Nitrogen Attached To The Acid Group Directly Or Indirectly By Acyclic Nonionic Bonding (e.g., N-hydroxy Ureas, Dihydroxamic Acids, Etc.) Patents (Class 562/623)
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Patent number: 6444704Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.Type: GrantFiled: August 17, 2000Date of Patent: September 3, 2002Assignee: American Home Products CorporationInventors: Aranapakam Mudumbai Venkatesan, Janniee Lea Baker
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Patent number: 6433223Abstract: A silver halide photographic material is described, which contains the compound represented by the following formula (I): wherein R1 represents a substituted or unsubstituted alkylene group having from 1 to 5 carbon atoms; X represents a water-soluble group; and R represents a substituted or unsubstituted alkyl group having the sum total of from 14 to 40 carbon atoms, an alkenyl group, an aryl group, an alkoxyl group, —NR3R4 (R3 and R4 each independently represents an alkyl group having from I to 40 carbon atoms, a hydrogen atom, or an aryl group), a bicycloalkyl group, a bicycloalkenyl group, a cycloalkyl group, a cycloalkenyl group or a heterocyclic group, provided that when X represents a quaternary ammonium salt structure, R2 does not represent an alkyl group having from 14 to 17 carbon atoms.Type: GrantFiled: February 25, 2000Date of Patent: August 13, 2002Assignee: Fuji Photo Film Co., Ltd.Inventors: Hisashi Mikoshiba, Mamoru Sakurazawa, Masakazu Morigaki
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Publication number: 20020086890Abstract: Compounds of the formula: 1Type: ApplicationFiled: December 21, 2001Publication date: July 4, 2002Applicant: American Cyanamid CompanyInventors: Jeremy I. Levin, Aranapakam M. Venkatesan, James M. Chen, Arie Zask, Vincent P. Sandanayaka, Mila T. Du, Jannie L. Baker
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Patent number: 6414029Abstract: Monohydroxamate vanadium complexes of the formula (1): R—CO—NHOH.X, wherein R is a residue selected from: (i) H2N—CH(COY)—(CH2)n—, wherein n is 1, 2 or 3, and Y is OH or NH2; (ii) H2N—CH2—S—CH2—; and (iii) pyridyl, piperidyl or tetrahydroisoquinolinyl; and X is a vanadium compound selected from a vanadyl (VO2+), metavanadate (VO3−)or vanadate (VO43−)) salt, are useful for inducing normoglycemia and/or reducing blood glucose levels in diabetic patients.Type: GrantFiled: May 18, 2000Date of Patent: July 2, 2002Assignee: Yeda Research and Development Co. Ltd.Inventors: Yoram Shechter, Matityahu Fridkin, Itzhak Goldwasher, Eytan Gershonov
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Publication number: 20020076377Abstract: New types of hydroxamic acid-based bifunctional chelators are provided. These chelators are designed to chelate metal ions that can be detected either by their paramagnetic or radioactive properties. Conjugation with peptides or protein can be achieved by the presence of a linker moiety in the molecular structure of these chelators.Type: ApplicationFiled: December 18, 2000Publication date: June 20, 2002Inventors: Richard J. Flanagan, Jean-Marc Dufour
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Patent number: 6399776Abstract: This invention relates to novel processes for preparing the pharmaceutically active compound 5-(3-[(2S)-exo-bicyclo[2.2.1]hept-2-yloxy]-4-methoxyphenyl)-3,4,5,6-tetrahydropyrimidin-2(1H)-one and its corresponding 2R enantiomer and for preparing certain intermediates used in the synthesis of these compounds. It also relates to novel intermediates used in the synthesis of such pharmaceutically active compounds and to other novel compounds that are related to such intermediates.Type: GrantFiled: June 11, 2001Date of Patent: June 4, 2002Assignee: Pfizer INCInventors: Thomas G. LaCour, Charles William Murtiashaw, III
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Publication number: 20020055543Abstract: Compounds' of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, AA and Y are as defined herein, inhibit phosphodiesterase type IV or inhibit the production of tumor necrosis factor, and therefore are useful in the treatment of certain conditions and diseases including asthma, arthritis, and sepsis.Type: ApplicationFiled: January 25, 2001Publication date: May 9, 2002Inventor: Edward F. Kleinman
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Publication number: 20020038045Abstract: Novel hydroxamic acid compounds, e.g.Type: ApplicationFiled: October 9, 2001Publication date: March 28, 2002Inventors: Georg Kottirsch, Ulf Neumann
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Patent number: 6350907Abstract: Compounds of formula (I): or pharmaceutically acceptable salts thereof, or solvates of either entity, wherein the substituents have the values described herein, are useful as matrix metalloprotease (MMP) inhibitorsType: GrantFiled: April 11, 2000Date of Patent: February 26, 2002Assignee: Pfizer IncInventors: Michael Jonathan Fray, Roger Peter Dickinson, Kevin Neil Dack
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Publication number: 20020016368Abstract: Prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis.Type: ApplicationFiled: June 29, 2001Publication date: February 7, 2002Inventors: Kimberly O. Cameron, Hua Z. Ke, Bruce A. Lefker, Robert L. Rosati, David D. Thompson
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Patent number: 6344457Abstract: The invention concerns compounds of general formula (X) in which Y represents in particular —CONHOH, R1 represents in particular a C1-C5 alkyl group, AA represents an amino acid, or an amino acid sequence, and R3 represents in particular a group of formula —NH—(CH2)2—SCH3. The invention also concerns the pharmaceutical compositions containing them, and the methods for obtaining them.Type: GrantFiled: December 17, 1999Date of Patent: February 5, 2002Assignee: Chiesi Farmaceutici S.p.A.Inventors: Christian Jeanpetit, Didier Prigent, Pierre-André Settembre, Marie-Michèle Trancart
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Patent number: 6342508Abstract: Matrix metalloproteinases (MMps) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.Type: GrantFiled: August 17, 2000Date of Patent: January 29, 2002Assignee: American Cyanamid CompanyInventors: Aranapakam Mudumbai Venkatesan, George Theodore Grosu, Jamie Marie Davis, Derek Cecil Cole
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Publication number: 20010046663Abstract: A method to determine whether a test compound modulates the activity of an enzyme that has a metallated active site, comprising:Type: ApplicationFiled: May 27, 1999Publication date: November 29, 2001Inventors: PAUL G. GROTHAUS PH.D, DANA E. DAVIS, SEAN O'MALLEY
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Patent number: 6310084Abstract: The present invention relates to therapeutically active hydroxamic acid, N-formyl-N-hydroxyamino and carboxylic acid derivatives, their preparation, and pharmaceutical compositions containing them. These compounds are useful in the inhibition of metalloproteases, such as stromelysin, gelatinase, matrilysin, and collagenase. These compounds are useful in the treatment of mammals having disease-states alleviated by the inhibition of such matrix metalloproteases.Type: GrantFiled: February 11, 2000Date of Patent: October 30, 2001Assignee: British Biotech Pharmaceuticals LimitedInventors: Raymond Paul Beckett, Fionna Mitchell Martin, Richard Simon Todd
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Patent number: 6294694Abstract: Peptoid compounds of Formula I and Formula II are disclosed The compounds are useful in the treatment of matrix metalloproteinase-mediated disorders.Type: GrantFiled: June 4, 1999Date of Patent: September 25, 2001Assignee: Wisconsin Alumni Research FoundationInventors: Donald T. Witiak, Paul J. Bertics, Yingsheng Zhang
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Patent number: 6291520Abstract: Certain novel hydroxamic acid derivatives having the structure inhibit the enzyme lipoxygenase. These compounds, and the pharmaceutically acceptable salts thereof, are useful in the treatment or alleviation of inflammatory diseases, allergic conditions and cardiovascular diseases in mammals and as the active ingredient in pharmaceutical compositions for treating such conditions.Type: GrantFiled: June 28, 1993Date of Patent: September 18, 2001Assignee: PfizerInventors: Takafumi Ikeda, Akiyoshi Kawai, Takashi Mano, Yoshiyuki Okumura, Rodney William Stevens
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Patent number: 6251913Abstract: Compounds of formula (I), wherein: n is 1 to 6; Het is a nitrogen containing ring fused to the benzene ring on two adjacent carbon atoms to form a bicyclic ring system which ring system may be optionally substituted; R1 is hydrogen, C1-8alkyl, C2-6alkenyl, C2-6alkyny, C3-8cycloalkyl, aryl, heteroaryl, heterocyclyl, arylC1-6alkyl, heteroarylC1-6alkyl, heterocyclylC1-6alkyl or C3-8cycloalkylC1-6alkyl; R2 is C1-6alkyl, C2-6alkenyl, arylC1-6alkyl, heteroarylC1-6alkyl or the side-chain of a naturally occurring amino acid; R3 is hydrogen, C1-6alkyl, C3-8cycloalkyl, C4-8cycloalkenyl, arylC1-6alkyl, heteroarylC1-6alkyl or heterocycylC1-6alkyl; R4 is hydrogen or C1-6alkyl; or R3 and R4 together with the nitrogen atom to which they are joined form a heterocyclic ring; wherein any group or ring, in R1-R4, is optionally substituted; and pharmaceutically acceptable salts and in vivo hydrolysable esters thereof, are described as inhibitors of the production of Tumor Necrosis Factor and/or one or more matrType: GrantFiled: September 24, 1999Date of Patent: June 26, 2001Assignees: Zeneca Limited, Zeneca Pharma S.A.Inventor: Thomas Geoffrey Colerick Bird
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Patent number: 6235790Abstract: Hydroxamic acid derivatives of the general formula (I), in which Z, G, Ar, E, A1 and A have the meanings given in the description, to a process for their preparation, and to their use as pesticides, particularly as fungicides.Type: GrantFiled: July 20, 1999Date of Patent: May 22, 2001Assignee: Bayer AktiengesellschaftInventors: Bernd-Wieland Krüger, Lutz Assmann, Herbert Gayer, Peter Gerdes, Ulrich Heinemann, Dietmar Kuhnt, Thomas Seitz, Bernd Gallenkamp, Ral Tiemann, Gerd Hänssler, Heinz-Wilhelm Dehne, Stefan Dutzmann
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Patent number: 6235753Abstract: Inhibitors of the Production of s-CD23 and the secretion of TNF are provided.Type: GrantFiled: January 21, 1999Date of Patent: May 22, 2001Assignee: SmithKline Beecham p.l.c.Inventors: Stuart Bailey, Andrew Faller, David Glynn Smith, Derek Richard Buckle
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Patent number: 6172057Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.Type: GrantFiled: February 19, 1998Date of Patent: January 9, 2001Assignee: American Cyanamid CompanyInventors: Aranapakam Mudumbai Venkatesan, George Theodore Grosu, Jamie Marie Davis, Baihua Hu, Derek Cecil Cole, Jannie Lea Baker, Marcy Pamela Jacobson, Matthew Robin O'Dell
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Patent number: 6172064Abstract: A family of compounds having the general structural formula where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof. Also described are methods for their preparation, pharmaceutical compositions including such compounds and their use in medicine.Type: GrantFiled: August 25, 1999Date of Patent: January 9, 2001Assignee: Glaxo Wellcome Inc.Inventors: Robert Carl Andrews, Marc Werner Andersen, David John Cowan, David Norman Deaton, Scott Howard Dickerson, David Harold Drewry, Michael David Gaul, Michael Joseph Luzzio, Brian Edward Marron, Michael Howard Rabinowitz
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Patent number: 6159983Abstract: A composition in unit dosage form for the inhibition, prevention or treatment of inflammatory bowel disease comprising an effective amount of a compound having the formula: ##STR1## and a pharmaceutically acceptable carrier therefor.Type: GrantFiled: September 18, 1998Date of Patent: December 12, 2000Assignee: University of FloridaInventor: Raymond J. Bergeron, Jr.
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Patent number: 6153793Abstract: There is disclosed a method for producing an N-alkyl-.alpha.-dialkylaminoacetohydroxamic acid compound represented by formula (2), which comprises reacting an .alpha.-dialkylaminoacetic acid ester compound represented by formula (1) with an N-alkylhydroxylamine, wherein the reaction is carried out in water and an ether-series organic solvent, ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4, which are the same or different, each represents an alkyl group. According to the method, it is possible to obtain the objective compound in a high yield with a short reaction time, with restrained formation of a by-product.Type: GrantFiled: July 14, 1999Date of Patent: November 28, 2000Assignee: Fuji Photo Film, Ltd.Inventors: Masaharu Kitamura, Daisuke Urazoe, Hideto Mori, Akio Satoh
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Patent number: 6147114Abstract: New compounds of the general formula (I) ##STR1## (wherein R.sup.1 is a hydrogen atom, or a hydroxyl, aryl (C.sub.1 -C.sub.6)alkylene or --A--SOn--B group (A is a (C.sub.1 -C.sub.6) alkylene group; B is a (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) acyl, aryl or heterocyclyl group; n is 0, 1 or 2), R.sup.2 is a hydrogen atom, or a (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) alkyloxy 10 or (C.sub.1 -C.sub.6) alkylthio group, R.sup.3 and R.sup.4 are identical or different, representing a hydrogen atom, or a (C.sub.1 -C.sub.6) alkyl, aryl or aryl(C.sub.1 -C.sub.6)alkylene group, R.sup.5 is a --Y--C or C group (Y is a (C.sub.1 -C.sub.6) alkylene group, an oxygen atom, an imino group or a (C.sub.1 -C.sub.6) alkyleneimino group, C is a sulfonic acid, phosphonic acid, amidino, (C.sub.1 -C.sub.6) acyl, acylimidoyl, diphosphonomethine or dicarboxymethine group), and R.sup.Type: GrantFiled: October 24, 1997Date of Patent: November 14, 2000Assignee: Fuji Yakuhin Kogyo Kabushiki KaishaInventors: Tetsunori Fujisawa, Shinjiro Odake, Yasuo Morita, Tomoko Hongo, Hajime Ito, Junko Yasuda, Eiko Suda, Katsuhiro Igeta, Tadanori Morikawa
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Patent number: 6143744Abstract: This invention relates to sulfamides of formula (I) ##STR1## that are inhibitors of metalloproteases, pharmaceutical compositions containing them, methods for their use and methods for preparing these compounds.Type: GrantFiled: August 5, 1999Date of Patent: November 7, 2000Assignees: Syntex (U.S.A.) Inc., Agouron Pharmaceuticals, Inc.Inventors: Chris Allen Broka, Jeffrey Allen Campbell, Arlindo Lucas Castelhano, Jian Jeffrey Chen, Robert Than Hendricks, Michael Joseph Melnick, Keith Adrian Murray Walker
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Patent number: 6121487Abstract: The present invention is relative to a chemical method of producing compounds of the general formula (I) ##STR1## starting from compounds of the general formula (II) and (III) ##STR2## under radical conditions. Products I are used as intermediates in the synthesis of bioactive substances.Type: GrantFiled: July 28, 1999Date of Patent: September 19, 2000Assignee: Degussa-Huls AktiengesellschaftInventors: Annegret Vogt, Hans-Josef Altenbach, Michael Kirschbaum, Michael-Gottfried Hahn, Mike Siegfried Paul Matthaus, Andreas Rainer Hermann
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Patent number: 6090852Abstract: Compounds of formula (I): ##STR1## where the substituents are as defined herein, and salts thereof, are matrix metalloprotease inhibitors.Type: GrantFiled: January 20, 1999Date of Patent: July 18, 2000Assignee: Pfizer IncInventors: Kevin Neil Dack, Gavin Alistair Whitlock
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Patent number: 6063816Abstract: A compound selected from those of formula (I): ##STR1## wherein: R.sub.1 represents optionally substituted alkyl, acyl, cycloalkyl, aryl, aminocarbonylalkyl, or heterocycle,R.sub.2 represents alkylene,R.sub.3 represents X or Y as defined in the description,R.sub.4 represents--either alkyl, cycloalkyl, aryl, arylalkyl, cycloalkylalkyl, heterocycloalkylene, or heterocycle when R.sub.3 represents Y,or biaryl, arylheteroaryl or heteroarylaryl, when R.sub.3 represents X or Y,their isomers and also pharmaceutically-acceptable acid or base addition salts thereof, and medicinal products containing the same which are useful as metalloprotease inhibitors in the treatment of cancers.Type: GrantFiled: August 9, 1999Date of Patent: May 16, 2000Assignee: Adir et CompagnieInventors: Stephen Hanessian, Ghanem Atassi, Gordon Tucker, Daniel-Henri Caignard, Pierre Renard
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Patent number: 6057369Abstract: This invention is directed to compounds of formula I: ##STR1## wherein the variables are as described herein. Compounds within the scope of the present invention possess useful properties, more particularly pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase.Type: GrantFiled: September 12, 1997Date of Patent: May 2, 2000Assignee: Rhone-Poulenc Rorer Pharmaceuticals Inc.Inventors: Robert D. Groneberg, Kent W. Neuenschwander, Stevan W. Djuric, Gerald M. McGeehan, Christopher J. Burns, Steven M. Condon, Matthew M. Morrissette, Joseph M. Salvino, Anthony C. Scotese, John W. Ullrich
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Patent number: 6028110Abstract: A pharmaceutical or veterinary composition comprising a compound of formula I ##STR1## wherein X is a --CO.sub.2 H group and R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 are as defined in the specification, or a salt, hydrate or solvate thereof, and a pharmaceutically or veterinarily acceptable excipient or carrier. A method of treatment of diseases or conditions mediated by MMPs in mammals, such as rheumatoid arthritis, osteoarthritis, periodontitis, gingivitis, corneal ulceration or tumour invasion by secondary means, by administering to the mammal an effective amount of the composition.Type: GrantFiled: November 22, 1996Date of Patent: February 22, 2000Assignee: British Biotech Pharmaceuticals Ltd.Inventors: Andrew Miller, Raymond Paul Beckett, Fionna Mitchell Martin, Mark Whittaker
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Patent number: 6022898Abstract: Compounds of general formula (II), wherein X is a hydroxamic or carboxylic acid group, Y is sulphonyl and R.sub.1 and R.sub.2 as defined in the claims are matrix metalloproteinase inhibitors.Type: GrantFiled: December 23, 1996Date of Patent: February 8, 2000Assignee: British Biotech Pharmaceuticals LimitedInventors: Andrew Miller, Mark Whittaker, Raymond Paul Beckett
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Patent number: 6022893Abstract: The present invention relates to:(i) hydroxamic acid derivative of the formula (I): ##STR1## wherein R.sup.1 is hydrogen, or C1-4 alkyl; R.sup.2 is hydrogen, C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl; E is --CONR.sup.3 --, in which R.sup.3 is hydrogen, C1-4 alkyl, etc., --NR.sup.3 CO--, --CO--O--, --O--CO--etc.; A is hydrogen, C1-8 alkyl, C3-7 cycloalkyl, or Ar; J is bond, C2-4 alkylene etc.; G is --(CH.sub.2).sub.m --, in which m is 2, 3 or 4, or ##STR2## in which R.sup.6 and R.sup.7 is hydrogen, C1-8 alkyl etc.; and non-toxic salts thereof,ii) processes for the preparation thereof, andiii) pharmaceutical agents containing them.Type: GrantFiled: August 7, 1996Date of Patent: February 8, 2000Assignee: ONO Pharmaceutical Co., Ltd.Inventors: Katsuhito Sakaki, Hidekazu Kanazawa, Tsuneyuki Sugiura, Tohru Miyazaki, Hiroyukii Ohno
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Patent number: 6017889Abstract: Matrix metalloproteinase inhibiting compounds of formula (I), wherein X is a --CO.sub.2 H or --CONHOH group; and one of the groups proximate to the amide bonds is a steric bulky group, showing enhanced oral absorption.Type: GrantFiled: December 23, 1998Date of Patent: January 25, 2000Assignee: British Biotech Pharmaceuticals LimitedInventors: Raymond Paul Beckett, Mark Whittaker, Andrew Miller
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Patent number: 6008257Abstract: Hydroxamic derivatives of the formula (I): ##STR1## in which A represents hydrogen or a grouping which can be readily eliminated;A.sup.1 represents hydrogen or alkyl;Ar represents optionally substituted arylene or heteroarylene;E represents a 1-alkene-1,1-diyl grouping which contains a radical R.sup.1 in the 2-position, or represents a 2-aza-1-alkene-1,1-diyl grouping which contains a radical R.sup.2 in the 2-position, or represents an optionally substituted imino grouping ("azamethylone", N--R.sup.3);G represents a bridge member as defined herein; andZ represents in each case optionally substituted alkyl, alkenyl, alkinyl, cycloalkyl, aryl or heterocyclyl;are useful as fungicides. Also disclosed is a process for preparing the compounds of formula (I).Type: GrantFiled: August 21, 1997Date of Patent: December 28, 1999Assignee: Bayer AktiengesellschaftInventors: Bernd-Wieland Kruger, Lutz Assmann, Herbert Gayer, Peter Gerdes, Ulrich Heinemann, Dietmar Kuhnt, Thomas Seitz, Bernd Gallenkamp, Ralf Tiemann, Gerd Hanssler, Heinz-Wilhelm Dehne, Stefan Dutzmann
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Patent number: 5985911Abstract: C-terminal compounds of formula ##STR1## are potent inhibitors of matrix metalloproteinase and are useful in the treatment of diseases in which matrix metalloproteinase play a role. Also disclosed are matrix metalloproteinase inhibiting compositions and a method of inhibiting matrix metalloproteinase in a mammal.Type: GrantFiled: December 17, 1997Date of Patent: November 16, 1999Assignee: Abbott LaboratoriesInventors: Steven K. Davidsen, Alan S. Florjancic, George S. Sheppard, Jamie R. Giesler, Lianhong Xu, Yan Guo, Michael L. Curtin, Michael R. Michaelides, Carol K. Wada, James H. Holms
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Patent number: 5985900Abstract: Compounds of the formula I: ##STR1## wherein Y is O or S, Ar is an aryl group or a heteroaryl group, R is H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or --C(O)R.sub.1, wherein R.sub.1 is hydrogen, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or NR.sub.2 R.sub.3, wherein R.sub.2 and R.sub.3 independently are hydrogen, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, and X is --NH--OH or --OH. Pharmaceutically acceptable prodrugs, salts and solvates of these compounds. Methods of inhibiting the activity of metalloproteinases by administering a compound of the formula I or a prodrug, salt of solvate thereof. Pharmaceutical compositions comprising an effective amount of these compounds, prodrugs, salts, and solvates.Type: GrantFiled: March 30, 1998Date of Patent: November 16, 1999Assignee: Agouron Pharmaceuticals, Inc.Inventors: Steven L. Bender, Melwyn A. Abreo
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Patent number: 5917090Abstract: The invention is directed to therapeutically active hydroxamic acid derivatives of formula (I): ##STR1## wherein the substituents are as defined in the specification. These therapeutically active hydroxamic acid derivatives have high intrinsic activity against a broad spectrum of matrix metalloproteinases (MMPs), good oral bioavailability, and additionally inhibit tissue necrosis factor (TNF) production.Type: GrantFiled: December 19, 1997Date of Patent: June 29, 1999Assignee: British Biotech Pharmaceuticals Ltd.Inventors: Philip Huxley, Fionna Mitchell Martin, Andrew Miller, Zoe Marie Spavold
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Patent number: 5910609Abstract: Compounds of general Formula I: ##STR1## are presented which have collagenase inhibition activity and are useful in the management of disease involving tissue degradation and the promotion of wound healing. Representative diseases involving include arthropathy (particularly rheumatoid arthritis), inflammation, dermatological diseases, bone resorption disease and tumor invasion.Type: GrantFiled: April 5, 1995Date of Patent: June 8, 1999Assignee: British Biotech Pharmaceuticals LimitedInventors: Colin Campion, Alan Hornsby Davidson, Jonathan Philip Dickens, Michael John Crimmin
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Patent number: 5908851Abstract: Compounds of formula (I), ##STR1## wherein X is a --CO.sub.2 H or --CONHOH group; R.sub.4 is a group --CHR.sup.x R.sup.y wherein R.sup.x and R.sup.y independently represent optionally substituted phenyl or monocyclic heteroaryl rings, which optionally may be linked covalently to each other by a bond or by a C.sub.1 -C.sub.4 alkylene or C.sub.2 -C.sub.4 alkenylene bridge; and R.sub.1, R.sub.2, R.sub.3 and R.sub.5 are as defined in the specification are selective inhibitors of stromelysin-1 and matrilysin relative to human fibroblast collagenase and 72 KDa gelatinase.Type: GrantFiled: October 7, 1997Date of Patent: June 1, 1999Assignee: British Biotech Pharmaceuticals LimitedInventors: Raymond Paul Beckett, Andrew Miller, Zoe Marie Spavold, Mark Whittaker
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Patent number: 5902791Abstract: Matrix metalloproteinase inhibiting compounds of formula (I), wherein X is a --CO.sub.2 H or --CONHOH group; and one of the groups proximate to the amide bonds is a steric bulky group, showing enhanced oral absorption.Type: GrantFiled: July 22, 1996Date of Patent: May 11, 1999Assignee: British Biotech Pharmaceuticals LimitedInventors: Raymond Paul Beckett, Mark Whittaker, Andrew Miller
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Patent number: 5892112Abstract: Synthetic mammalian matrix metalloprotease inhibitors are disclosed that are useful for treating or preventing diseases wherein said diseases are caused by unwanted mammalian matrix metalloprotease activity and include skin disorders, keratoconus, restenosis, rheumatoid arthritis, wounds, cancer, angiogenesis and shock.Type: GrantFiled: January 21, 1994Date of Patent: April 6, 1999Assignees: Glycomed Incorporated, The University of FloridaInventors: Daniel E. Levy, Damian Grobelny, Cho Tang, Kevin R. Holme, Richard E. Galardy, Gregory S. Schultz, Asaad Nematalia, John H. Musser
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Patent number: 5863946Abstract: Compounds having the formula ##STR1## or a pharmaceutically acceptable salt thereof wherein Y is selected from halogen, alkyl, and haloalkyl; n is 0, 1, 2, or 3; X is absent or is alkylene; A is absent or is selected from optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted cycloalkylene wherein one or two of the carbon atoms is replaced with one or two heteroatoms independently selected from O, S, and N, optionally substituted alkenylene, and ##STR2## or R.sup.2 and A together define a saturated 5- to 8-membered optionally substituted carbocyclic or heterocyclic ring to which the group Z is attached; Z is selected from (a) hydrogen, (b) COM wherein M is selected from the group consisting of --OR.sup.5, a pharmaceutically acceptable cation, --NR.sup.7 R.sup.8, and a pharmaceutically acceptable, metabolically cleavable group, (c) --OR.sup.3, (d) tetrazolyl, (e) --CH(OR.sup.3)--CH.sub.2 OR.sup.9, (f) --CH(OR.sup.3)--CH.sub.2 --CH.sub.2 OR.sup.9, (g) --CH(OR.sup.Type: GrantFiled: June 6, 1996Date of Patent: January 26, 1999Assignee: Abbott LaboratoriesInventors: Clint D. W. Brooks, Richard A. Craig, Teodozyj Kolasa, Andrew O. Stewart
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Patent number: 5863949Abstract: A compound of formula (I), wherein n, X, R.sup.3, R.sup.4 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, restenosis, periodontal disease, epidermolysis bullosa, scleritis and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of TNF.Type: GrantFiled: August 4, 1997Date of Patent: January 26, 1999Assignee: Pfizer IncInventors: Ralph P. Robinson, James P. Rizzi
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Patent number: 5859061Abstract: The present invention provides a compound of formula I ##STR1## or pharmaceutically acceptable salts thereof wherein R.sup.1 and R.sup.2 are the same or different and are C.sub.1-10 alkyl, phenyl, hetero-aryl, or phenyl substituted with C.sub.1-4 alkyl, OR.sup.3, NHR.sup.3, CONHR.sup.3, NHCOR.sup.3, or halo; wherein R.sup.3 is H, or C.sub.1-4 alkyl; and n is 1, 2, 3, 4, 5, or 6. The compounds are inhibitors of matrix metalloproteinases involved in tissue degradation.Type: GrantFiled: January 9, 1998Date of Patent: January 12, 1999Assignee: Pharmacia & Upjohn CompanyInventors: Eric Jon Jacobsen, Louis L. Skaletzky
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Patent number: 5849951Abstract: A method for the preparation of a compound of formula (I) ##STR1## wherein X is hydrogen; Y is (i) a group --CO.sub.2 R.sub.5 wherein R.sub.5 is a carboxyl protecting group or (ii) a group --CONR.sub.6 OR.sub.7 wherein R.sub.6 is an amino protecting group and R.sub.7 is a hydroxyl protecting group; and S.sub.1, S.sub.2, S.sub.3 and S.sub.4 each represent covalently bound moieties which are substantially non-reactive with the reaction components (II), (III), or (IV) defined below, which method comprises causing the co-condensation in a liquid organic medium of a carboxylic acid reaction component of formula (II); an aldehyde of formula (IIIA); ammonia; and an isonitrile reaction component of formula (IV): ##STR2## wherein Y, S.sub.1, S.sub.2, S.sub.3 and S.sub.4 are as defined with respect to formula (I).Type: GrantFiled: August 29, 1997Date of Patent: December 15, 1998Assignee: British Biotech Pharmaceuticals LimitedInventors: Christopher David Floyd, Mark Whittaker
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Patent number: 5840974Abstract: Compound of formula (I) ##STR1## wherein Ar represents an optionally substituted phenyl or heteroaryl group, m is 1 or 2, n is 0, 1, 2, 3 or 4, X represents --COOH or --CONHOH and R.sub.1, R.sub.3 and Y are as defined in the specification,are inhibitors of metalloproteinases involved in tissue degradation.Type: GrantFiled: September 8, 1997Date of Patent: November 24, 1998Assignee: Britisch Biotech Pharmaceuticals, Ltd.Inventors: Mark Whittaker, Raymond Paul Beckett, Zoe Marie Spavold, Fionna Mitchell Martin
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Patent number: 5840939Abstract: Compounds of formula (I), wherein X is a --CO.sub.2 H or --CONHOH group; ##STR1## R.sub.4 is a group --CHR.sup.x R.sup.y wherein R.sup.x and R.sup.y independently represent optionally substituted phenyl or monocyclic heteroaryl rings, which optionally may be linked covalently to each other by a bond or by a C.sub.1 -C.sub.4 alkylene or C.sub.2 -C.sub.4 alkenylene bridge; and R.sub.1, R.sub.2, R.sub.3 and R.sub.5 as defined in the specification are selective inhibitors of stromelysin-1 and matrilysin relative to human fibroblast collagenase and 72 KDa gelatinase.Type: GrantFiled: October 7, 1997Date of Patent: November 24, 1998Assignee: British Biotech Pharmaceuticals, Ltd.Inventors: Raymond Paul Beckett, Andrew Miller, Zoe Marie Spavold, Mark Whittaker
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Patent number: 5821262Abstract: A compound of formula (I): ##STR1## wherein: R.sup.1 represents a (C.sub.1 -C.sub.6)alkyl, phenyl, substituted phenyl, or heterocyclyl group; R.sup.2 represents a (C.sub.1 -C.sub.6)alkyl group; R.sup.3 represents:(I) the side chain of arginine, lysine, tryptophan, histidine, serine, threonine, or cysteine, in which any polar amino, hydroxy, mercapto, guanidyl, imidazolyl or indolyl group is rendered substantially non-polar by substitution at the polar N-, O- or S-atom; or(ii) the side chain of aspartic or glutamic acid, in which side chain the carboxylic acid group is amidated;R.sup.4 represents hydrogen or a (C.sub.1 -C.sub.6)alkyl or phenyl (C.sub.1 -C.sub.6)alkyl group; R.sup.5 represents hydrogen or and n is 0, 1 or 2; or substituted phenyl groups; or a salt solvate or hydrate thereof. Compositions containing compound (I) and methods for treatment of diseases or conditions mediated by TNF or MMPs in mammals.Type: GrantFiled: October 28, 1996Date of Patent: October 13, 1998Assignee: British Biotech Pharmaceuticals LimitedInventors: Michael John Crimmin, Raymond Paul Beckett
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Patent number: 5804593Abstract: A compound of formula I or pharmaceutical acceptable salts thereof, ##STR1## wherein R.sub.1 is isopropyl, 2-methylbut-2yl, phenyl, benzyl, or 1H-indol-3ylmethyl; R.sub.2 is n-octyl, phenyl, or phenyl substituted with methoxy, fluoro, or bromo, are matrix metalloproteinase inhibitors.Type: GrantFiled: October 20, 1997Date of Patent: September 8, 1998Assignee: Pharmacia & Upjohn CompanyInventors: Martha A. Warpehoski, Mark Allen Mitchell, Eric Jon Jacobsen
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Patent number: 5798383Abstract: The prevent invention provides a compound of formula (I): ##STR1## wherein Ar is (a) phenyl, naphthyl and biphenyl, each optionally substituted with C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.2-4 alkoxyalkoxy, C.sub.1-4 alkylthio, hydroxy, halo, cyano, amino, C.sub.1-4 alkylamino, di (C.sub.2-8) alkylamino, C.sub.2-6 alkanoylamino, carboxy, C.sub.2-6 alkoxycarbonyl, or optionally substituted phenyl, phenoxy, phenylthio or phenylsulfinyl or (b) furyl, benzo?b!furyl, thienyl, benzo?b!thienyl, pyridyl or quinolyl, each optionally substituted with C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, halo, C.sub.1-4 alkoxy, optionally-substituted phneyl, phenoxy or phenylthio, X is C.sub.1 -C.sub.4 alkylene, C.sub.2 -C.sub.4 alkenylene, --(CHR.sup.1).sub.m --Q.sup.1 --(CHR.sup.2).sub.n --, --O--(CHR.sup.1).sub.j --Q.sup.2 -- and --(CHR.sup.1)--O--N.dbd. in which the N.dbd. moiety is attached to the cycloalkene ring; and in which Q.sup.1 is O, S, SO, SO.sub.2, NR.Type: GrantFiled: May 8, 1997Date of Patent: August 25, 1998Assignee: Pfizer Inc.Inventors: Akiyoshi Kawai, Makoto Kawai, Rodney W. Stevens