Halogen Attached Directly Or Indirectly To The Hetero Ring By Nonionic Bonding Patents (Class 549/73)
  • Patent number: 8642786
    Abstract: To provide a novel process for producing a 2-aryl-3-hydroxy-4-substituted carbonyl thiophene compound or an intermediate thereof useful as an intermediate for production of medicines and agricultural chemicals. A 2-aryl acetate compound represented by the formula (1): wherein R1 is an aryl group or the like, R4 is a C1-3 alkyl group or the like, and X is a leaving group, is reacted with a thioacetic acid compound to form a thioacetyl compound (3), the thioacetyl compound (3) is reacted with a vinyl ketone compound to form a ?-ketosulfide compound (5), which is cyclized under basic conditions to form a dihydrothiophene compound (6), and the dihydrothiophene compound (6) is oxidized by using an oxidizing agent to produce a 2-aryl-3-hydroxy-4-substituted carbonyl thiophene compound (7).
    Type: Grant
    Filed: March 15, 2013
    Date of Patent: February 4, 2014
    Assignee: Nissan Chemical Industries, Ltd.
    Inventors: Kazufumi Yanagihara, Shingo Umezawa, Katsuaki Miyaji
  • Publication number: 20130144071
    Abstract: A method of the present invention, for producing an iodizing agent, includes the step of electrolyzing iodine molecules in a solution by using an acid as a supporting electrolyte. This realizes (i) a method of producing an iodine cation suitable for use as an iodizing agent that does not require a sophisticated separation operation after iodizing reaction is completed, and (ii) an electrolyte used in the method. Further, a method of the present invention, for producing an aromatic iodine compound, includes the step of causing an iodizing agent, and an aromatic compound whose nucleus has one or more substituent groups and two or more hydrogen atoms, to react with each other under the presence of a certain ether compound. This realizes such a method of producing an aromatic iodine compound that position selectivity in iodizing reaction of an aromatic compound is improved.
    Type: Application
    Filed: January 30, 2013
    Publication date: June 6, 2013
    Applicants: NIPPOH CHEMICALS CO., LTD., JAPAN SCIENCE AND TECHNOLOGY AGENCY
    Inventors: Japan Science and Technology Agency, Nippoh Chemicals Co., Ltd.
  • Publication number: 20110049427
    Abstract: The present invention relates to thiophene derivatives, to processes and intermediates for the preparation thereof, to the use thereof for optical, electro-optical and electronic purposes, in particular in liquid-crystal (LC) media and LC displays, and to LC media and LC displays comprising same.
    Type: Application
    Filed: March 30, 2009
    Publication date: March 3, 2011
    Applicant: MERCK PATENT GESELLSCHAFT
    Inventors: Axel Jansen, Detlef Pauluth, Harald Hirschmann, Markus Czanta
  • Publication number: 20100278733
    Abstract: There is provided a composition comprising a compound represented by general formula (I), wherein Rl represents a 5-iodothiophen-2-yl group or the like, and R2 represents a 4-dimethylaminophenyl group or the like. This composition is useful for diagnosis of an amyloid-related disease such as Alzheimer's disease because the compound has high binding specificity to amyloid ? protein, high permeability through the blood-brain barrier, and a property of being rapidly eliminated from sites other than senile plaques in the brain.
    Type: Application
    Filed: May 22, 2007
    Publication date: November 4, 2010
    Inventors: Morio Nakayama, Mamoru Haratake, Masahiro Ono
  • Patent number: 7799825
    Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts and tautomers thereof. Compounds of the present invention are inhibitors of histone deacetylase (HDAC) and are useful for treating cellular proliferative diseases, including cancer. They are also useful for treating neurodegenerative diseases, mental retardation, 10 schizophrenia, inflammatory diseases, restenosis, immune disorders, diabetes, cardiovascular disorders and asthma.
    Type: Grant
    Filed: February 14, 2007
    Date of Patent: September 21, 2010
    Assignee: Istituto di Ricerche di Biologia Molecolare P. Angeletti SpA
    Inventors: Federica Ferrigno, Philip Jones, Ester Muraglia, Jesus Maria Ontoria Ontoria, Rita Scarpelli, Carsten Schultz-Fademrecht
  • Patent number: 7745483
    Abstract: Novel 2-halofuryl/thienyl-3-carboxamides of the formula (I) in which A, Hal, R, M and Z are as defined in the description, a plurality of processes for preparing these compounds and their use for controlling unwanted microorganisms, and also novel intermediates and their preparation.
    Type: Grant
    Filed: January 22, 2005
    Date of Patent: June 29, 2010
    Assignee: Bayer CropScience AG
    Inventors: Ralf Dunkel, Hans-Ludwig Elbe, Jörg Nico Greul, Benoit Hartmann, Peter Dahmen, Karl-Heinz Kuck, Ulrike Wachendorff-Neumann
  • Publication number: 20100075946
    Abstract: The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.
    Type: Application
    Filed: June 20, 2006
    Publication date: March 25, 2010
    Applicant: Actelion Pharmaceuticals Ltd.
    Inventors: Martin Bolli, David Lehmann, Boris Mathys, Claus Mueller, Jörg Velker
  • Publication number: 20100029745
    Abstract: The present invention relates to compounds derived from substituted 3-phenyl-1-(thien-2-yl)propan-1-ones, pharmaceutical compositions comprising them as well as their therapeutic applications, notably in the field of human and animal health.
    Type: Application
    Filed: December 28, 2007
    Publication date: February 4, 2010
    Inventor: Jean-Francois Delhomel
  • Publication number: 20090076101
    Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts and tautomers thereof. Compounds of the present invention are inhibitors of histone deacetylase (HDAC) and are useful for treating cellular proliferative diseases, including cancer. They are also useful for treating neurodegenerative diseases, mental retardation, 10 schizophrenia, inflammatory diseases, restenosis, immune disorders, diabetes, cardiovascular disorders and asthma.
    Type: Application
    Filed: February 14, 2007
    Publication date: March 19, 2009
    Inventors: Federica Ferrigno, Philip Jones, Ester Muraglia, Jesus Maria Ontoria Ontoria, Rita Scarpelli, Carsten Schultz-Fademrecht
  • Patent number: 7365094
    Abstract: The present invention relates to compounds of the general formula (II) and salts and physiologically functional derivatives thereof, for the use as a medicament.
    Type: Grant
    Filed: December 17, 2003
    Date of Patent: April 29, 2008
    Assignee: 4SC AG
    Inventors: Johann Leban, Stefan Tasler
  • Patent number: 7332518
    Abstract: The invention concerns novel carboxamides of formula (I) wherein A is (A1), (A2), (A3), (A4), (A5); Q is (Q1), (Q2), (Q3), (Q4), (Q5), (Q6); R1 is CH2 R2, CH2CH?CHR2, CH?C?CHR2 or COR3; R2 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, COOC1-C4alkyl, COOC3-C6alkenyl, COOC3-C6alkynyl or CN; R3 is C1-C6alkyl, C1-C6alkyl substituted by halogen, C1-C6alkoxy or C1-C6haloalkoxy; or is C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkoxy, C1-C6haloalkoxy; C3-C6alkenyloxy or C3-C6haloalkenyloxy; C3-C6haloalkenyloxy; C3-C6alkynyloxy or C3-C6haloalkynyloxy; R4 is methyl, CF2Cl, CF3, CF2H, CFH2, Cl or Br, R5 is methyl, CF3, CH2OCH3 or CH2OCF3; R6 is hydrogen, fluoro, CF3 or methyl; R7 is hydrogen, methyl or halogen; and Z is phenyl, halophenyl, C5-C7cycloalkyl, C5-C7cycloalkyl substituted by C1-C3alkyl, C1C3haloalkyl or halogen, or a group of the form —CHR8—CH2—CHR9R10 wherein R8, R9 and R10 are independently of each other C1-C3alkyl.
    Type: Grant
    Filed: January 24, 2002
    Date of Patent: February 19, 2008
    Assignee: Syngenta Crop Protection, Inc.
    Inventors: Harald Walter, Stephan Trah
  • Patent number: 7211679
    Abstract: Semiconductor devices are described that include a semiconductor layer that comprises a perfluoroether acyl oligothiophene compound, preferably an ?,?-bis-perfluoroether acyl oligothiophene compound. Additionally, methods of making semiconductor devices are described that include depositing a semiconductor layer that contains a perfluoroether acyl oligothiophene compound, preferably an ?,?-bis(2-perfluoroether acyl oligothiophene compound.
    Type: Grant
    Filed: March 9, 2005
    Date of Patent: May 1, 2007
    Assignee: 3M Innovative Properties Company
    Inventors: Christopher P. Gerlach, David A. Ender, Dennis E. Vogel
  • Patent number: 7034053
    Abstract: The present invention disclosed compounds of Formula I. The present invention also discloses beta-3 agonists of formula I and methods for treating beta-3 mediated diseases and condition using the compounds of formula I, in particular methods for treating diabetes or obesity.
    Type: Grant
    Filed: December 17, 2001
    Date of Patent: April 25, 2006
    Assignee: SmithKline Beecham Corporation
    Inventors: David N. Deaton, Barry George Shearer, David Edward Uehling
  • Patent number: 6835745
    Abstract: This invention provides estrogen receptor modulators of formula I, having the structure wherein, R1, R2, R3, X, and Y are as defined in the specification, or a pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: January 10, 2003
    Date of Patent: December 28, 2004
    Assignee: Wyeth
    Inventors: Richard D. Coghlan, William F. Fobare, Heather A. Harris, James C. Keith, Jr., Leo M. Albert
  • Patent number: 6747057
    Abstract: Compounds of formula I: [wherein: X represents —CH═CH—, —CH═CR—, —CR═CR—, —CO—, —O—, —NH—, —NR—, S—, —SO—, —SO2—, —CH═N—, —CR═N—, —CH═N(O)—, —CR═N(O)— or any other atom or group of atoms capable of forming a S— or 6-membered heterocyclic ring; Y1, Y2 and Y3 independently represent hydrogen or halogen; R1, R2 and R3 are independently represent hydrogen, halogen, hydrocarbyl (—R), hydroxyl (—OH), hydrocarbyloxy (—O—R), mercapto (—SH), hydrocarbylthio (—S—R), hydrocarbylsulfinyl (—SO—R), hydrocarbylsulfonyl (—SO2—R), nitro (—NO2), amino (—NH2), hydrocarbylamino (—NHR), bis(hydrocarbyl)amino (—NR2), hydrocarbylcarbonylamino (—NH—CO—R), cyano (—CN), carbamoyl (—CONH2), hy
    Type: Grant
    Filed: December 20, 2002
    Date of Patent: June 8, 2004
    Assignees: Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Matrid (UAM)
    Inventors: Santiago Conde Ruzafa, Ana Martinez Gil, Daniel Ignacio Perez Fernandez, Maria Concepcion Perez Martin, Francisco Jose Moreno Munoz, Francisco Wandosell Jurado
  • Patent number: 6627652
    Abstract: Process of treatment of mammals, including humans to treat diseases or conditions of the type which are normally treated with retinoid-like compounds is disclosed, with pharmaceutical compositions containing an active compound which is a selective agonist of the RXR retinoid receptor sites in preference to the RAR retinoid receptor sites. A compound is defined to be a selective agonist of the RXR receptor site if the compound is at least approximately ten times more effective as an agonist in the RXR receptor sites than in the RAR receptor sites.
    Type: Grant
    Filed: April 20, 1995
    Date of Patent: September 30, 2003
    Assignee: Allergan, Inc.
    Inventor: Roshantha A. S. Chandraratna
  • Patent number: 6566375
    Abstract: Compounds of this invention increase plasma levels of high density lipoprotein or HDL, the “good” cholesterol and as such may be useful for treating diseases such as atherosclerosis.
    Type: Grant
    Filed: April 26, 2001
    Date of Patent: May 20, 2003
    Assignee: Wyeth
    Inventor: Thomas J. Commons
  • Patent number: 6323214
    Abstract: The present invention relates to compounds of formulas (IA), (IB), and (IC): the preparation thereof, pharmaceutical formulations thereof, and their use in medicine as allosteric adenosine receptor modulators for uses including protection against hypoxia and ischemia induced injury and treatment of adenosine-sensitive cardiac arrhythmias.
    Type: Grant
    Filed: September 17, 1998
    Date of Patent: November 27, 2001
    Assignee: Medco Research, Inc
    Inventor: Pier Giovanni Baraldi
  • Patent number: 6313302
    Abstract: A compound of the following formula: and the salts thereof, wherein A is hydrogen, halo, or hydroxy; the broken line represents an optional double bond with proviso that if the broken line is a double bond, then A is absent; Ar1 is optionally substituted phenyl; Ar2 is aryl or heteroaryl selected from phenyl, napththyl, or pyridyl, the aryl or heteroaryl being optionally substituted; R1 is hydrogen, hydroxy, or C1-C4 alkyl; and R2 and R3 are independently selected from optionally substituted C1-C7 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, or R2 and R3, together with the nitrogen atom to which they are attached, form an optionally substituted pyrrolidine. These compounds are useful as kappa agonists.
    Type: Grant
    Filed: January 26, 2001
    Date of Patent: November 6, 2001
    Assignee: Pfizer Inc.
    Inventors: Fumitaka Ito, Hiroshi Kondo
  • Patent number: 6248773
    Abstract: The invention relates to the use of cyclopentane heptan(ene)oic acid, 2-heteroarylalk(en)yl derivatives as ocular hypotensives.
    Type: Grant
    Filed: August 22, 2000
    Date of Patent: June 19, 2001
    Assignee: Allergan Sales, Inc.
    Inventor: Robert M. Burk
  • Patent number: 6080861
    Abstract: A compound is disclosed having the formula: ##STR1## The compound is useful as an active ingredient in a herbicidal composition.
    Type: Grant
    Filed: November 3, 1998
    Date of Patent: June 27, 2000
    Assignee: American Cyanamid Company
    Inventors: Gary Mitchell Karp, Michael Edward Condon, Axel Kleemann
  • Patent number: 6025383
    Abstract: The invention relates to novel thiophene derivatives of the formula (I) ##STR1## in which X represents halogen, alkyl, alkoxy, alkylthio, halogenoalkyl, halogenoalkoxy, nitro or cyano, or two substituents X, together with the carbon atoms to which they are attached, form a saturated or unsaturated, optionally substituted ring,n represents a number from 1 to 3, andZ represents one of the groups ##STR2## in which A, B, D, G, Q.sup.1, Q.sup.2 and Q.sup.3 have the meaning given in the description, to processes for their preparation and to their use as pesticides and herbicides.
    Type: Grant
    Filed: June 3, 1998
    Date of Patent: February 15, 2000
    Assignee: Bayer Aktiengesellschaft
    Inventors: Reiner Fischer, Jacques Dumas, Thomas Bretschneider, Bernd Gallenkamp, Folker Lieb, Konrad Wernthaler, Christoph Erdelen, Ulrike Wachendorff-Neumann, Norbert Mencke, Andreas Turberg
  • Patent number: 6013664
    Abstract: Novel microbicidal compositions based on thiophene-2-carboxylic acid derivatives, some of which are known, of the formula in whichR.sup.1, R.sup.2 and n have the meanings given in the description, and the use of these substances for controlling undesired microorganisms.Novel thiophene-2-carboxylic acid derivatives of the formula ##STR1## in which R.sup.1, R.sup.2 and p have the meanings given in the description, and a process for the preparation of the substances of the formula (I-a).
    Type: Grant
    Filed: May 26, 1999
    Date of Patent: January 11, 2000
    Assignee: Bayer Aktiengesellschaft
    Inventors: Reiner Fischer, Norbert Lui, Stefan Dutzmann, Gerd Hanssler
  • Patent number: 6004948
    Abstract: Compounds of the formula (I) in which A is oxygen, sulphur or NH; B is a group of the formula (IIa) or (IIb); and the other variables have the meaning given in claim 1, may be used as inhibitors of the enzyme cyclooxygenase II ##STR1##
    Type: Grant
    Filed: September 3, 1998
    Date of Patent: December 21, 1999
    Assignee: Nycomed Austria GmbH
    Inventors: Heinz Blaschke, Peter Kremminger, Michael Hartmann, Harald Fellier, Jorg Berg, Thomas Christoph, Franz Rovenszky, Dagmar Stimmeder
  • Patent number: 6005113
    Abstract: The invention relates to fluorescent dyes that are substituted or unsubstituted derivatives of 1-(isoindolyl)methylene-isoindole that are bound through both isoindole nitrogens to a boron difluoride moiety, forming a fluorescent dibenzopyrrometheneboron difluoride compound ##STR1## that is further substituted by bathochromic substituents that are aryl or heteroaryl moieties further substituted by an additional aryl or heteroaryl, that is itself optionally further substituted by an additional aryl or heteroaryl. These aryl and heteroaryl groups are separated by a covalent bond, or by an ethenyl, butadienyl or hexatrienyl linkage. The dyes of the invention are particularly useful as labels for carriers, particularly polymeric microparticles. The resulting microparticles have a long-wavelength fluorescence emission, and possess utility for tracing flow in biological systems, particularly in tracing blood flow.
    Type: Grant
    Filed: May 14, 1997
    Date of Patent: December 21, 1999
    Assignee: Molecular Probes, Inc.
    Inventors: Yexin Wu, Dieter H. Klaubert, Hee Chol Kang, Yu-Zhong Zhang
  • Patent number: 5856323
    Abstract: 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 2,4-diaryl tetrahydrofurans, 2,4-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes, 2,4-diaryl pyrrolidines, and 2,5-diaryl pyrrolidines are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i. e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase.A method to treat disorders mediated by PAF or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: January 5, 1999
    Assignee: CytoMed, Inc.
    Inventors: Xiong Cai, Sajjat Hussoin, San-Bao Hwang, David Killian, T. Y. Shen
  • Patent number: 5834498
    Abstract: The invention relates to the use of derivatives of F-type prostaglandins as ocular hypotensives. The PGF derivatives used in accordance with the invention are represented by the following formula I: ##STR1## wherein wavy line attachments indicate either the alpha (.alpha.) or beta (.beta.) configuration; hatched segments indicate .alpha. configuration, solid triangles are used to indicate .beta. configuration, dashed bonds represent a double bond, or a single bond, R is a substituted heteroaryl radical, R.sup.1 is hydrogen or a lower alkyl radical having up to six carbon atoms, X is selected from the group consisting of --OR.sup.1 and --N(R.sup.1).sub.2, Y is .dbd.O or represents 2 hydrogen radicals. Certain of the compounds represented by Formula I comprise another aspect of the present invention.
    Type: Grant
    Filed: October 7, 1996
    Date of Patent: November 10, 1998
    Assignee: Allergan
    Inventor: Robert M. Burk
  • Patent number: 5789437
    Abstract: New microbicidal compositions based on dibromo-thiophene-carboxylic acid derivatives which are known in some cases, of the formula ##STR1## in which R represents the groups --XR.sup.1, --NR.sup.2 R.sup.3, --NR.sup.4 OR.sup.5 or --NR.sup.4 --N(R.sup.5).sub.2, whereX represents oxygen or sulphur andR.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the meanings indicated in the description, and the use of these substances for controlling undesired microorganisms.New dibromo-thiophene-carboxylic acid derivatives of the formula ##STR2## in which R.sup.9 represents the groups --SR.sup.1, --OR.sup.10, ##STR3## in which R.sup.1, R.sup.4, R.sup.5, R.sup.10, R.sup.11, R.sup.12 and R.sup.13 have the meaning indicated in the description, and processes for the preparation of the substances of the formula (I-A).
    Type: Grant
    Filed: October 4, 1996
    Date of Patent: August 4, 1998
    Assignee: Bayer Aktiengesellschaft
    Inventors: Hans-Ludwig Elbe, Lutz Assmann, Ralf Tiemann, Uta Ecker, Gerd Hanssler, Heinz-Wilhelm Dehne
  • Patent number: 5747518
    Abstract: The substituted thiophene derivative of the invention which is represented by the general formula (1) has a broad disease spectrum for a pathogenic fungus of various crops, exhibits an excellent controlling effect on disease such as gray mold, powdery mildew and rust in particular, and is also effective for a resistant fungus of conventional fungicides which has become a serious problem, and consequently is useful for an agricultural and horticultural fungicide.
    Type: Grant
    Filed: April 3, 1996
    Date of Patent: May 5, 1998
    Assignee: Mitsui Toatsu Chemicals, Inc.
    Inventors: Yukihiro Yoshikawa, Kanji Tomiya, Hiroyuki Katsuta, Hideo Kawashima, Osamu Takahashi, Shunichi Inami, Yuji Yanase, Junro Kishi, Hitoshi Shimotori, Naofumi Tomura
  • Patent number: 5739140
    Abstract: Novel compounds of Formula I and methods of making and using the compounds which are useful as fungicides, particularly in the agricultural field: ##STR1## wherein C.sub.1 and C.sub.2 are carbon atoms which are part of an aromatic ring; W is alkoxyimino, alkoxymethylene or alkylthiomethylene; R.sub.1 is independently selected from the group consisting of halogen, cyano, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, wherein the alkyl or alkoxy are optionally substituted by halogen, and p is 0, 1, or 2; Z is --CH.sub.2 --, --CH(OH)--, --CO--, --O--, --S--, NR.sub.2 wherein R.sub.2 is hydrogen or a lower aliphatic group, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, ##STR2## --CH.sub.2 O--, --CH.sub.2 S--, --CH.sub.2 S(O)--, --OCH.sub.2 --, --SCH.sub.2 --, --S(O)CH.sub.2 --, --CH.sub.2 ON.dbd.C(R.sub.3)-- or --CH.dbd.NB wherein B is --O--CO--, --N.dbd.CR.sub.3, or --CR.sub.3 R.sub.4 -- wherein R.sub.3 and R.sub.4 are independently hydrogen or C.sub.1 -C.sub.
    Type: Grant
    Filed: October 23, 1996
    Date of Patent: April 14, 1998
    Assignee: Monsanto Company
    Inventors: William P. Clinton, Jim I. McLoughlin, Anita E. Otal, John J. Parlow, Dennis P. Phillion, Ajit S. Shah
  • Patent number: 5650522
    Abstract: Process for the preparation of derivatives having general formula (I) ##STR1## wherein the meaning of R will be defined in the text, characterized by the reaction between a compound having formula ##STR2## wherein X is an halogen, and an alkaline salt of a methyl dialkylmalonate.
    Type: Grant
    Filed: June 14, 1996
    Date of Patent: July 22, 1997
    Assignee: Erregierre S.P.A.
    Inventors: Antonio Bonaldi, Massimo Ferrari, Egidio Molinari, Fabrizio Zinetti
  • Patent number: 5648486
    Abstract: 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 2,4-diaryl tetrahydrofurans, 2,4-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes, 2,4-diaryl pyrrolidines, and 2,5-diaryl pyrrolidines are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i.e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase.A method to treat disorders mediated by PAF or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
    Type: Grant
    Filed: May 12, 1993
    Date of Patent: July 15, 1997
    Assignee: CytoMed, Inc.
    Inventors: Xiong Cai, Sajjat Hussoin, San-Bao Hwang, David Killian, T. Y. Shen
  • Patent number: 5610319
    Abstract: The invention generally relates to compounds of the formula I, which are in equilibrium with their 4-hydroxy tautomers, and their pharmaceutically acceptable salts: ##STR1## where n is 0 to 2; A is S, CH.sub.2, O, NH or Se, and when n is 0, A is not CH.sub.2, and when n is 1, A is not CH.sub.2 or NH; X is a substituted or unsubstituted C.sub.1 -C.sub.3 alkyl, C.sub.2 -C.sub.3 alkenyl, C.sub.2 -C.sub.3 alkynyl or amino, or sulfur or oxygen; Ar is a substituted or unsubstituted monocyclic carbocycle or heterocycle, or fused or nonfused polycyclic carbocycle or heterocycle; and R.sub.1 and R.sub.2 are hydrogen or a moiety that forms together with the attached CO.sub.2 a readily hydrolyzable ester group. These compounds and their salts are useful as inhibitors of GARFT or as antiproliferative agents. The invention also pertains to pharmaceutical compositions and methods employing such Compounds as GARFT inhibitors or antiproliferative agents.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: March 11, 1997
    Assignee: Agouron Pharmaceuticals, Inc.
    Inventors: Michael D. Varney, William H. Romines, Cynthia L. Palmer
  • Patent number: 5608082
    Abstract: Compounds of the Formula I, which are in equilibrium with their 4-hydroxy tautomers and are in the form of diastereomeric mixtures, and their pharmaceutically acceptable salts are potent GARFT inhibitors: ##STR1## wherein A, Z, X, and R.sub.1 and R.sub.2 are defined in the specification. These compounds and their salts are useful as antiproliferative agents. The invention also pertains to pharmaceutical compositions and methods employing such compounds as GARFT inhibitors or antiproliferative agents. The invention also relates to compounds useful as intermediates for preparing such compounds, and to their synthesis.
    Type: Grant
    Filed: July 28, 1994
    Date of Patent: March 4, 1997
    Assignee: Agouron Pharmaceuticals, Inc.
    Inventors: Michael D. Varney, William H. Romines
  • Patent number: 5563250
    Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier.
    Type: Grant
    Filed: May 13, 1994
    Date of Patent: October 8, 1996
    Assignee: NeoRx Corporation
    Inventors: Mark D. Hylarides, Ananthachari Srinivasan, Jeffrey N. Fitzner, Vivekananda M. Vrudhula
  • Patent number: 5527955
    Abstract: The invention concerns a method for treating depression or senile dementia using a compound which acts selectively as an agonist of gamma aminobutyric acid (GABA) at GABA autoreceptors with the proviso that the compound is not fengabine and progabide.
    Type: Grant
    Filed: December 23, 1993
    Date of Patent: June 18, 1996
    Assignee: John Wyeth & Brother, Limited
    Inventors: Michael C. W. Minchin, John F. White
  • Patent number: 5480902
    Abstract: There are provided fungicidal thienyl- and furylpyrrole compounds of formula I ##STR1## Further provided are compositions and methods comprising those compounds for the protection of plants from fungal infestation and disease.
    Type: Grant
    Filed: August 31, 1993
    Date of Patent: January 2, 1996
    Assignee: American Cyanamid Company
    Inventors: Roger W. Addor, Joseph A. Furch, III, Laurelee A. Duncan
  • Patent number: 5470977
    Abstract: The present invention provides novel ring-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes, 3-aminochromanes, and 3-aminothiochromanes, including their corresponding sulfoxides and sulfones, which ring-substituted compounds exhibit agonist activity at the serotonin 1A receptor.
    Type: Grant
    Filed: March 14, 1995
    Date of Patent: November 28, 1995
    Assignee: Eli Lilly and Company
    Inventors: John M. Schaus, Craig S. Hoechstetter, Diane Huser, Charles J. Paget, Robert D. Titus
  • Patent number: 5463083
    Abstract: 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i,e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. Also disclosed is a method to treat disorders mediated by PAF and/or leukotrienes that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, to a patient in need of such therapy.
    Type: Grant
    Filed: January 6, 1994
    Date of Patent: October 31, 1995
    Assignee: Cytomed, Inc.
    Inventors: Tesfaye Biftu, Xiong Cai, Sajjet Hussion, Gurmit Grewal, T. Y. Shen
  • Patent number: 5455265
    Abstract: Process of treatment of mammals, including humans to treat diseases or conditions of the type which are normally treated with retinoid-like compounds is disclosed, with pharmaceutical compositions containing an active compound which is a selective agonist of the RXR retinoid receptor sites in preference to the RAR retinoid receptor sites. A compound is defined to be a selective agonist of the RXR receptor site if the compound is at least approximately ten times more effective as an agonist in the RXR receptor sites than in the RAR receptor sites.
    Type: Grant
    Filed: February 11, 1993
    Date of Patent: October 3, 1995
    Assignee: Allergan, Inc.
    Inventor: Roshantha A. S. Chandraratna
  • Patent number: 5434151
    Abstract: 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 2,4-diaryl tetrahydrofurans, 2,4-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes, 2,4-diaryl pyrrolidines, and 2,5-diaryl pyrrolidines are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i.e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase.A method to treat disorders mediated by PAF or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
    Type: Grant
    Filed: August 24, 1992
    Date of Patent: July 18, 1995
    Assignee: CytoMed, Inc.
    Inventors: Xiong Cai, Sajjat Hussoin, San-Bao Hwang, David Killian, T. Y. Shen
  • Patent number: 5424448
    Abstract: A process for synthesizing carbonic anhydrase inhibitors is disclosed.
    Type: Grant
    Filed: January 14, 1994
    Date of Patent: June 13, 1995
    Assignee: Alcon Laboratories, Inc.
    Inventors: William D. Dean, Paul W. Zinke, Steven J. Sproull, Michael E. Deason, Raymond E. Conrow, Anura P. Dantanarayana
  • Patent number: 5371240
    Abstract: 3-substituted thiophene compounds contaminating the analogous 2-substituted thiophene compounds, e.g. 3-acetylthiophene contaminating 2-acetyl thiophene, are removed by a selective electrophilic substitution process, e.g. bromination, followed by fractional distillation. It has been found that electrophilic substitution as exemplified by bromination is highly selective towards the 3-substituted thiophenes, yielding compounds of significantly higher molecular weights for separation purposes, to give high purity 2-substituted thiophene compounds.
    Type: Grant
    Filed: November 30, 1992
    Date of Patent: December 6, 1994
    Assignee: Torcan Chemical Ltd.
    Inventor: Clarke Slemon
  • Patent number: 5358938
    Abstract: 2,5-Diaryl tetrahydrofurans, 2,5-diaryl terahydrothiophenes, 2,4-diaryl tetrahydrofurans, 2,4-diaryl tetrahydrothiphenes, 1,3-diaryl cyclopentanes, 2,4-diaryl pyrrolidines, and 2,5-diaryl pyrrolidines are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i.e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase.A method to treat disorders mediated by PAF or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
    Type: Grant
    Filed: July 13, 1992
    Date of Patent: October 25, 1994
    Assignee: CytoMed, Inc.
    Inventors: Xiong Cai, Saijat Hussoin, San-Bao Hwang, David Killian, T. Y. Shen
  • Patent number: 5235068
    Abstract: Acylaromatic compounds ##STR1## (Q: aromatic compound residue; R: straight, branched or cyclic aliphatic group, aromatic group or araliphatic group) are prepared in high yield by a reaction, in the presence of a boron trifluoride complex catalyst, of an aromatic compound with ##STR2## (X: H, Cl, Br; Y: Cl, Br) or with RCOOH in the presence of (XYCHCO).sub.2 O.
    Type: Grant
    Filed: July 21, 1992
    Date of Patent: August 10, 1993
    Assignee: Sumitomo Chemical Company, Limited
    Inventors: Masayoshi Minai, Michitada Kondo, Yuji Ueda, Seiichi Kai, Takayuki Higashii
  • Patent number: 5216139
    Abstract: Thiopheneazo dyes of the formula ##STR1## where R.sup.1 is cyano, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenylazo, phenylsulfonyl, formyl or the radical ##STR2## where R.sup.7 and R.sup.8 are independently of the other cyano or C.sub.1 -C.sub.4 -alkoxycarbonyl,R.sup.2 is C.sub.1 -C.sub.4 -alkyl, phenyl, halogen, C.sub.1 -C.sub.4 -alkoxy or C.sub.1 -C.sub.4 -alkoxycarbonyl, or R.sup.1 and R.sup.2 together are the radical (CH.sub.2).sub.3 --CO, which may be substituted by 1 or 2 methyl groups and whose carbonyl group is bonded to the thiophene ring in the ortho position relative to the sulfur atom,R.sup.3 is cyano or C.sub.1 -C.sub.4 -alkoxycarbonyl,R.sup.4 is C.sub.1 -C.sub.8 -alkyl, cyclohexyl, phenoxy-C.sub.1 -C.sub.4 -alkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted thienyl,R.sup.5 is C.sub.1 -C.sub.4 -alkyl, C.sub.3 -C.sub.7 -alkyl whose alkyl chain is interrupted by 1 or 2 oxygen atoms, or C.sub.1 -C.sub.4 -alkoxy andR.sup.6 is cyanoethyl, phenylethyl or C.sub.3 -C.sub.
    Type: Grant
    Filed: December 4, 1990
    Date of Patent: June 1, 1993
    Assignee: BASF Aktiengesellschaft
    Inventors: Karl-Heinz Etzbach, Guenter Hansen, Gunther Lamm, Helmut Reichelt
  • Patent number: 5175185
    Abstract: Retinoid like activity is exhibited by compounds of the formula ##STR1## R.sub.1 -R.sub.3 independently are hydrogen, lower alkyl, cycloalkyl or lower alkenyl, A and A.sub.1 independently are hydrogen, lower alkyl, cycloalkyl, lower alkenyl, SR.sub.4 or OR.sub.4 where R.sub.4 is lower alkyl, cycloalkyl or lower alkenyl; Y is selected from a group consisting of thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl or oxazolyl; E is lower alkenyl, lower alkynyl, lower cycloalkyl, lower branched chain alkyl, or is characterized by the formula (CH.sub.2).sub.n where n is 0-5, and Z is H, OH, OR.sub.5, OCOR.sub.5, --COOH or a pharmaceutically acceptable salt, ester or amide thereof, --CH.sub.2 OH, CH.sub.2 OR.sub.6, CH.sub.2 OCOR.sub.6, or --CHO, CH(OR.sub.7).sub.2, CHOR.sub.8 O, or COR.sub.9, CR.sub.9 (OR.sub.7).sub.2, CR.sub.9 OR.sub.8 O where R.sub.5 is lower alkyl, phenyl or lower alkylphenyl, R.sub.6 is lower alkyl, phenyl or lower alkylphenyl, R.sub.7 is lower alkyl, R.sub.
    Type: Grant
    Filed: March 14, 1991
    Date of Patent: December 29, 1992
    Assignee: Allergan, Inc.
    Inventor: Roshantha A. S. Chandraratna
  • Patent number: 5166218
    Abstract: Tertiary and secondary amines of the formulas ##STR1## and ##STR2## wherein n is the integer 1 or 2,R is hydrogen, lower-alkanoyl or phenyl-lower-alkanoyl,X.sup.1 is phenoxymethyl optionally mono-fluorinated or mono-chlorinated in the ortho-position,X.sup.2 is lower-alkyl, phenoxymethyl optionally mono-fluorinated or mono-chlorinated in the ortho-position or phenyl optionally monosubstituted by fluorine, chlorine, trifluoromethyl or lower-alkoxy,Y is hydrogen or methyl, andZ is a phenyl or thienyl residue substituted as hereinafter described,and the physiologically and pharmaceutically compatible salts are described. The compounds of formulas I and V-1 have catabolic activity and can be used for the treatment of obesity and diabetes mellitus or for the treatment of conditions which are associated with an increased protein breakdown, or as feed additives for fattening animals. The compounds of formulas I and V-1 can be prepared starting from corresponding primary amines.
    Type: Grant
    Filed: August 12, 1991
    Date of Patent: November 24, 1992
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Leo Alig, Marcel Muller
  • Patent number: 5073184
    Abstract: Compounds of formula (I): ##STR1## and stereoisomers thereof, wherein W is R.sup.1 O.sub.2 C--C.dbd.CH--ZR.sup.2, wherein R.sup.1 and R.sup.2, which are the same or different, are alkyl or fluoroalkyl groups, and Z is either an oxygen or sulphur atom; A is an oxygen or sulphur atom, --NR.sup.3 --, or --CR.sup.4 R.sup.5 --; X, Y and Z.sup.
    Type: Grant
    Filed: April 9, 1990
    Date of Patent: December 17, 1991
    Assignee: Imperial Chemical Industries PLC
    Inventors: Vivienne M. Anthony, John M. Clough, Paul deFraine, Christopher R. A. Godfrey, Kevin Beautement
  • Patent number: 5064863
    Abstract: Tertiary and secondary amines of the formulas ##STR1## wherein n is the integer 1 or 2, p0 R is hydrogen, lower-alkanoyl or phenyl-lower-alkanoyl,X.sup.1 is phenoxymethyl optionally mono-fluorinated or mono-chlorinated in the ortho-position,X.sup.2 is lower-alkyl, phenoxymethyl optionally mono-fluorinated or mono-chlorinated in the ortho-position or phenyl optionally monosubstituted by fluorine, chlorine, trifluoromethyl or lower-alkoxy,Y is hydrogen or methyl, andZ is a phenyl or thienyl residue substituted as hereinafter described,and the physiologically and pharmaceutically compatible salts are described. The compounds of formulas I and V-1 have catabolic activity and can be used for the treatment of obesity and diabetes mellitus or for the treatment of conditions which are associated with an increased protein breakdown, or as feed additives for fattening animals. The compounds of formulas I and V-1 can be prepared starting from corresponding primary amines.
    Type: Grant
    Filed: December 10, 1987
    Date of Patent: November 12, 1991
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Leo Alig, Marcel Muller