: Alan M. Warshawsky, Michael J. Janusz
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Patent number: 6319918Abstract: Substituted indolinones of general formula having effect on various kinases and cycline/CDK complexes and on the proliferation of various tumour cells. Exemplary compounds are: 3-Z-[1-(4-(N-Benzyl-N-methyl-aminomethyl)-phenylamino)-1-methyl-methylene]-5-amido-2-indolinone and 3-Z-[1-(4-(2,3,4,5-Tetrahydro-benzo(d)azepin-3-yl-methyl)-phenylamino)-1-methyl-methylene]-5-amido-2-indolinone.Type: GrantFiled: June 1, 1999Date of Patent: November 20, 2001Assignee: Boehringer Ingelheim Pharma KGInventors: Armin Heckel, Rainer Walter, Wolfgang Grell, Jacobus C. A. van Meel, Norbert Redemann
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Patent number: 6313310Abstract: Disclosed are 4- and 5-alkynyloxindoles as well as 4- and 5-alkenyloxindoles that inhibit or modulate protein kinases, in particular JNK protein kinases. The compounds of the invention and their pharmaceutically acceptable salts, and prodrugs of said compounds, are useful as anti-inflammatory agents, particularly useful in the treatment of rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing the foregoing compounds, methods for the treatment and/or control of inflammation, particularly in the treatment or control of rheumatoid arthritis using these compounds, as well as intermediates useful in the preparation of compounds of the invention.Type: GrantFiled: December 15, 1999Date of Patent: November 6, 2001Assignee: Hoffmann-La Roche Inc.Inventors: Kin-Chun Luk, Paige E. Mahaney, Steven Gregory Mischke
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Patent number: 6306378Abstract: This invention relates to a two-part system useful for treating proteinaceous substrates. The two-part system has a first part comprising a water-soluble/dispersible reactive polyimido compound and a second part comprising a nucleophilic catalytic agent. The polyimido compounds may be selected from the group consisting of polysuccinimide compounds, polyglutimide compounds, and copolymers of thereof. The polyimido compound may also comprise a functionalizing moiety that provides functionality to the polyimido compound and is preferably derived from a nucleophilic moiety selected from the group consisting of amines, alcohols, phenols, thiols, and carboxylates; and a water-solubilizing/dispersing moiety that provides water-solubility and/or water-dispersibility to the polyimido compound and is preferably derived from a nucleophilic moiety selected from the group consisting of amines, alcohols, phenols, thiols, and carboxylates.Type: GrantFiled: April 7, 1999Date of Patent: October 23, 2001Assignee: National Starch & Chemical Investment Holding Corp.Inventors: Jacob J. Guth, Samuel A. Vona, Jr., John S. Thomaides, Ann C. Savoca
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Patent number: 6307056Abstract: Disclosed are 4-aryloxindoles that inhibit or modulate protein kinases, in particular JNK protein kinases. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are useful as anti-inflammatory agents, particularly useful in the treatment of rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing the foregoing compounds, as well as methods for the treatment and/or control of inflammation, particularly in the treatment or control of rheumatoid arthritis, using said compounds.Type: GrantFiled: December 15, 1999Date of Patent: October 23, 2001Assignee: Hoffman-La Roche Inc.Inventors: Wendy Lea Corbett, Kin-Chun Luk, Paige E. Mahaney
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Patent number: 6303793Abstract: Disclosed are novel 4-alkenyl- and 4-alkynyl oxindoles having the formula and the pharmaceutically acceptable salts thereof, wherein R1, R2, R3, a, b, and X are as defined herein. These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer, more particularly, the treatment or control of breast and colon tumors. Also disclosed are pharmaceutical compositions containing the compounds of formula I and II as well as intermediates useful in the preparation of the compounds of formula I and II.Type: GrantFiled: May 5, 2000Date of Patent: October 16, 2001Assignee: Hoffmann-La Roche Inc.Inventors: Yi Chen, Apostolos Dermatakis, Jin-Jun Liu, Kin-Chun Luk
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Patent number: 6300504Abstract: This invention relates to water-soluble/dispersible reactive imido and polyimido compounds, wherein the polyimido compounds may be selected from the group consisting of polysuccinimide compounds, polyglutimide compounds, and copolymers of thereof. The polyimido compounds comprise a water-solubilizing/dispersing moiety that provides water-solubility and/or water-dispersibility to the polyimido compound and preferably is derived from a nucleophilic moiety selected from the group consisting of amines, alcohols, phenols, thiols, and carboxylates. The present invention also pertains to a proteinaceous substrate to which the imido or polyimido compound has been covalently bonded and to a method for treating a proteinaceous substrate with the imido or polyimido compound.Type: GrantFiled: December 22, 1998Date of Patent: October 9, 2001Assignee: National Starch & Chemical Investment Holding Corp.Inventors: Jacob J. Guth, Samual A. Vona, Jr., John S. Thomaides, Paul M. Petersen, Carmine Iovine
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Patent number: 6291683Abstract: Compounds useful for alleviating symptoms of depression are provided which have the following formula: wherein: R1 is hydrogen, lower alkyl or aryl; R2 is hydrogen, lower alkyl, phenyl or substituted phenyl; X and Y are each, independently, hydrogen, lower alkyl, lower alkoxy, or halogen, or together combine with the carbon atoms to which they are attached to complete a cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyranyl, pyridinyl, dihydrofuranyl, furanyl, dioxanyl, oxazolyl or isoxazolyl group; Z is hydrogen, halogen or lower alkoxy; with the proviso that when X, Y or Z represent lower alkoxy, they are not present at the ortho position; W is hydrogen, halogen, lower alkyl, cyano or a trifluoromethyl group; and n is 2-5; or pharmaceutically acceptable salts thereof.Type: GrantFiled: June 13, 2000Date of Patent: September 18, 2001Assignee: American Home Products CorpInventors: Richard E. Mewshaw, Dahui Zhou
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Publication number: 20010012851Abstract: Nitric oxide releasing oxindole prodrugs are described which are useful in methods of treating or preventing pain, inflammation, fever, or gastrointestinal lesions in a patient in need of such treatment, or of modifying an inflammatory disease or condition by favorably affecting the outcome thereof in said patient, wherein there is administered to said patient a therapeutically effective amount of a compound of Formula (I): 1Type: ApplicationFiled: July 29, 1999Publication date: August 9, 2001Inventors: KRISTIN M. LUNDY, MICHAEL T. CLARK