Phenoxphenyl Alanines Patents (Class 562/447)
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Publication number: 20150045389Abstract: The present invention is a screening assay for identifying inhibitors of Pseudomonas aeruginosa CFTR Inhibitory Factor as well as compounds identified by the screening assay for use in compositions and methods for ameliorating or treating a respiratory disease such as cystic fibrosis or secondary infection thereof.Type: ApplicationFiled: April 9, 2013Publication date: February 12, 2015Inventors: Dean R. Madden, Christopher D. Bahl, Bruce D. Hammock, Christophe Morisseau
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Patent number: 8759572Abstract: The present invention generally refers to a process for the preparation of L-thyroxine derivatives. More in particular, the present invention relates to a iodination reaction of an aromatic derivative with an appropriate iodinating agent, so to afford the related iodinated compound as disodium salt, which may represent a useful intermediate for the synthesis of the L-thyroxine mono-sodium salt, and the free form thereof.Type: GrantFiled: December 17, 2010Date of Patent: June 24, 2014Assignee: Bracco Imaging S.p.A.Inventors: Carlo Felice Viscardi, Enrico Cappelletti, Laura Galimberti, Sonia Gazzetto, Loredana Sini
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Publication number: 20130261332Abstract: The present invention provides an improved method for preparing, purifying, precipitating, etc., a subject compound for use in a subsequent reaction carried out in suspension. The present invention relies on a precipitating solvent being added to an aqueous solution comprising the subject compound to form a precipitate of the subject compound, which may be further dried and/or purified. Compositions made according to present methods have improved characteristics and properties, such as increased surface and/or reduced density, resulting in a higher reactivity in a subsequent reaction carried out in suspension.Type: ApplicationFiled: May 22, 2013Publication date: October 3, 2013Inventor: Keith R. Latham
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Patent number: 8399518Abstract: Methods and compositions are disclosed for stimulating weight loss and/or lowering triglyceride levels in an individual mammal in need thereof. In an exemplary method, a pharmaceutical composition comprising a therapeutically effective amount of DITPA, and optionally one or more lipid-reducing agents, is administered to an individual mammal to stimulate weight loss, and/or reduce levels of triglyceride and/or lipoprotein in the mammal.Type: GrantFiled: February 27, 2008Date of Patent: March 19, 2013Assignees: University of Arizona Office of Technology Transfer, The United States of America as Represented by the Department of Veterans AffairsInventors: Eugene Morkin, Louis R. Bucalo, Steven Goldman
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Patent number: 7504435Abstract: Administration of a therapeutically effective amount of 3,5-diiodothyropropionic acid stimulates weight loss in patients, lowers triglyceride levels and reduces risk of death or progression of coronary heart disease in patients with metabolic syndrome.Type: GrantFiled: April 13, 2005Date of Patent: March 17, 2009Assignee: The Arizona Board of Regents on Behalf of the University of ArizonaInventors: Cynthia R. Adamson, legal representative, Steven Goldman, Eugene Morkin
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Patent number: 7357835Abstract: A crystalline material sufficiently pure for use in pharmaceuticals may be made by forming a saturated solution of the material, changing the temperature of the solution so it becomes supersaturated, and subjecting the solution to irradiation by high intensity ultrasound, the frequency of the ultrasound being scanned over a range of frequencies. For example the ultrasound may be varied between 19.5 and 20.5 kHz, and this variation may be sinusoidal. Preferably the ultrasound is provided only briefly, say for less than 5 s, before allowing the solution to cool gradually without further irradiation. The ultrasound may be applied using a vessel with an array of ultrasonic transducers attached to a wall, so each transducer radiates no more than 3 W/cm2 yet the power dissipation within the vessel is between 25 and 150 W/litre. This method can reduce the metastable zone width to less than 10 K. It is applicable in particular to aspartame.Type: GrantFiled: May 13, 2003Date of Patent: April 15, 2008Assignee: Accentus PLCInventors: Linda Jane McCausland, John Patrick Perkins
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Patent number: 7163918Abstract: The present invention relates to compositions comprising thyroxine (T4) and triiodothyronine (T3). More specifically, the invention relates to thyroxine (T4) and triiodothyronine (T3) compositions that include a peptide carrier and thyroxine (T4) and triiodothyronine (T3) covalently attached to at least one of the N-terminus, the C-terminus, a side chain of the peptide carrier, and/or interspersed within the peptide chain; methods for protecting and administering thyroxine (T4) and triiodothyronine (T3); and methods for treating thyroid disorders.Type: GrantFiled: May 2, 2002Date of Patent: January 16, 2007Assignee: New River Pharmaceuticals Inc.Inventors: Thomas Piccariello, Lawrence Peter Olon, Alex Saunders Goldstein, James Scott Moncrief, Nancy Johnston Boerth
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Patent number: 7153997Abstract: This invention relates to novel compounds, which are thyroid receptor ligands, and to methods of preparing such compounds. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described herein is administered in a therapeutically effective amount.Type: GrantFiled: July 8, 2003Date of Patent: December 26, 2006Assignees: Karo Bio AB, Bristol-Myers Squibb CompanyInventors: Neeraj Garg, Mahmoud Rahimi Ghadim, Thomas Anders Wilson Ericsson, Lars Johan Malm, Denis Evan Ryono
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Patent number: 7145040Abstract: The present invention provides process useful for the preparation of intermediates which are useful in the preparation of amino acids useful in preparing peptide receptor modulators, for example agonists or partial agonists of such peptide receptors. Such peptide receptor modulators include, for example glucagon like peptide-1 receptor modulators which are useful for the amelioration of the diabetic condition.Type: GrantFiled: June 30, 2005Date of Patent: December 5, 2006Assignee: Bristol-Myers Squibb Co.Inventors: Arvind Mathur, K. Selva Kumar
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Patent number: 6992216Abstract: A method for reducing the particle size of amino acid crystals using ultrasound is discussed.Type: GrantFiled: January 7, 2003Date of Patent: January 31, 2006Assignee: Abbott GmbH & Co. KGInventors: Siegfried Bechtel, Matthias Rauls, Richard Van Gelder, Seth C. Simpson
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Patent number: 6855706Abstract: Specified phenylalanine derivatives and analogues thereof have an antagonistic activity to ? 4 integrin. They are used as therapeutic agents for various diseases concerning ? 4 integrin.Type: GrantFiled: May 20, 2002Date of Patent: February 15, 2005Assignee: Ajinomoto Co., Inc.Inventors: Yasuhiro Tanaka, Toshihiko Yoshimura, Hiroyuki Izawa, Chieko Ejima, Mitsuhiko Kojima, Yuko Satake, Eiji Nakanishi, Nobuyasu Suzuki, Shingo Makino, Manabu Suzuki, Masahiro Murata
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Patent number: 6716877Abstract: A method for treating a patient having congestive heart failure by administering a therapeutically effective amount of 3′,3,5-triiodothyropropionic acid (TRIPROP) or 3,5,3′,5′-tetraiodothyropropionic acid (TETRAPROP). Also described is a method to lower cholesterol blood levels of a patient by administering a therapeutically effective amounts of TRIPROP or TETRAPROP.Type: GrantFiled: February 18, 2003Date of Patent: April 6, 2004Assignee: The Arizona Board of Regents on behalf of the University of ArizonaInventor: Eugene Morkin
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Patent number: 6610710Abstract: Phenylalanine derivatives of the following formula and analogues thereof have an antagonistic activity to &agr;4&bgr;7 integrin and a selectivity toward &agr;4&bgr;1 integrin. They are used as therapeutic agents for various diseases to which &agr;4&bgr;7 integrin relates.Type: GrantFiled: June 28, 2002Date of Patent: August 26, 2003Assignee: Ajinomoto Co., Inc.Inventors: Yasuhiro Tanaka, Toshihiko Yoshimura, Chieko Ejima, Mitsuhiko Kojima, Eiji Nakanishi, Hiroyuki Izawa, Yuko Satake, Nobuyasu Suzuki, Manabu Suzuki, Masahiro Murata
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Patent number: 6337064Abstract: Compounds of formula (I) both in the racemic and optically active forms, are used in MRI diagnostic imaging.Type: GrantFiled: September 25, 2000Date of Patent: January 8, 2002Assignee: Dibra S.p.A.Inventors: Marino Brocchetta, Luisella Calabi, Daniela Palano, Lino Paleari, Fulvio Uggeri
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Patent number: 6229011Abstract: Compounds of the formula: are disclosed which have activity as inhibitors of binding between VCAM-1 and cells expressing VLA-4. Such compounds are useful for treating diseases whose symptoms and/or damage are related to the binding of VCAM-1 to cells expressing VLA-4.Type: GrantFiled: August 21, 1998Date of Patent: May 8, 2001Assignee: Hoffman-La Roche Inc.Inventors: Li Chen, Robert William Guthrie, Tai-Nang Huang, Achyutharao Sidduri, Jefferson Wright Tilley, Kenneth Gregory Hull
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Patent number: 5958979Abstract: The present invention relates to stabilized medicaments containing thyroid hormone the stabilizing component of which is sodium thiosulfate in a mass ratio of thyroid hormone to sodium thiosulfate of 1:0.1 to 1:50 and processes for preparing such medicaments.Type: GrantFiled: April 8, 1998Date of Patent: September 28, 1999Assignee: Henning Berlin GmbH & Co.Inventors: Wolfgang Lahr, Andrea Friese, Guido Weickgenannt
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Patent number: 5917087Abstract: Improvements to a six stage process for production of sodium l-thyroxine from l-tyrosine ?described in U.S. Pat. No. 2,889,363 and U.S. Pat. No. 2,889,364 (Baxter)! are described, the improvements comprising the oxidative coupling of a diiodo-l-thyrosine to form a biphenyl ether derivative, catalysed by a manganese salt in which the amine and acid functionally of the diiodo-l-thyrosine have been protected by suitable protecting groups, characterised in that the reaction is performed at a pressure of about 20 atmospheres in the presence of an organic amine additive using a gaseous oxidant comprising oxygen and optionally an inert diluent. The process optionally further comprises acid hydrolysis of the biphenyl ether derivative with hydrochloric acid to form a l-thyroxine hydrochloride salt and generation of sodium-l-thyroxine from the l-thyroxine hydrochloride salt.Type: GrantFiled: April 7, 1997Date of Patent: June 29, 1999Assignee: Knoll AktiengesellschaftInventor: Paul Frederick Coe
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Patent number: 5668176Abstract: Phenoxyphenylacetic acids and derivatives of the general structural formula I ##STR1## have endothelin antagonist activity and are useful in treating cardiovascular disorders, such as hypertension, postischemic renal failure, vasospasm, cerebral and cardiac ischemia, myocardial infarction, endotoxic shock, benign prostatic hyperplasia, inflammatory diseases including Raynaud's disease and asthma.Type: GrantFiled: October 18, 1996Date of Patent: September 16, 1997Assignee: Merck & Co. Inc.Inventors: Scott W. Bagley, Theodore P. Broten, Prasun K. Chakravarty, Daljit S. Dhanoa, Kenneth J. Fitch, William J. Greenlee, Nancy Jo Kevin, Gerard R. Kieczykowski, Douglas J. Pettibone, James R. Tata, Ralph A. Rivero, Thomas F. Walsh, David L. Williams, Jr., Jay M. Matthews, Richard B. Toupence
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Patent number: 5359093Abstract: Immunoassay methods and reagents for the specific quantification of thyroxine in a test sample are disclosed employing antibodies prepared with thyroxine derivatives of the formula: ##STR1## wherein P is an immunogenic carrier material and X is a linking moiety. The present invention also describes the synthesis of unique labelled reagent of the formula: ##STR2## wherein Q is a detectable moiety and W is a linking moiety, preferably fluorescein or a fluorescein derivative.Type: GrantFiled: November 6, 1992Date of Patent: October 25, 1994Assignee: Abbott LaboratoriesInventors: Maciej Adamczyk, Donald D. Johnson, Phillip G. Mattingly, Diana E. Clarisse, Joan D. Tyner, Mary M. Perkowitz
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Patent number: 5288901Abstract: There are provided important pyrroline and glycine intermediates, methods for the preparation of said intermediates and the use thereof in the manufacture of arylpyrrole insecticidal agents.Type: GrantFiled: April 8, 1992Date of Patent: February 22, 1994Assignee: American Cyanamid CompanyInventors: Robert F. Doehner, Jr., Jerry M. Barton, David G. Kuhn
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Patent number: 5219764Abstract: Hapten-biotin conjugates in which the hapten is linked with biotin via a spacer, which has 26 to 40 atoms in its chain and contains at least 5 heteroatoms, are novel and are suitable, in particular for use in a competitive homogeneous immunoassay in which the agglutination which occurs in the reaction is evaluated by turbidimetric or nephelometric measurements.Type: GrantFiled: April 10, 1991Date of Patent: June 15, 1993Assignee: Boehringer Mannheim GmbHInventors: Erasmus Huber, Dietmar Zdunek, Christian Klein, Roland Schenk
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Patent number: 5169984Abstract: A method for synthesizing N-bromoacetyl-3,3',5-triiodo-L-thyronine which involves subjecting 3,3', 5-triiodo-L-thyronine to a one-step bromacetylation reaction wherein 3,3', 5-triiodo-L-thyronine and bromoacetyl bromide are refluxed together in a solution of ethyl acetate. After formation the N-bromoacetyl-3,3'-triiodo-L-thyronine is purified by fractionation utilizing high speed countercurrent chromatography. Labeled N-bromoacetyl-3,3'-5-triiodo-L-thryonine may be made by a one-step bromacetylation reaction by reducing either [.sup.125 I]T.sub.3 or [.sup.14 C]T.sub.3 with bromoacetyl bromide.Type: GrantFiled: September 10, 1990Date of Patent: December 8, 1992Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Hans J. Cahnmann, Yoichiro Ito
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Patent number: 4826876Abstract: This invention relates to chemical compounds which have selective thyromimetic activity. A compound of this invention is 3,5-dibromo-3'-[6-oxo-3(1H)-pyridazinyl-methyl]-thyronine.Type: GrantFiled: December 21, 1987Date of Patent: May 2, 1989Assignee: Smith Kline & French Laboratories LimitedInventors: David Ellis, John C. Emmett, Anthony H. Underwood, Paul D. Leeson
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Patent number: 4820860Abstract: The invention relates to novel thyronine derivatives of the formula ##STR1## in which n is 10-400, R denotes H, alkyl or N-carbonylthyronine, R.sup.1 and R.sup.2 are identical or different and denote hydrogen or iodine, and R.sup.3 denotes H or alkyl, a process for the preparation of the compounds, and their use when carrying out immunoassays.Type: GrantFiled: August 21, 1987Date of Patent: April 11, 1989Assignee: Hoechst AktiengesellschaftInventors: Hans Wissmann, Guido Simons, Helmut Strecker, deceased
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Patent number: 4801742Abstract: Formylating the amino nitrogen of an alkali metal salt of an amino carboxylic acid, by reacting the salt with an alkyl formate in an alkanol solvent. In one embodiment, the alkyl formate is added to the reaction as such; in another embodiment, the alkyl formate is formed in situ by reaction of carbon monoxide with the alkanol solvent in the presence of the alkali metal salt of the amino carboxylic acid. The process provides a new class of compounds, the alkali metal salts of N-formyl-aspartic acids.Type: GrantFiled: July 17, 1987Date of Patent: January 31, 1989Assignee: W. R. Grace & Co.-Conn.Inventors: Jennifer M. Quirk, Charles G. Carter, Robert J. Kupper
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Patent number: 4741897Abstract: The present invention relates to new compounds of the general formula: ##STR1## where X is iodine or hydrogen; A is a linking portion; and R is an iodinatable aryl or heteroaryl group having electron donating substituents. These compounds are useful precursors to the iodinated thyroid hormones for radioimmunoassay determination of thyroid hormones in biological fluids.Type: GrantFiled: July 8, 1986Date of Patent: May 3, 1988Assignee: Baxter TravenolInventors: Judith Andrews, Christine Burns, James Quick
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Patent number: 4675439Abstract: A process for preparing an N-acylphenylalanine represented by the formula (II): ##STR1## wherein R.sub.3 and R.sub.4 mean individually a hydrogen atom or an alkyl, alkoxy, phenoxy, hydroxy or methylenedioxy group, and R denotes a methyl or phenyl group, which comprises catalytically reducing an N-acyl-.beta.-phenylserine represented by the formula (I): ##STR2## wherein R.sub.1 and R.sub.2 mean individually a hydrogen atom or an alkyl, alkoxy, phenoxy, benzyloxy or methylenedioxy group, and R has the same meaning as defined in the formula (II), in the presence of a reducing catalyst or both reducing catalyst and acid, in a solvent.Type: GrantFiled: November 4, 1985Date of Patent: June 23, 1987Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Ryuichi Mita, Toshio Katoh, Chojiro Higuchi, Akihiro Yamaguchi
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Patent number: 4613691Abstract: Amino acids can be easily prepared by reducing unsaturated hydantoins to the corresponding saturated hydantoins by hydrogenating the unsaturated hydantoin using either Raney Nickel catalyst in the presence of more than a stoichiometric amount of caustic or by using zinc and hydrochloric acid followed by hydrolyzing the resultant composition with at least 3 molar equivalents of an alkali metal hydroxide to produce a racemate of an alpha amino acid. The amino acid in suitable derivative form can then be resolved particularly using a two-phase solvent system. The residual isomer of the amino acid remaining after the resolution process can then be racemized using either pyridoxal-5-phosphate or an aliphatic acid in combination with an aldehyde or a ketone. By these procedures, it is possible to obtain high yields of amino acids.Type: GrantFiled: July 8, 1985Date of Patent: September 23, 1986Assignee: Stauffer Chemical CompanyInventors: Stanley B. Mirviss, Mark W. Empie
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Patent number: 4612388Abstract: Disclosed herein is a process for producing an N-acyl-substituted or unsubstituted phenylalanine comprising hydrolyzing a 2-substituted-4-substituted or unsubstituted benzylidene-5-oxazolone with alkali, adjusting pH of the reaction solution containing its hydrolysis product with acid at 5-9 and reducing the resultant reaction solution catalytically in the presence of a palladium or platinum reducing catalyst.In accordance with the process of the present invention, time duration required for effecting the reduction can be shortened markedly in comparison with the reduction in an aqueous strong alkaline solution. Moreover, the catalyst recovered after completion of the reduction can be used repeatedly without any additional treatment and without any observed lowering in its activity. Accordingly, the reduction using the recovered catalyst may proceed in practically the same time as in the case of using a fresh catalyst.Type: GrantFiled: April 3, 1985Date of Patent: September 16, 1986Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Ryuichi Mita, Toshio Katoh, Chojiro Higuchi, Akihiro Yamaguchi
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Patent number: 4540792Abstract: This invention relates to a process for the preparation of free L .alpha.-amino acids by the complete conversion of their D antipodes taken individually or possibly in racemic mixtures.The process according to the present invention is characterized in that the D antipodes of an ester of said .alpha.-amino acid is racemized in the presence of a chemical catalyst formed by at least one aromatic aldehyde corresponding to the general formula: ##STR1## wherein: Ar represents an aromatic ring optionally containing a heteroatom, such as nitrogen, andB represents a basic function,to produce a mixture in dynamic equilibrium of the two forms D and L of said ester, the ester which is present in the L form is hydrolyzed enzymatically and irreversibly to produce the corresponding stereostable L .alpha.-amino acid, said stages of chemical racemization and of enzymatic hydrolysis being carried out under identical reaction conditions, and the free L .alpha.-amino acid is recovered.Type: GrantFiled: March 7, 1983Date of Patent: September 10, 1985Assignees: Centre National de la Recherche Scientifique, Institut National de la Sante et de la Reserche MedicaleInventors: Auguste Commeyras, Aldo Previero, Martine Pugniere
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Patent number: 4452783Abstract: Aminoacid and peptide derivatives of the formula:A--NH--R.sub.1 --CO].sub.x [NH--R.sub.2 --CO].sub.y NH--R.sub.4 --COOHin which A, R.sub.1, R.sub.2, x and y have the meanings specified in claim 1 for formula I, and R4 is a residue of an .alpha.-aminoacid which, when A is 4-allyloxy-3-chloro-phenylacetyl and x and y are 0, contains at least 2 carbon atoms, and their physiologically acceptable salts and lower alkyl ester.These compounds and 4-allyloxy-3-chloro-phenylacetylglycine have anti-inflammatory activity and pharmaceutical compositions containing them are described.Type: GrantFiled: April 21, 1982Date of Patent: June 5, 1984Inventors: Robert E. Marks, James S. Burton, John A. Elvidge, Saresh Shah
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Patent number: 4423227Abstract: Process for the preparation of reactive, couplable derivatives of the thyroid hormones 3,3',5-triiodothyronine (T.sub.3) and 3,3',5,5'-tetraiodothyronine (T.sub.4) by reaction with reactive carboxylic acid derivatives, which process comprises sylylating all the functional groups of the thyroid hormone by reaction with a reactive triorganosylyl derivative and then reacting the persylylated derivative of the thyroid hormone thus obtained with an activated carboxylic acid derivative.Type: GrantFiled: September 30, 1981Date of Patent: December 27, 1983Assignee: Boehringer Mannheim GmbHInventors: Hans-Georg Batz, Winfried Albert, Helmut Lenz, Hans-Ralf Linke, Fritz Stahler
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Patent number: 4399121Abstract: Immunogen conjugates comprising N-aminoalkyl derivatives of iodothyronines, e.g., thyroxine and its lower alkyl esters, coupled to an immunogenic carrier material, and antibodies raised against such immunogen conjugates.Type: GrantFiled: March 29, 1982Date of Patent: August 16, 1983Assignee: Miles Laboratories, Inc.Inventors: James P. Albarella, Robert J. Carrico, Thomas M. Li
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Patent number: 4358604Abstract: N-Aminoalkyl derivatives of iodothyronines, e.g., thyroxine and its lower alkyl esters, immunogen conjugates comprising the derivatives coupled to an immunogenic carrier material, and antibodies raised against such immunogen conjugates.Type: GrantFiled: November 4, 1981Date of Patent: November 9, 1982Assignee: Miles Laboratories, Inc.Inventors: James P. Albarella, Robert J. Carrico, Thomas M. Li
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Patent number: 4311853Abstract: Novel Selenium derivatives of thyroxine and tri-iodothyronine have the formula: ##STR1## wherein M is I or H and either (a) R.sub.1 is OH or a carboxyl protecting group and R.sub.2 contains at least one Se, preferably .sup.75 Se, atom or (b) R.sub.2 is H or an amino protecting group and R.sub.1 contains at least one Se, preferably .sup.75 Se, atom.The compounds are useful in dual isotope assays of thyroid function.Type: GrantFiled: January 30, 1980Date of Patent: January 19, 1982Assignee: The Radiochemical Centre LimitedInventor: Gavin M. Cree
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Patent number: 4261919Abstract: Process for the homogeneous catalytic hydrogenation of .beta.-substituted-.alpha.-acylamido-acrylic acids which yields, after hydrogenation, an optically active mixture. The process comprises the hydrogenation of .beta.-substituted-.alpha.-acylamidoacrylic acids in the presence of an optically active coordinated metal complex hydrogenation catalyst, in which the metal is selected from the group consisting of rhodium, iridium, ruthenium, osmium, palladium and platinum.This process is a generalized process for any asymmetric hydrogenation of .beta.-substituted-.alpha.-acylamido-acrylic acids in which one .alpha.-amino acid enantiomorph is the desired end-product. It is especially useful for the preparation of .alpha.-amino acids found in nature which possess optical activity and which have a hydrogen attached to the asymmetric center.This invention also relates to new optically active coordinated metal complex hydrogenation catalysts.Type: GrantFiled: September 5, 1978Date of Patent: April 14, 1981Assignee: Monsanto CompanyInventors: William S. Knowles, Milton J. Sabacky
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Patent number: 4133753Abstract: The separation of constituents is carried out in such a way that a mixed amino acid sample is supplied to a separation column packed with a cation exchange resin and that, during the analysis of the single sample, five sorts of elutes of different compositions are supplied to the separation column in succession and by stages. The pH of the elute at the second stage is held higher than that of the elute at the first stage, and the pH's of the elutes at the third to fifth stages are held successively higher. However, the pH of the elute at the third stage is held lower than that of the elute at the second stage. On the other hand, the concentrations of counter ions contained in the elutes at the first to fifth stages are held successively higher inversely to the order in which the elutes are supplied. Notwithstanding that the pH of the elute at the third stage is lowered, the broadening of a component peak can be prevented by the increase of the counter ion concentration.Type: GrantFiled: October 26, 1977Date of Patent: January 9, 1979Assignee: Hitachi, Ltd.Inventors: Seiji Takeuchi, Kazunori Fujita