Phenylalanines Patents (Class 560/40)
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Patent number: 5658943Abstract: Novel antagonists of endothelin are described, as well as novel intermediates used in their preparation, methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, essential, renovascular, malignant and pulmonary hypertension, cerebral infarction, myocardial ischemia, cerebral ischemia, congestire heart failure and subarachnoid hemorrhage.Type: GrantFiled: January 5, 1995Date of Patent: August 19, 1997Assignee: Warner-Lambert CompanyInventors: Kent Alan Berryman, Xue-Min Cheng, Annette Marian Doherty, Jeremy John Edmunds, Sylvester Klutchko
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Patent number: 5650508Abstract: A novel class of peptide .alpha.-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M.sub.1 --AA--NH--CHR.sub.2 --CO--CO--NR.sub.3 R.sub.4, M.sub.1 --AA.sub.2 --AA.sub.1 --CO--NR.sub.3 R.sub.4, M.sub.1 --AA--AA--AA--CO--NR.sub.3 R.sub.4, M.sub.1 --AA--AA--AA--AA--CO--NR.sub.3 R.sub.4, or M.sub.1 --AA--CO--NR.sub.3 R.sub.4.Type: GrantFiled: October 6, 1995Date of Patent: July 22, 1997Assignee: Georgia Tech Research CorporationInventor: James C. Powers
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Patent number: 5610297Abstract: A novel class of peptide .alpha.-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M.sub.1 -AA-NH--CHR.sub.2 --CO--CO--NR.sub.3 R.sub.4, M.sub.1 -AA.sub.2 -AA.sub.1 -CO--NR.sub.3 R.sub.4, M.sub.1 -AA-AA-AA-CO--NR.sub.3 R.sub.4, M.sub.1 -AA-AA-AA-AA-CO--NR.sub.3 R.sub.4, or M.sub.1 -AA-CO--NR.sub.3 R.sub.4.Type: GrantFiled: October 6, 1995Date of Patent: March 11, 1997Assignee: Georgia Tech Research Corp.Inventor: James C. Powers
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Patent number: 5591886Abstract: Disclosed herein is a crystallization apparatus for use in the crystallization of L-.alpha.-aspartyl-L-phenylalanine methyl ester. The stirring blade of the crystallization apparatus is composed of a band plate member for sweeping the bottom of a vessel and rod- or band plate-members arranged thereon and extending substantially vertically and horizontally.Type: GrantFiled: June 16, 1995Date of Patent: January 7, 1997Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Hiroshi Ichiki, Ryoichi Taneda, Hiroyuki Itoh, Yoshitsugu Kono
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Patent number: 5587507Abstract: A method for preparing diphenol compounds, which method includes the steps of coupling a hydroxyphenyl carboxylic acid with a L-tyrosine ester in a water-miscible organic reaction solvent containing a carbodiimide capable of forming a water-soluble urea by-product, thereby forming a diphenol reaction product; and combining the reaction mixture with an amount of water effective to precipitate the diphenol as a water-immiscible organic phase, so that a water-immiscible organic phase is formed containing the diphenol reaction product. New diphenol monomers and polymers polymerized therefrom are also disclosed.Type: GrantFiled: March 31, 1995Date of Patent: December 24, 1996Assignee: Rutgers, The State UniversityInventors: Joachim B. Kohn, Kimberly A. Hooper
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Patent number: 5587514Abstract: A process for the synthesis of hydroxyethylene dipeptide isosteres from .alpha.-N,N-di(protected)-amino(alkyl or substituted alkyl)methyl ketones that can be efficiently carried out on an industrial scale. The process proceeds with excellent diastereoselectivity and chemical efficiency, and can be used to prepare a wide variety of hydroxyethylene dipeptide isosteres for a variety of uses, including as HIV-1 protease inhibitors and renin inhibitors.Type: GrantFiled: November 8, 1993Date of Patent: December 24, 1996Assignee: Emory UniversityInventors: Dennis C. Liotta, Bharat R. Lagu
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Patent number: 5583248Abstract: Compounds of the formula: ##STR1## wherein R.sup.1 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aralkanoyl, heterocyclylcarbonyl or a group of the formula: ##STR2## R.sup.2 is alkyl, cycloalkylalkyl or aralkyl; R.sup.3 is hydrogen and R.sup.4 is hydroxy or R.sup.3 and R.sup.4 together are oxo; R.sup.5 is alkoxycarbonyl or alkylcarbamoyl; R.sup.6 and R.sup.7 together are trimethylene or tetramethylene optionally substituted by alkyl or on adjacent carbon atoms by tetramethylene; R.sup.8 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aroyl, aralkanoyl or heteroeyelylearbonyl; and R.sup.9 is alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, cyanoalkyl, carbamoyl-alkyl, alkylthioalkyl, alkoxyalkyl or alkoxycarbonylalkyl:and pharmaceutically acceptable acid addition salts of those compounds of formula I which are basic, inhibit aspartyl proteases of viral origin and can be used in the form of medicaments for the prophylaxis or treatment of viral infections.Type: GrantFiled: April 5, 1995Date of Patent: December 10, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Joseph A. Martin, Gareth J. Thomas
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Patent number: 5514716Abstract: This disclosure relates to a novel class of hydroxamic and carboxylic acid based matrix metalloproteinase inhibitor derivatives. The disclosure further relates to pharmaceutical compositions containing such compounds and to the use of such compounds and compositions in the treatment of matrix metalloproteinase induced diseases.Type: GrantFiled: February 25, 1994Date of Patent: May 7, 1996Assignee: Sterling Winthrop, Inc.Inventors: Madhusudhan R. Gowravaram, Jeffrey Johnson, Ewell R. Cook, Robert C. Wahl, Alan M. Mathiowetz, Bruce E. Tomczuk, Ashis K. Saha
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Patent number: 5514810Abstract: The invention relates to a process for the production of diethylenetriaminepentacarboxylic acid tetraesters of general formula I ##STR1## in which R.sup.1 and Z have different meanings.Type: GrantFiled: June 5, 1995Date of Patent: May 7, 1996Assignee: Schering AktiengesellschaftInventors: Johannes Platzek, Ulrich Niedballa, Bernd Radeuchel
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Patent number: 5506279Abstract: The invention provides novel acrylamide functional disubstituted acetyl aryl ketones and a process for their preparation in high yields uncontaminated by difunctional material. The invention further provides photocrosslinkable compositions comprising one or more ethylenically-unsaturated monomers and as photoinitiator the acrylamide functional disubstituted acetyl aryl ketone of the invention. The compositions are useful for the preparation of films and coatings, particularly pressure-sensitive adhesive coatings.Type: GrantFiled: May 3, 1994Date of Patent: April 9, 1996Assignee: Minnesota Mining and Manufacturing CompanyInventors: Gaddam N. Babu, Greggory S. Bennett, Kejian Chen, Steven M. Heilmann, Howell K. Smith, II, Louis E. Winslow
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Patent number: 5503776Abstract: An N-acylamino acid compound represented by the general formula (1):R--CO--(NH--X--CO).sub.n --OR.sup.1 (1)wherein (NH--X--CO) is an amino acid residue, X in (NX--X--CO) is variable with the kind of amino acid to be used, R--CO is a saturated or an unsaturated fatty acid residue having 6 to 24 carbon atoms, R.sup.1 is hydrogen atom, sodium atom, potassium atom, or methyl group and n is an integer in the range of from 1 to 3, indicating that at least one histidine is contained as a component amino acid is disclosed, which is obtained by causing an N-hydroxysuccinimide ester to react with an amino acid or a peptide.The compound excels in antioxidizing power, emulsifying power, antibacterial power, chelating power, infrared absorbing power, and humidity-retaining power.Type: GrantFiled: December 21, 1994Date of Patent: April 2, 1996Assignees: National Food Research Institute Ministry of Agriculture, Forestry and Fisheries, CCI CorporationInventors: Hironobu Murase, Tsutomu Kunieda, Akihiko Nagao, Junji Terao
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Patent number: 5501712Abstract: The problems in crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl ester, namely, problems in crystal slurry properties in solid-liquid separation, scaling at heat transfer surfaces, and the like, are solved by a method for crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl ester which comprises cooling a solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester by indirect heat exchange with a coolant while stirring, wherein the solution is cooled by circulating a coolant while continuously adding an aqueous solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester dropwise to a crystallizing solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester having a temperature difference of not greater than 20.degree. C. from the coolant, thereby to keep a temperature difference of not greater than 20.degree. C. between the coolant and the crystallizing solution.Type: GrantFiled: October 21, 1994Date of Patent: March 26, 1996Assignee: Ajinomoto Co., Inc.Inventors: Sou Abe, Shinichi Kishimoto
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Patent number: 5488131Abstract: A method for synthesizing enantiomerically enriched chemical intermediates with predetermined chirality is described. The method comprises formation of a pseudoephedrine amide, followed by stereoselective alkylation at the alpha carbon. The chiral auxiliary can then be cleaved off, affording chiral end products useful for further transformations. The enantiomeric enrichment of the chiral end products may exceed 98%, and the chiral auxiliary can be recovered. Novel amides of pseudoephedrine used in this method are also disclosed.Type: GrantFiled: March 23, 1994Date of Patent: January 30, 1996Assignee: California Institute of TechnologyInventor: Andrew G. Myers
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Patent number: 5432262Abstract: Mixture containing .alpha.-L-aspartyl-L-phenylalanine methyl ester and 3-benzyl-6-carboxymethyl-2,5-dioxopiperazine are brought into contact with hydrochloric acid in an aqueous solvent to precipitate .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride and 3-benzyl-6-carboxymethyl-2,5-dioxopiperazine, which are then separated from each other by classification.Type: GrantFiled: January 12, 1993Date of Patent: July 11, 1995Assignee: Ajinomoto Co., Inc.Inventors: Tadashi Takemoto, Katsumi Sugiyama
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Patent number: 5425787Abstract: The problems in crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl ester, namely, problems in crystal slurry properties in solid-liquid separation, scaling at heat transfer surfaces, and the like, are solved by a method for crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl ester which comprises cooling a solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester by indirect heat exchange with a coolant while stirring, wherein the solution is cooled by circulating a coolant while continuously adding an aqueous solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester dropwise to a crystallizing solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester having a temperature difference of not greater than 20.degree. C. from the coolant, thereby to keep a temperature difference of not greater than 20.degree. C. between the coolant and the crystallizing solution.Type: GrantFiled: February 28, 1994Date of Patent: June 20, 1995Assignee: Ajinomoto Co., Inc.Inventors: Sou Abe, Shinichi Kishimoto
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Patent number: 5424477Abstract: .alpha.-L-Aspartyl-L-phenylalanine methyl ester (.alpha.-APM) is prepared by catalytic hydrogenation of N-benzyloxycarbonyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester (Z-.alpha.-APM). The catalytic hydrogenation is conducted in an aqueous suspension containing the Z-.alpha.-APM in the form of particles whose average particle size is not greater than 800 .mu.m. The starting Z-.alpha.-APM may contain up to 30 wt. % of its .beta.-isomer provided that the process additionally includes recrystallization of the .alpha.-APM, collection of the .alpha.-APM by filtration and recycling of the filtrate for use in the aqueous suspension of Z-.alpha.-APM.Type: GrantFiled: September 30, 1993Date of Patent: June 13, 1995Assignee: Mitsui Toatsu Chemicals IncorporatedInventors: Chojiro Higuchi, Ikumi Kitada, Akinori Nagatomo, Katashi Enomoto, Masanobu Ajioka, Akihiro Yamaguchi
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Patent number: 5395827Abstract: The present invention pertains to antagonists of excitatory amino acid neurotransmitter receptor antagonists, their method of preparation as well as compositions containing them which have the general formula: ##STR1## wherein n and m independently are 0, 1, 2, or 3; R.sub.1 is selected from the group consisting of hydrogen and R.sub.2 ; R.sub.2 is selected from the group consisting of hydrogen, halogen, halomethyl, nitro, amino, alkoxy, hydroxyl, hydroxymethyl, C.sub.1 to C.sub.6 lower alkyl, C.sub.7 to C.sub.12 higher alkyl, aryl and aralkyl, wherein if R.sub.2 is hydrogen, R.sub.1 is not hydrogen; R.sub.3 is selected from the group consisting of hydrogen and C.sub.1 to C.sub.6 lower alkyl; the stereoisomers thereof in their resolved or racemic form, and pharmaceutically acceptable salts thereof.Type: GrantFiled: December 22, 1993Date of Patent: March 7, 1995Assignee: Guilford Pharmaceuticals Inc.Inventors: Waclaw J. Rzeszotarski, Suzanne R. Ellenberger, Maria E. Guzewska, John W. Ferkany, Gregory S. Hamilton, Raymond J. Patch, Edward W. Karbon, Jr
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Patent number: 5374765Abstract: Disclosed is a method for extracting an amino acid ester from a hydrous solution which comprises adding thereto a water-insoluble organic solvent and then an amount of a base effective to liberate only a portion of the amino acid ester in free base form, and transferring the thus liberated amino acid ester in the free base form into the organic layer, and repeating the neutralization-extraction steps until all of the amino acid ester has been extracted.Type: GrantFiled: January 19, 1993Date of Patent: December 20, 1994Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Tomoko Kamashita, Hiroyuki Yamashita, Teruyuki Nagata, Masanobu Ajioka
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Patent number: 5359124Abstract: New .beta.-phenylisoserine derivative of formula (I), its preparation and its use as intermediate in the synthesis of taxol or of its derivatives.Type: GrantFiled: August 21, 1992Date of Patent: October 25, 1994Inventors: Jean-Pierre Duchesne, Michel Mulhauser
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Patent number: 5359128Abstract: The invention comprises compositions and methods for the treatment of psoriasis.Type: GrantFiled: February 11, 1993Date of Patent: October 25, 1994Inventor: Izhak Blank
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Patent number: 5354884Abstract: .alpha.-Fluoro-substituted N-acryloylamino acid derivatives of the formula ##STR1## are used to make polymers optionally for chromatographic resolution of racemates into their enantiomers. The fluorine atom improves performance in many instances.Type: GrantFiled: October 1, 1992Date of Patent: October 11, 1994Assignee: Bayer AktiengesellschaftInventors: Rolf Grosser, Walter Lange, Bruno Bomer, Dieter Arlt, Dietmar Bielefeldt
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Patent number: 5350681Abstract: The present invention discloses a method for the enzymatic synthesis of a peptide. A protected peptide having a C-terminal carboxylate group or a protected, N-acyl amino acid having an alpha carboxylate group is reacted with a protected peptide having an N-terminal ammonium group or a protected amino acid having an alpha ammonium group in the presence of a condensation enzyme under conditions in which the carboxylate group and the ammonium group condense to form a protected, uncharged, peptide product. This peptide product is transported across a water-immiscible hydrophobic phase into an aqueous product phase and prevented from back diffusing across the water-immiscible hydrophobic phase. The peptide product can be converted, chemically or enzymatically, to a charged species that cannot back diffuse across the water-immiscible phase into the aqueous reaction phase.Type: GrantFiled: August 12, 1992Date of Patent: September 27, 1994Assignee: The Coca-Cola CompanyInventors: Guillermo A. Iacobucci, Daniel J. Brose, Roderick J. Ray, Paul van Eikeren
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Patent number: 5336800Abstract: Oxamides useful as dye intermediates have the formula ##STR1## where R.sup.1 and R.sup.2 are independently of each other hydrogen, C.sub.1 -C.sub.4 -alkyl or phenyl,X is hydroxyl, nitro or a radical of the formula --NR.sup.3 R.sup.4, where R.sup.3 is hydrogen or C.sub.1 -C.sub.4 -alkanoyl and R.sup.4 is hydrogen, C.sub.1 -C.sub.4 -alkyl or phenyl,Z is C.sub.2 -C.sub.8 -alkylene, substituted or unsubstituted phenylene or substituted or unsubstituted naphthylene, or X--Z and R.sup.1 are, together with the nitrogen atom joining them together, the radical of the formula ##STR2## where R.sup.3 is as defined above,L is a bridge member andY is vinyl or a radical of the formula --C.sub.2 H.sub.4 --A, where A is hydroxyl or a group which is detachable under alkaline reaction conditions.Type: GrantFiled: January 4, 1993Date of Patent: August 9, 1994Assignee: BASF AktiengesellschaftInventors: Bernd Siegel, Manfred Patsch, Knut Kessel
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Patent number: 5336805Abstract: Process for preparing an a-amino acid having the general formula (1) of ##STR1## where R represents an aryl group or a substituted aryl, cycloalkyl or alkyl group, in which process glyoxylic acid, or a precursor or derivative thereof, is contacted in the presence of sulphamic acid with an unsaturated compound chosen from the group of aromatics, cycloalkenes and alkenes. By applying the process higher efficiencies are obtained.The acid obtained as reaction product can be esterified and amidated without prior isolation.Type: GrantFiled: August 12, 1992Date of Patent: August 9, 1994Assignee: DSM N.V.Inventors: Wilhelmus H. J. Boesten, Nicolaas A. de Heij
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Patent number: 5324747Abstract: Compounds of the formula ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, n, m, o, p and q are as hereinafter set forth, and, when R.sub.2 is hydrogen, pharmaceutically acceptable salts thereof with bases, are described. The compounds of formula 1 are potent inhibitors of phospholipases A.sub.2 (PLA.sub.2 's) and are therefore useful in the treatment of inflammatory diseases, such as psosiasis, inflammatory bowel disease, asthma, allergy, arthritis, dermatitis, gout, pulmonary disease, myocardial ischemia/reperfusion, and trauma induced inflammation, such as spinal cord injury.Type: GrantFiled: July 15, 1992Date of Patent: June 28, 1994Assignee: Hoffmann-La Roche Inc.Inventors: Mathew Carson, Ru-Jen L. Han, Ronald A. LeMahieu, Vincent S. Madison
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Patent number: 5317077Abstract: Bioerodible polyarylates derived from biocompatible dicarboxylic acids and natural amino acid-derived diphenol starting materials. Molded articles and controlled drug delivery systems prepared from the polyarylates are also disclosed.Type: GrantFiled: March 29, 1993Date of Patent: May 31, 1994Assignee: Rutgers, The State University of New JerseyInventors: Joachim B. Kohn, James J. Fiordeliso
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Patent number: 5312826Abstract: Disclosed are a dicarboxylic acid compound represented by the formula (I): ##STR1## wherein R represents hydrogen atom, a lower alkyl group, phenyl group or hydroxyl group; R.sup.1 represents a straight or branched alkyl group having 1 to 10 carbon atoms or a lower alkyl group substituted by a group selected from aryl group, a sulfur- or nitrogen-containing heterocyclic monocyclic group and a cycloalkyl group having 4 to 8 carbon atoms; R.sup.2 represents a substituted or unsubstituted aryl group, a cycloalkyl group having 4 to 8 carbon atoms or a sulfur-containing or nitrogen-containing heterocylcic group; X represents sulfur atom, oxygen atom or a substituted or unsubstituted imino group; Y.sup.1 represents imino group, oxygen atom or sulfur atom and Y.sup.2 represents nitrogen atom, or Y.sup.1 represents a vinylene group and Y.sup.2 represents a group: --CH.dbd.Type: GrantFiled: June 19, 1992Date of Patent: May 17, 1994Assignee: Tanabe Seiyaku Co., Ltd.Inventors: Ken-ichi Nunami, Tameo Iwasaki, Kazuo Matsumoto, Koji Yano, Isao Yamaguchi
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Patent number: 5298648Abstract: Aspartame, crystallized in the presence of a crystal growth inhibitor comprising one or more of dipeptides, amino acids, saccharides, organic acids and inorganic salts, has a thick and firm crystal habit. The crystals may be easily separated by solid-liquid separation, and the drying load of them is low. After being dried, the dried aspartame powder may be handled with ease and it has excellent powdery characteristics.Type: GrantFiled: April 30, 1992Date of Patent: March 29, 1994Assignee: Ajinomoto Co., Inc.Inventors: Kazuyoshi Ebisawa, Rie Kawaoka, Nobuya Nagashima, Satoshi Kumon
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Patent number: 5294714Abstract: A method of preparing .alpha.-APM derivatives without using an expensive L-phenylalanine is provided, wherein 2,5-dioxopiperazine-3-acetamide is reacted with acetic anhydride to give N,N'-diacetyl-6-cyanomethyl-2,5-dioxopiperazine, which is then reacted with benzaldehyde in the presence of a strong base to give 1-acetyl-3-benzylidene-6-cyanomethyl-2,5-dioxopiperazine. This is treated with hydrazine to give 3-benzylidene-6-cyanomethyl-2,5-dioxopiperazine, which is then reduced to prepare 3-benzyl-6-cyanomethyl-2,5-dioxopiperazine, which is converted by reaction with methanol in the presence of a strong acid to an .alpha.-APM derivative for use as a sweetener.Type: GrantFiled: October 23, 1992Date of Patent: March 15, 1994Assignee: Ajinomoto Co., Inc.Inventors: Tadashi Takemoto, Ryoichiro Nakamura
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Patent number: 5292923Abstract: A method of preparing .varies.-L-aspartyl-L-phenylalanine methyl ester hydrochloride (.varies.-APM.HCL) from a reaction mixture of N-formyl-L-aspartic acid anhydride and L-phenylalanine methyl ester (PM), wherein .alpha.-APM.HCl is produced without isolating an intermediate by solid-liquid separation during the course of the reaction process.Type: GrantFiled: May 21, 1992Date of Patent: March 8, 1994Assignee: Ajinomoto Co., Inc.Inventors: Toshihisa Kato, Shinichi Kishimoto, Hideo Takeda, Mikiya Kano, Tadashi Takemoto
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Patent number: 5292924Abstract: .alpha.-Fluoro-substituted N-acryloylamino acid derivatives of the formula ##STR1## are used to make polymers optionally for chromatographic resolution of racemates into their enantiomers. The fluorine atom improves performance in many instances.Type: GrantFiled: November 13, 1992Date of Patent: March 8, 1994Assignee: Bayer AktiengesellschaftInventors: Rolf Grosser, Walter Lange, Bruno Bomer, Dieter Arlt, Dietmar Bielefeldt
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Patent number: 5288898Abstract: As new compounds are now provided N-methyl-3-(3,4-dihydroxyphenyl)serine alkyl esters which are effective as an .alpha.-adrenergic and .beta.-adrenergic agent to stimulate the .alpha.-adrenergic and .beta.-adrenergic functions of the central nervous system of mammalian animals and are expectable to be useful for therapeutic treatment of disorders as invoked by reduced biological activities or functions of the .alpha.- and/or .beta.-adrenergic neurons. N-methyl-L-threo-3-(3,4-dihydroxyphenyl)serine (C.sub.1 -C.sub.6) alkyl esters are preferred amongst the new compounds of this invention.Type: GrantFiled: May 4, 1993Date of Patent: February 22, 1994Assignee: Zaidan Hojim Biseibutsu Kagaku Kenkyu KaiInventors: Hamao Umezawa, Toshiharu Nagatsu, Tomio Takeuchi, Hajime Morishima, Yoshio Sawasaki, Hiroshi Takezawa, Fujinori Sasaki
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Patent number: 5274167Abstract: An optically active N-(meth)acryloyl amino acid amide of the formula ##STR1## in which R is hydrogen or methyl,R.sub.1 represents an optionally substituted alkyl, cycloalkyl, aralkyl, aryl or heteroaryl radical,R.sub.3 represents hydrogen or denotes together with R.sub.1 a tri- or tetramethylene group;X denotes oxygen or a NR.sub.4 -group wherein R.sub.4 represents hydrogen or alkyl or denotes together with R.sub.2 and the nitrogen atom a 5- to 7-membered ring which ring is optionally substituted by the group COO-alkyl (1-6 carbon atoms) or by one or two alkyl radicals (1-4 carbon atoms) andR.sub.2 denotes a strongly space-filling hydrocarbon radical.The amide is polymerized and optionally bound to a support such as silica, and can then be used for the chromatographic separation of racemic mixtures of pharmacologically active compounds.Type: GrantFiled: February 13, 1992Date of Patent: December 28, 1993Assignee: Bayer AktiengesellschaftInventors: Walter Lange, Bruno Bomer, Rolf Grosser, Dieter Arlt
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Patent number: 5266719Abstract: In neutralizing an acid addition salt of .alpha.-APM in an aqueous medium, the .alpha.-APM concentration in the neutralized liquid is controlled to fall within the range of from 3 to 10 wt. % at the finish of neutralization. Then, the liquid is heated to 50.degree. to 80.degree. C. and neutralization is effected with stirring to the isoelectric point of .alpha.-APM; or after the neutralization, the neutralized liquid is heated. The neutralized liquid is thereafter cooled with or without stirring so that crystals of .alpha.-APM are precipitated.Type: GrantFiled: May 20, 1992Date of Patent: November 30, 1993Assignee: Ajinomoto Co., Inc.Inventors: Shinichi Kishimoto, Kimiyasu Sakamoto, So Abe, Toshihisa Kato
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Patent number: 5256806Abstract: Novel intermediates useful in the preparation of the optically active antiviral compound [1R-(1.alpha.,2.beta.,3.alpha.)]-2-amino-9-[2,3-bis(hydroxymethyl)cyclobut yl]-1,9-dihydro-6H-purin-6-one are described.Type: GrantFiled: November 12, 1992Date of Patent: October 26, 1993Assignee: E. R. Squibb & Sons, Inc.Inventors: Gregory S. Bisacchi, Toomas Mitt
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Patent number: 5246943Abstract: This invention relates to novel substituted 1,2,3,4-tetrahydroisoquinolines which are useful in the treatment of vascular restenosis, various disorders of the central nervous system, in the regulation of female reproductive functions, in cognitive enhancement, in atherosclerosis and in treating excessive AVP secretory disorders. Novel intermediates useful in the preparation of the compounds are also disclosed. Methods of using the compounds and pharmaceutical compositions containing them are disclosed.Type: GrantFiled: May 19, 1992Date of Patent: September 21, 1993Assignee: Warner-Lambert CompanyInventors: Clifton J. Blankley, John C. Hodges, Sylvester Klutchko
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Patent number: 5216115Abstract: Bioerodible polyarylates derived from biocompatible dicarboxylic acids and natural amino acid-derived diphenol starting materials. Molded articles and controlled drug delivery systems prepared from the polyarylates are also disclosed.Type: GrantFiled: August 13, 1992Date of Patent: June 1, 1993Assignee: Rutgers, The State University of New JerseyInventors: Joachim B. Kohn, James J. Fiordeliso
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Patent number: 5198548Abstract: A process for the preparation of D(-) and L(+)-3,3-diphenylalanine and D(-) and L(+)-substituted 3,3-diphenylalanines is described where N-protected DL-3,3-diphenylalanine or N-protected-DL-substituted 3,3-diphenylalanine are treated with (-)cinchonidine and the resulting salt resolved into the desired enantiomers, as well as derivatives thereof and valuable intermediates used in the process.Type: GrantFiled: January 30, 1992Date of Patent: March 30, 1993Assignee: Warner-Lambert CompanyInventors: Vladimir Beylin, Huai G. Chen, Om P. Goel, John G. Topliss
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Patent number: 5198583Abstract: The optically active antiviral compound [1R-(1.alpha., 2.beta., 3.alpha.)]-2-amino-9-[2,3-bis(hydroxymethyl)-cyclobutyl]-1,9-dihydro-6H-pu rin-6-one and novel intermediates useful in its preparation are described.Type: GrantFiled: October 3, 1991Date of Patent: March 30, 1993Assignee: E. R. Squibb & Sons, Inc.Inventors: Gregory S. Bisacchi, Toomas Mitt
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Patent number: 5175153Abstract: The present invention is novel substituted .alpha.-amino acids, pharmaceutical compositions, method of use, and preparations therefore having utility for treating disorders which benefit from blockade of aspartate and glutamate receptors.Type: GrantFiled: October 14, 1988Date of Patent: December 29, 1992Assignee: Warner-Lambert CompanyInventors: Christopher F. Bigge, James T. Drummond, Vlad E. Gregor, Graham Johnson, Michael R. Pavia
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Patent number: 5144073Abstract: Disclosed is a process for synthesis of a dipeptide such as N-acetyl-L-.alpha.-aspartyl-L-phenylalanine methyl ester wherein one amino acid serves as a chiral template which allows for synthesis of a second amino acid residue to form said dipeptide. The process involves several novel steps such as a nucleophile addition step. In addition, several novel intermediates are described.Type: GrantFiled: September 14, 1989Date of Patent: September 1, 1992Inventor: John C. Hubbs
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Patent number: 5130472Abstract: The present invention relates to a new process for the preparation of Erbstatin and Erbstatin analogs, which can be represented by the following formula (I) ##STR1## wherein R is hydrogen, a lower alkyl or a lower alkanoyl group;n is an integer of 1 to 3;A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --;R.sub.1 is hydrogen or a lower alkyl group, andR.sub.2 is a hydrogen or halogen atom.Type: GrantFiled: November 2, 1990Date of Patent: July 14, 1992Assignee: Farmitalia Carlo Erba S.r.l.Inventors: Franco Buzzetti, Angelo Crugnola, Paolo Lombardi
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Patent number: 5113009Abstract: A cyclical process for producing and isolating a mineral acid salt of an amino acid methyl ester in high purity and yield from the reaction solution produced by esterifying an amino acid with methanol in methanol in the presence of a mineral acid, by cooling the resulting reaction solution to precipitate crystals of the mineral acid salt; filtering the crystals;drying the isolated wet crystals or washing with another organic solvent; and recycling the filtrate for reuse in the esterification reaction.Type: GrantFiled: December 26, 1989Date of Patent: May 12, 1992Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Masanobu Ajioka, Chojiro Higuchi, Takeshi Oura, Toshio Katoh, Akihiro Yamaguchi
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Patent number: 5100654Abstract: A phosphorylated derivative of L-dopa of the formula ##STR1## wherein when X is ##STR2## wherein Z is --CH.sub.2, N, S or a linkage other than oxygen which renders the phosphate group resistant to hydrolysis by phosphatase enzymes in tissues and biological fluids,then Y is OQ, wherein Q is H or an alkyl with one to twelve carbon atoms, orwherein X is OQ, then Y is ##STR3## wherein R' is hydrogen or a pharmaceutically acceptable cation and R is a moiety which increases hydropobicity. The phosphorylated derivative of L-dopa is useful as an agent to increase the melanin content in mammalian skin and hair.Type: GrantFiled: April 7, 1989Date of Patent: March 31, 1992Assignee: Yale UniversityInventors: John M. Pawelek, Michael P. Osber
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Patent number: 5099060Abstract: Novel amino acid-derived polycarbonates and amino acid-derived diphenol compound starting materials from which the polycarbonates are polymerized. Polymer blends of the amino acid-derived polycarbonates with polyiminocarbonates prepared from identical amino acid-derived diphenol starting materials.Type: GrantFiled: June 12, 1990Date of Patent: March 24, 1992Assignee: Rutgers, The State University of New JerseyInventors: Joachim B. Kohn, Satish K. K. Pulapura
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Patent number: 5093478Abstract: In the esterification of glutathione with alcohol in the presence of acid catalyst, neutral glutathione monoester is isolated in high yields without the intermedite isolation of ester acid salt by treating the reaction mixture with base anion exchange resin (basic form) to neutralize the acid and bind the resulting acid anion and unesterified glutatione. Dehydrating agent is used to drive the reaction toward esterification. In the production of glutathione monester acid salts a soluble dehydrating agent is advantageously used.Type: GrantFiled: July 14, 1989Date of Patent: March 3, 1992Assignee: Cornell Research Foundation, Inc.Inventors: Owen W. Griffith, Ernest B. Campbell
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Patent number: 5064961Abstract: A process for the preparation of the optically active compound [IR-(1.alpha., 2.beta., 3.alpha.)]-2-amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one, represented by the formula: ##STR1## and novel intermediates are described.Type: GrantFiled: December 18, 1989Date of Patent: November 12, 1991Assignee: E. R. Squibb & Sons, Inc.Inventors: Gregory S. Bisacchi, Toomas Mitt
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Patent number: 5055399Abstract: Enzyme-catalyzed synthetic reactions having otherwise unfavorable equilibria are facilitated by recovery of polypeptides by electrodialysis. A process of preparing polypeptides is provided that can be operated continuously to produce high yields of enriched polypeptides without recourse to post-synthetic product manipulations heretofore employed that are expensive and present a risk of residual toxic by-products. The invention is applied to advantage in the preparation of alpha-L-aspartyl-L-phenylalanine lower alkyl esters.Type: GrantFiled: May 4, 1989Date of Patent: October 8, 1991Assignee: Genentech, Inc.Inventors: Bradley R. Snedecor, Chung C. Hsu
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Patent number: 5055588Abstract: A process for preparing N-substituted amino acid esters having the formula (I): ##STR1## wherein R.sub.1 and R.sub.4, the same or different, are an alkyl, aralkyl, cycloalkyl or aryl group; and R.sub.2 and R.sub.3, the same or different,are an alkyl, aralkyl, aryl, heterocycle-alkyl, aminoalkyl or guanidylalkyl, by the reaction of .alpha.-amino acid esters with .alpha.-substituted carboxylic acid esters, under the condition of substantially free from solvent, which can afford their optical isomers in a good yield.Type: GrantFiled: May 9, 1990Date of Patent: October 8, 1991Assignee: Daicel Chemical Industries Ltd.Inventors: Ichirou Takase, Kazuo Sato, Noritsugu Yamasaki, Yukihisa Goto
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Patent number: RE34878Abstract: A compound of D-phenylalanine derivative for hypoglycemic use, represented by the general formula ##STR1## R.sup.1 is selected from hydrogen, alkyl of 1 to 5 carbon atoms, aryl of 6 to 12 carbon atoms, aralkyl of 6 to 12 carbon atoms, ##STR2## --CH.sub.2 CO.sub.2 R.sup.3, --CH(CH.sub.3)--OCO--R.sup.3, and --CH.sub.2 --OCO--C(CH.sub.3).sub.3 ; R.sup.2 is selected from groups comprising aryl of 6 to 12 carbon atoms, a hetero six-membered ring, a hetero five-membered ring, cycloalkyl, or cycloalkenyl, any of which groups may have one or more substituents; and R.sup.3 is selected from hydrogen and alkyl of 1 to 5 carbon atoms; the salts thereof, and precursors which can be converted thereto in the human or animal body.Some of the compounds are novel per se.Type: GrantFiled: November 23, 1993Date of Patent: March 14, 1995Assignee: Ajinomoto Co., Inc.Inventors: Shigeshi Toyoshima, Yoshiko Seto, Hisashi Shinkai, Koji Toi, Izumi Kamashiro