Halogen Attached Directly Or Indirectly To The Hetero Ring By Nonionic Bonding Patents (Class 549/73)
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Patent number: 8642786Abstract: 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: GrantFiled: March 15, 2013Date of Patent: February 4, 2014Assignee: Nissan Chemical Industries, Ltd.Inventors: Kazufumi Yanagihara, Shingo Umezawa, Katsuaki Miyaji
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Publication number: 20130144071Abstract: 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: ApplicationFiled: January 30, 2013Publication date: June 6, 2013Applicants: NIPPOH CHEMICALS CO., LTD., JAPAN SCIENCE AND TECHNOLOGY AGENCYInventors: Japan Science and Technology Agency, Nippoh Chemicals Co., Ltd.
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Publication number: 20110049427Abstract: 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: ApplicationFiled: March 30, 2009Publication date: March 3, 2011Applicant: MERCK PATENT GESELLSCHAFTInventors: Axel Jansen, Detlef Pauluth, Harald Hirschmann, Markus Czanta
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Publication number: 20100278733Abstract: 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: ApplicationFiled: May 22, 2007Publication date: November 4, 2010Inventors: Morio Nakayama, Mamoru Haratake, Masahiro Ono
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Patent number: 7799825Abstract: 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: GrantFiled: February 14, 2007Date of Patent: September 21, 2010Assignee: Istituto di Ricerche di Biologia Molecolare P. Angeletti SpAInventors: Federica Ferrigno, Philip Jones, Ester Muraglia, Jesus Maria Ontoria Ontoria, Rita Scarpelli, Carsten Schultz-Fademrecht
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Patent number: 7745483Abstract: 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: GrantFiled: January 22, 2005Date of Patent: June 29, 2010Assignee: Bayer CropScience AGInventors: Ralf Dunkel, Hans-Ludwig Elbe, Jörg Nico Greul, Benoit Hartmann, Peter Dahmen, Karl-Heinz Kuck, Ulrike Wachendorff-Neumann
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Publication number: 20100075946Abstract: The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.Type: ApplicationFiled: June 20, 2006Publication date: March 25, 2010Applicant: Actelion Pharmaceuticals Ltd.Inventors: Martin Bolli, David Lehmann, Boris Mathys, Claus Mueller, Jörg Velker
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Publication number: 20100029745Abstract: 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: ApplicationFiled: December 28, 2007Publication date: February 4, 2010Inventor: Jean-Francois Delhomel
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Publication number: 20090076101Abstract: 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: ApplicationFiled: February 14, 2007Publication date: March 19, 2009Inventors: Federica Ferrigno, Philip Jones, Ester Muraglia, Jesus Maria Ontoria Ontoria, Rita Scarpelli, Carsten Schultz-Fademrecht
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Patent number: 7365094Abstract: 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: GrantFiled: December 17, 2003Date of Patent: April 29, 2008Assignee: 4SC AGInventors: Johann Leban, Stefan Tasler
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Patent number: 7332518Abstract: 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: GrantFiled: January 24, 2002Date of Patent: February 19, 2008Assignee: Syngenta Crop Protection, Inc.Inventors: Harald Walter, Stephan Trah
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Patent number: 7211679Abstract: 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: GrantFiled: March 9, 2005Date of Patent: May 1, 2007Assignee: 3M Innovative Properties CompanyInventors: Christopher P. Gerlach, David A. Ender, Dennis E. Vogel
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Patent number: 7034053Abstract: 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: GrantFiled: December 17, 2001Date of Patent: April 25, 2006Assignee: SmithKline Beecham CorporationInventors: David N. Deaton, Barry George Shearer, David Edward Uehling
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Patent number: 6835745Abstract: 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: GrantFiled: January 10, 2003Date of Patent: December 28, 2004Assignee: WyethInventors: Richard D. Coghlan, William F. Fobare, Heather A. Harris, James C. Keith, Jr., Leo M. Albert
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Patent number: 6747057Abstract: 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), hyType: GrantFiled: December 20, 2002Date of Patent: June 8, 2004Assignees: 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
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Patent number: 6627652Abstract: 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: GrantFiled: April 20, 1995Date of Patent: September 30, 2003Assignee: Allergan, Inc.Inventor: Roshantha A. S. Chandraratna
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Patent number: 6566375Abstract: 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: GrantFiled: April 26, 2001Date of Patent: May 20, 2003Assignee: WyethInventor: Thomas J. Commons
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Patent number: 6323214Abstract: 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: GrantFiled: September 17, 1998Date of Patent: November 27, 2001Assignee: Medco Research, IncInventor: Pier Giovanni Baraldi
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Patent number: 6313302Abstract: 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: GrantFiled: January 26, 2001Date of Patent: November 6, 2001Assignee: Pfizer Inc.Inventors: Fumitaka Ito, Hiroshi Kondo
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Patent number: 6248773Abstract: The invention relates to the use of cyclopentane heptan(ene)oic acid, 2-heteroarylalk(en)yl derivatives as ocular hypotensives.Type: GrantFiled: August 22, 2000Date of Patent: June 19, 2001Assignee: Allergan Sales, Inc.Inventor: Robert M. Burk
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Patent number: 6080861Abstract: A compound is disclosed having the formula: ##STR1## The compound is useful as an active ingredient in a herbicidal composition.Type: GrantFiled: November 3, 1998Date of Patent: June 27, 2000Assignee: American Cyanamid CompanyInventors: Gary Mitchell Karp, Michael Edward Condon, Axel Kleemann
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Patent number: 6025383Abstract: 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: GrantFiled: June 3, 1998Date of Patent: February 15, 2000Assignee: Bayer AktiengesellschaftInventors: Reiner Fischer, Jacques Dumas, Thomas Bretschneider, Bernd Gallenkamp, Folker Lieb, Konrad Wernthaler, Christoph Erdelen, Ulrike Wachendorff-Neumann, Norbert Mencke, Andreas Turberg
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Patent number: 6013664Abstract: 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: GrantFiled: May 26, 1999Date of Patent: January 11, 2000Assignee: Bayer AktiengesellschaftInventors: Reiner Fischer, Norbert Lui, Stefan Dutzmann, Gerd Hanssler
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Patent number: 6004948Abstract: 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: GrantFiled: September 3, 1998Date of Patent: December 21, 1999Assignee: Nycomed Austria GmbHInventors: Heinz Blaschke, Peter Kremminger, Michael Hartmann, Harald Fellier, Jorg Berg, Thomas Christoph, Franz Rovenszky, Dagmar Stimmeder
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Patent number: 6005113Abstract: 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: GrantFiled: May 14, 1997Date of Patent: December 21, 1999Assignee: Molecular Probes, Inc.Inventors: Yexin Wu, Dieter H. Klaubert, Hee Chol Kang, Yu-Zhong Zhang
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Patent number: 5856323Abstract: 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: GrantFiled: June 7, 1995Date of Patent: January 5, 1999Assignee: CytoMed, Inc.Inventors: Xiong Cai, Sajjat Hussoin, San-Bao Hwang, David Killian, T. Y. Shen
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Patent number: 5834498Abstract: 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: GrantFiled: October 7, 1996Date of Patent: November 10, 1998Assignee: AllerganInventor: Robert M. Burk
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Patent number: 5789437Abstract: 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: GrantFiled: October 4, 1996Date of Patent: August 4, 1998Assignee: Bayer AktiengesellschaftInventors: Hans-Ludwig Elbe, Lutz Assmann, Ralf Tiemann, Uta Ecker, Gerd Hanssler, Heinz-Wilhelm Dehne
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Patent number: 5747518Abstract: 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: GrantFiled: April 3, 1996Date of Patent: May 5, 1998Assignee: 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
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Patent number: 5739140Abstract: 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: GrantFiled: October 23, 1996Date of Patent: April 14, 1998Assignee: Monsanto CompanyInventors: William P. Clinton, Jim I. McLoughlin, Anita E. Otal, John J. Parlow, Dennis P. Phillion, Ajit S. Shah
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Patent number: 5650522Abstract: 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: GrantFiled: June 14, 1996Date of Patent: July 22, 1997Assignee: Erregierre S.P.A.Inventors: Antonio Bonaldi, Massimo Ferrari, Egidio Molinari, Fabrizio Zinetti
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Patent number: 5648486Abstract: 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: GrantFiled: May 12, 1993Date of Patent: July 15, 1997Assignee: CytoMed, Inc.Inventors: Xiong Cai, Sajjat Hussoin, San-Bao Hwang, David Killian, T. Y. Shen
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Patent number: 5610319Abstract: 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: GrantFiled: June 7, 1995Date of Patent: March 11, 1997Assignee: Agouron Pharmaceuticals, Inc.Inventors: Michael D. Varney, William H. Romines, Cynthia L. Palmer
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Patent number: 5608082Abstract: 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: GrantFiled: July 28, 1994Date of Patent: March 4, 1997Assignee: Agouron Pharmaceuticals, Inc.Inventors: Michael D. Varney, William H. Romines
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Patent number: 5563250Abstract: 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: GrantFiled: May 13, 1994Date of Patent: October 8, 1996Assignee: NeoRx CorporationInventors: Mark D. Hylarides, Ananthachari Srinivasan, Jeffrey N. Fitzner, Vivekananda M. Vrudhula
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Patent number: 5527955Abstract: 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: GrantFiled: December 23, 1993Date of Patent: June 18, 1996Assignee: John Wyeth & Brother, LimitedInventors: Michael C. W. Minchin, John F. White
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Patent number: 5480902Abstract: 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: GrantFiled: August 31, 1993Date of Patent: January 2, 1996Assignee: American Cyanamid CompanyInventors: Roger W. Addor, Joseph A. Furch, III, Laurelee A. Duncan
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Patent number: 5470977Abstract: 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: GrantFiled: March 14, 1995Date of Patent: November 28, 1995Assignee: Eli Lilly and CompanyInventors: John M. Schaus, Craig S. Hoechstetter, Diane Huser, Charles J. Paget, Robert D. Titus
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Patent number: 5463083Abstract: 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: GrantFiled: January 6, 1994Date of Patent: October 31, 1995Assignee: Cytomed, Inc.Inventors: Tesfaye Biftu, Xiong Cai, Sajjet Hussion, Gurmit Grewal, T. Y. Shen
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Patent number: 5455265Abstract: 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: GrantFiled: February 11, 1993Date of Patent: October 3, 1995Assignee: Allergan, Inc.Inventor: Roshantha A. S. Chandraratna
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Patent number: 5434151Abstract: 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: GrantFiled: August 24, 1992Date of Patent: July 18, 1995Assignee: CytoMed, Inc.Inventors: Xiong Cai, Sajjat Hussoin, San-Bao Hwang, David Killian, T. Y. Shen
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Patent number: 5424448Abstract: A process for synthesizing carbonic anhydrase inhibitors is disclosed.Type: GrantFiled: January 14, 1994Date of Patent: June 13, 1995Assignee: Alcon Laboratories, Inc.Inventors: William D. Dean, Paul W. Zinke, Steven J. Sproull, Michael E. Deason, Raymond E. Conrow, Anura P. Dantanarayana
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Patent number: 5371240Abstract: 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: GrantFiled: November 30, 1992Date of Patent: December 6, 1994Assignee: Torcan Chemical Ltd.Inventor: Clarke Slemon
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Patent number: 5358938Abstract: 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: GrantFiled: July 13, 1992Date of Patent: October 25, 1994Assignee: CytoMed, Inc.Inventors: Xiong Cai, Saijat Hussoin, San-Bao Hwang, David Killian, T. Y. Shen
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Patent number: 5235068Abstract: 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: GrantFiled: July 21, 1992Date of Patent: August 10, 1993Assignee: Sumitomo Chemical Company, LimitedInventors: Masayoshi Minai, Michitada Kondo, Yuji Ueda, Seiichi Kai, Takayuki Higashii
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Patent number: 5216139Abstract: 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: GrantFiled: December 4, 1990Date of Patent: June 1, 1993Assignee: BASF AktiengesellschaftInventors: Karl-Heinz Etzbach, Guenter Hansen, Gunther Lamm, Helmut Reichelt
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Patent number: 5175185Abstract: 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: GrantFiled: March 14, 1991Date of Patent: December 29, 1992Assignee: Allergan, Inc.Inventor: Roshantha A. S. Chandraratna
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Patent number: 5166218Abstract: 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: GrantFiled: August 12, 1991Date of Patent: November 24, 1992Assignee: Hoffmann-La Roche Inc.Inventors: Leo Alig, Marcel Muller
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Patent number: 5073184Abstract: 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: GrantFiled: April 9, 1990Date of Patent: December 17, 1991Assignee: Imperial Chemical Industries PLCInventors: Vivienne M. Anthony, John M. Clough, Paul deFraine, Christopher R. A. Godfrey, Kevin Beautement
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Patent number: 5064863Abstract: 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: GrantFiled: December 10, 1987Date of Patent: November 12, 1991Assignee: Hoffmann-La Roche Inc.Inventors: Leo Alig, Marcel Muller