Amide In Acid Moiety Patents (Class 560/41)
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Patent number: 5627302Abstract: The invention relates to novel asymmetrically substituted diaminodicarboxylic acid derivatives of the formula ##STR1##Type: GrantFiled: April 24, 1996Date of Patent: May 6, 1997Assignee: Hafslund Nycomed Pharma AktiengesellschaftInventors: Johann Hiebl, Franz Rovenszky
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Patent number: 5623079Abstract: The present invention provides an industrial method of producing N-formyl-L-aspartic anhydride from N-formyl-L-aspartic acid, formic acid and acetic anhydride with less residual formic acid than conventional methods.Type: GrantFiled: September 28, 1995Date of Patent: April 22, 1997Assignee: Ajinomoto Co., Inc.Inventors: Takehiko Kataoka, Shinichi Kishimoto, Osahiro Sato
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Patent number: 5621137Abstract: A method for dissolving crystalline L-alpha-aspartyl-L-phenyl-alanine methyl ester product is disclosed. The product is obtained by crystallizing the ester from an aqueous solution, by cooling. The initial concentration of ester in the aqueous solution used provides at least 10 grams of precipitated solid phase per liter of solution. The solution is cooled through conductive heat transfer without effecting forced flow to form a sherbet-like pseudo solid phase.Type: GrantFiled: June 5, 1995Date of Patent: April 15, 1997Assignee: Ajinomoto Co., Inc.Inventors: Masayoshi Naruse, Haruo Kawasaki, Shinichi Kishimoto, Harutoshi Oura, Masao Nakamura, Hideo Takeda
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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: 5599954Abstract: Compounds represented by the following general structural formula (1) and methods for producing the compounds: ##STR1## R.sup.1 represents a group such as benzyloxycarbonyl, R.sup.2 represents a lower alkyl group, R.sup.3 represents a hydrogen atom or a protecting group, each of M.sup.1 and M.sup.2 represents a metal atom, and n represents the atomic valence of M.sup.1. Intermediates for HMG-CoA reductase inhibitors can be prepared safely and easily from these compounds.Type: GrantFiled: January 26, 1996Date of Patent: February 4, 1997Assignee: Takasago International CorporationInventors: Sigeru Mitsuhashi, Tsukasa Sotoguchi, Yoshifumi Yuasa, Hidenori Kumobayashi
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Patent number: 5599947Abstract: Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof.These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure ##STR1## in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L--Ala, L--Ile, L--Phe, L--Trp, L--Thr or an amide such as NHCH.sub.2 C.sub.6 H.sub.5 or NH(CH.sub.2).sub.2 C.sub.6 H.sub.Type: GrantFiled: March 24, 1995Date of Patent: February 4, 1997Assignee: G. D. Searle & Co.Inventors: Sean T. Nugent, Richard A. Mueller
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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: 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: 5563278Abstract: This invention provides novel phenyl and heterocyclic derivatives, their pharmaceutical formulations and their use for antagonizing angiotensin II receptors in mammals.Type: GrantFiled: May 30, 1995Date of Patent: October 8, 1996Assignee: Eli Lilly and CompanyInventors: Sherryl L. Lifer, Winston S. Marshall, Fariborz Mohamadi, Jon K. Reel, Richard L. Simon, Mitchell I. Steinberg, Celia A. Whitesitt
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Patent number: 5559268Abstract: A process for the preparation of N-substituted dehydroamino acid esters by contacting a .beta.-hydroxy-.alpha.-amino acid ester or N- or O-substituted .beta.-hydroxy-.alpha.-amino acid ester with an excess of acetic anhydride and a base is disclosed.Type: GrantFiled: November 17, 1994Date of Patent: September 24, 1996Assignee: E. I. Du Pont de Nemours and CompanyInventor: William A. Nugent
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Patent number: 5559267Abstract: Chiral 1,4-diol cyclic sulfates and their use as precursors in the preparation of chiral phospholane ligands, and chiral complexes useful as catalysts for carrying out enantioselective reactions.Type: GrantFiled: May 24, 1995Date of Patent: September 24, 1996Assignee: E. I. Du Pont de Nemours and CompanyInventor: Mark J. Burk
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Patent number: 5543423Abstract: The present invention relates to compounds that can maintain, increase, or restore sensitivity of cells to therapeutic or prophylactic agents. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well-suited for treatment of multi-drug resistant cells, for prevention of the development of multi-drug resistance, and for use in multi-drug resistant cancer therapy.Type: GrantFiled: January 23, 1995Date of Patent: August 6, 1996Assignee: Vertex Pharmaceuticals, IncorporatedInventors: Robert E. Zelle, Matthew W. Harding
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Patent number: 5543554Abstract: A process for obtaining dry crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester having a water content of about 2 wt. % to about 6 wt. % based on the weight of the wet crystals is disclosed. This process comprises exposing wet crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester, having a water content not greater than 50 wt. % based on the weight of the wet crystals and obtained by the crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl ester from an unagitated solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester, to a flow of air having a temperature of 80.degree. C. to 200.degree. C.Type: GrantFiled: February 28, 1995Date of Patent: August 6, 1996Assignee: Ajinomoto Co., Inc.Inventors: Harutoshi Ohura, Akihiko Yasaki, Shinichi Kishimoto, Masayoshi Naruse
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Patent number: 5532015Abstract: A process for quickly and reproducibly obtaining .alpha.-L-aspartyl-L-phenylalanine methyl ester with controlled water content is disclosed. Wet crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester obtained by crystallization are subjected to a drying step to adjust the water content to not more than 5 wt %, and subsequently a gas adjusted to a temperature of 20-80.degree. C. and relative humidity of 20-90 RH % is contacted with the dried crystals to control water content.Type: GrantFiled: November 21, 1994Date of Patent: July 2, 1996Assignee: Ajinomoto Co., Inc.Inventors: Atsuhiko Hirano, Satoshi Yamahara, Takehiko Kataoka, Shinichi Kishimoto
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Patent number: 5530155Abstract: Addition of a reaction mixture obtained by the mineral acid hydrolysis of at least one side flow generated from the production of .alpha.-L-aspartyl-L-phenylalanine methyl ester to a crystallization slurry containing L-phenylalanine while maintaining the pH of the slurry at 3-8 by adding aqueous alkali affords crystallized L-phenylalanine having a low water content in a high yield.Type: GrantFiled: March 24, 1995Date of Patent: June 25, 1996Assignee: Ajinomoto Co., Inc.Inventors: Toyoto Hijiya, Chiaki Mochizuki, Tadashi Takemoto, Kazutaka Nagashima
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Patent number: 5527689Abstract: The invention relates to a process for the preparation of N-benzyloxycarbonyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester by enzymatic coupling of N-benzyloxycarbonyl-L-aspartic acid and L-phenylalanine methyl ester in an aqueous medium with formation of a precipitate, the coupling reaction being effected with (virtually) equimolar quantities of N-benzyloxycarbonyl-L-aspartic acid and L-phenylalanine methyl ester under the influence of a neutral protease at an initial pH of from 4.5 to 6.0 and in the presence of from 3 to 25%, calculated as per cent by weight based on the total reaction mixture, of an alkali metal salt, alkaline earth metal salt or ammonium salt.Type: GrantFiled: December 29, 1994Date of Patent: June 18, 1996Assignee: Holland Sweetener Company V.o.F.Inventors: Shigeaki Irino, Shin-ichiro Nakamura, Kiyotaka Oyama, Peter J. L. M. Quaedflieg, Theodorus J. G. M. Van Dooren
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Patent number: 5523434Abstract: The synthesis of phenol sulfonate esters of alkanoyl amino acids is conducted in the presence of aqueous base to provide bleach activator compounds. Thus, the acid chloride of N-nonanoyl-6-aminocaproic acid is reacted with the sodium salt of p-phenol sulfonate in the presence of water at a pH in the range of about 9 to about 12 to yield the corresponding phenol sulfonate ester. The synthesis of the phenol sulfonate ester of the monononyl amide of adipic acid is also illustrated.Type: GrantFiled: March 15, 1995Date of Patent: June 4, 1996Assignee: The Procter & Gamble CompanyInventors: Michael E. Burns, Anthony J. Simpson
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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: 5514794Abstract: Derivatized drugs are prepared with a linker consisting of a malonate, wherein the drug is linked through a methylene to the 2-position carbon of the malonate.Type: GrantFiled: January 22, 1991Date of Patent: May 7, 1996Assignee: Eli Lilly and CompanyInventor: Russell L. Barton
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Patent number: 5510508Abstract: A method of preparing N- N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl!-L-phenylalanine 1-methyl ester of the formula ##STR1## useful as a sweetening agent, wherein an aqueous-alcoholic solution of aspartame and 3,3-dimethylbutyraldehyde of pH 4.5-5 is treated, at room temperature, with hydrogen at a pressure less than or equal to 1 bar, in the presence of a catalyst selected from the group comprising platinum or palladium on activated carbon or in the form of platinum or palladium black, and wherein the product formed is purified by precipitation and filtration after removal of the alcohol part of the solvent under vacuum.Type: GrantFiled: May 8, 1995Date of Patent: April 23, 1996Inventors: Nofre Claude, Jean-Marie Tinti
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Patent number: 5510507Abstract: A process and catalyst composition are provided for the highly efficient enantioselective hydrogenation of dehydroamino acid derivatives. The catalyst composition comprises rhodium or iridium and a diphosphinite carbohydrate ligand, wherein the phosphorous atoms are attached to aromatic groups substituted with electron-donating substituents. Also provided is a means to selectively produce .alpha. amino acids in either the L or the D form, based upon use of a sugar in the ligand with phosphinites attached in an absolute Right-Left or Left-Right configuration, respectively.Type: GrantFiled: April 24, 1995Date of Patent: April 23, 1996Assignee: E. I. Du Pont de Nemours and CompanyInventors: Timothy A. Ayers, Thaliyil V. Rajanbabu
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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: 5502238Abstract: The invention relates to a process for the crystallisation of aspartame by neutralising an aqueous solution of aspartame, having a pH of less than 3, with a base and homogenising the solution by means of forced convection, characterised in that the solution is neutralised, and homogenised, in such a manner that the solution obtained is substantially homogeneous and has a pH higher than 3, with the solution no longer being mechanically stirred at least from the beginning of the last second before crystallisation is visually perceptible.Type: GrantFiled: March 1, 1995Date of Patent: March 26, 1996Assignee: Holland Sweetener Company V.o.F.Inventors: Marinus P. W. M. Rijkers, Alexander P. M. Vrinzen
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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: 5495047Abstract: Fused tricyclic compounds of formula (I) as disclosed herein, and salts and prodrugs thereof, are tachykinin antagonists, useful for treating pain.Type: GrantFiled: April 21, 1994Date of Patent: February 27, 1996Assignee: Merck, Sharp & Dohme (Ltd.)Inventors: Monique B. Van Niel, Brian J. Williams, Walfred S. Saari
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One-pot process for the preparation of .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride
Patent number: 5476961Abstract: A one-pot process for the preparation of .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride is disclosed (.alpha.-APM(HCl)). .alpha.-APM(HCl) is an intermediate in the preparation of aspartame.Type: GrantFiled: June 21, 1993Date of Patent: December 19, 1995Assignee: The NutraSweet CompanyInventors: John B. Hill, Yefim Gelman, Hugh L. Dryden, Jr., Robert Erickson, Kuang Hsu, Mark R. Johnson -
Patent number: 5475106Abstract: Compounds of formula: ##STR1## in which R.sub.1 represents a hydrogen atom, an alkyl or alkoxycarbonyl radical or a phenyl radical, optionally substituted,R.sub.2 represents an alkoxy, optionally substituted cycloalkyloxy, cycloalkylalkyloxy, phenylalkyloxy, polyfluoroalkyloxy or cinnamyloxy radical or a radical --NR.sub.5 R.sub.6,R.sub.3 represents a phenylamino radical in which the phenyl ring is optionally substituted, an optionally substituted phenyl radical or a naphthyl, indolyl or quinolyl radical,R.sub.4 represents a substituted phenyl radical,R.sub.5 and R.sub.6, which may be identical or different, represent a hydrogen atom or an alkyl, optionally substituted phenyl, indanyl, cycloalkylalkyl, cycloalkyl or phenylalkyl radical, or alternatively R.sub.5 and R.sub.6, together with the nitrogen atom to which they are attached, form a heterocycle, their preparation and medicinal products containing them.Type: GrantFiled: October 8, 1992Date of Patent: December 12, 1995Assignee: Rhone-Poulenc Rorer S.A.Inventors: Jean-Dominique Bourzat, Marc Capet, Claude Cotrel, Claude Guyon, Franco Manfre, Gerard Roussel
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Patent number: 5472683Abstract: This invention relates to methods of x-ray diagnostic imaging the blood pool, liver, spleen, and/or lymph system of a mammal comprising administering a contrast effective amount of a mixed carbamic anhydride as a contrast agent having the structure ##STR1## X is H, NR.sup.1 R.sup.2 or CONR.sup.1 R.sup.3, R.sup.1 is H or alkylR.sup.2 is COR.sup.3R.sup.3 is H, alkyl or arylY is NR.sup.1 R.sup.2 or CONR.sup.1 R.sup.3 andN is NR.sup.1 R.sup.4 andR.sup.4 is H, alkyl, aryl or CH(R.sup.5)CO.sub.2 R.sup.1.This invention further relates to novel mixed carbamic anhydride contrast agents having the above structure to x-ray contrast compositions comprising such agents, and to methods of x-ray diagnostic imaging utilizing such agents.Type: GrantFiled: March 9, 1995Date of Patent: December 5, 1995Assignee: Eastman Kodak CompanyInventor: Carl R. Illig
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Patent number: 5473097Abstract: Granules of .alpha.-L-aspartyl-L-phenylalanine methyl ester, containing IB crystals of the ester and having a grain size of from 100 to 1400 .mu.m have improved water solubility.Type: GrantFiled: October 1, 1993Date of Patent: December 5, 1995Assignee: Ajinomoto Company, Inc.Inventors: Shinichi Kishimoto, Akihiko Yasaki
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Patent number: 5468898Abstract: This invention relates to bicyclic aryl compounds having selective LTB.sub.4 antagonist properties and comprising an amido substituent, a substituent group having a terminal carboxylic acid or derivative thereof and a lipophilic substituent, and to methods for the treatment of disorders which result from LTB.sub.4 activity and pharmaceutical compositions including such compounds.Type: GrantFiled: April 23, 1993Date of Patent: November 21, 1995Assignee: Rhone-Poulenc Rorer Pharmaceuticals Inc.Inventors: Fu-Chih Huang, Wan K. Chan, Charles A. Sutherland, Robert A. Galemmo, Jr.
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Patent number: 5466834Abstract: A process for preparing N-acyl, N-sulfonyl and N-phosphoryl substituted isoserine esters in which a metal alkoxide is reacted with a .beta.-lactam.Type: GrantFiled: September 28, 1994Date of Patent: November 14, 1995Assignee: Florida State UniversityInventor: Robert A. Holton
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Patent number: 5466840Abstract: This invention relates to a 5 step process for preparing a purified alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate in one reaction vessel without isolation of intermediates. The steps are as follows: A) reacting an alkali metal salt of 4-hydroxybenzenesulfonic acid with a C.sub.2 to C.sub.4 carboxylic anhydride in a solvent to form an alkali metal salt of 4-acyloxybenzenesulfonic acid and a C.sub.2 to C.sub.4 carboxylic acid. B) adding an [(1-oxyalkanoyl)amino]alkanoic acid and a transesterification catalyst to the reaction product of step A) and heating at a temperature and pressure sufficient to maintain reflux of the solvent and to remove the C.sub.2 to C.sub.4 carboxylic acid from the reaction vessel to form a reaction mixture containing an alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate. C) removing the solvent from the reaction mixture formed in step B).Type: GrantFiled: August 22, 1994Date of Patent: November 14, 1995Assignee: Eastman Chemical CompanyInventors: Gary P. Lutz, George C. Zima, Rex Bernard
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Patent number: 5432178Abstract: Amidinophenol derivatives of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are (i) H, (ii) C1-4 alkyl, (iii) C1-4 alkoxy, (iv) C2-5 acyl, (v) halogen, (vi) NO.sub.2, (vii) benzoyl, (viii) COOR.sup.4 (in which R.sup.4 is C1-3 alkyl); A is bond, C1-4 alkylene, --C(R.sup.5).dbd.C(R.sup.6)-- (in which R.sup.5 and R.sup.6 are H or C1-4 alkyl; R.sup.3 is (i) CON(R.sup.7)(R.sup.8), (ii) CON(R.sup.9)--CH(R.sup.7)(R.sup.8) or (iii) ##STR2## in which ##STR3## is 4-7 membered, mono-cyclic hetero ring containing 1 or 2 N atom; R.sup.10 is H, C7-10 phenylalkyl or COOR.sup.13 (in which R.sup.13 is H, C1-4 alkyl or C7-10 phenylalkyl)); with the proviso that (i) both R.sup.7 and R.sup.8 do not represent hydrogen at the same time, and (ii) when at least one group in R.sup.7, R.sup.8 and R.sup.9 represents the group containing t-butyl ester, the other groups do not represent tile group containing carboxy; or an acid-addition salt thereof, have inhibitory activities on PLA.sub.Type: GrantFiled: September 16, 1993Date of Patent: July 11, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Hisao Nakai, Masanori Kawamura, Tsumoru Miyamoto
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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: 5420338Abstract: A method is disclosed for the production of .alpha.-APM HCl by treating an F-.alpha.-AP derivative with a mixed solvent of methanol, hydrochloric acid and water, wherein the solubility of .alpha.-APM HCl is lowered to increase the separation yield thereof.Type: GrantFiled: August 2, 1994Date of Patent: May 30, 1995Assignee: Ajinomoto Co., Inc.Inventors: Tadashi Takemoto, Shinji Fujita
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Patent number: 5420337Abstract: An enzymatic reduction method, particularly a stereoselective enzymatic reduction method, for the preparation of compounds useful as intermediates in the preparation of taxanes.Type: GrantFiled: November 12, 1992Date of Patent: May 30, 1995Assignee: E. R. Squibb & Sons, Inc.Inventors: Ramesh N. Patel, Amit Banerjee, Clyde G. McNamee, John K. Thottathil, Laszlo J. Szarka
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Patent number: 5416117Abstract: A novel cyclopropenone derivative (I) which possesses a potent inhibitory activity against thiol protease such as papain, cathepsin B, cathepsin H, cathepsin L, calpain or the like with excellent properties regarding oral absorbance, tissue transference and cell membrane permeability, and are clinically useful in the treatment of various diseases such as muscular dystrophy, amyotrophy. Also provided are a process for producing the compound (I) and a pharmaceutical composition containing the same.Type: GrantFiled: February 28, 1994Date of Patent: May 16, 1995Assignee: Mitsubishi Kasei CorporationInventors: Ryoichi Ando, Yasuhiro Morinaka, Chizuko Takahashi, Yoshikuni Tamao, Akihiro Tobe
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Patent number: 5401869Abstract: Aminomethylene compounds of the formula ##STR1## may advantageously be prepared by reacting C--H-acidic compounds of the formula ##STR2## with formamide acetals of the formula ##STR3## in which the radicals R.sup.1 to R.sup.6 have the meaning given in the description,if the process is carried out in the presence of a secondary amine of the formula ##STR4## in which R.sup.7 and R.sup.8 have the meaning given in the description.Type: GrantFiled: January 21, 1994Date of Patent: March 28, 1995Assignee: Bayer AktiengesellschaftInventors: Helmut Kraus, Nikolaus Muller, Gerhard Marzolph, Bernhard Beitzke
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Patent number: 5393915Abstract: A method for the solid-liquid separation of a suspension of .alpha.-L-aspartyl-L-phenylalanine methyl ester (.alpha.-APM) or its hydrochloride salt (.alpha.-APM.HCl), wherein an aqueous suspension of .alpha.-L-aspartyl-L-phenylalanine methyl ester or its hydrochloride salt is subjected to continuous separation by vacuum filtration.Type: GrantFiled: November 17, 1993Date of Patent: February 28, 1995Assignee: Ajinomoto Co., Inc.Inventors: Takehiko Kataoka, Akihiko Yasaki, Shinichi Kishimoto, Toshihisa Kato
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Patent number: 5391809Abstract: A method is disclosed for the production of .alpha.-APM.HCl by treating an F-.alpha.-AP derivative with a mixed solvent of methanol, hydrochloric acid and water, wherein the solubility of .alpha.-APM.HCl is lowered to increase the separation yield thereof.Type: GrantFiled: July 30, 1993Date of Patent: February 21, 1995Assignee: Ajinomoto Co., Inc.Inventors: Tadashi Takemoto, Shinji Fujita
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Patent number: 5391810Abstract: In crystallizing .alpha.-APM from a water solution or a mixed solvent solution of water and a lower alcohol in a crystallizer, the pressure in the crystallizer is held at not higher than atmospheric pressure, a water or water/alcohol mixed solution of .alpha.-APM is fed into the crystallizer with stirring so that the solvent is vaporized, and the crystallization solution is cooled and crystallized by the latent heat of vaporization or is heated so as to prevent supercooling.Type: GrantFiled: September 16, 1993Date of Patent: February 21, 1995Assignee: Ajinomoto Co., Inc.Inventors: So Abe, Shinichi Kishimoto, Toshihisa Kato, Hideo Takeda
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Patent number: 5385902Abstract: Antimicrobial compounds of the formula ##STR1## wherein A is selected from the group consisting of alkyl; phenyl; alkoxy; phenoxy; benzyloxy; monoalkylamino; dialkylamino; cyclic amino, anilino; heterocyclic; amino substituted with heterocyclic ring, methods of making and using said compounds, and compositions comprising said compounds are disclosed.Type: GrantFiled: September 1, 1993Date of Patent: January 31, 1995Assignee: Rohm and Haas CompanyInventor: Adam C. Hsu
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Patent number: 5374656Abstract: This invention relates to compounds of formula: ##STR1## in which R.sub.1 represents a hydrogen atom or an alkyl or alkoxycarbonyl radical or an unsubstituted or substituted phenyl radical,R.sub.2 represents an alkyl (1-8 C) or polyfluoroalkyl radical or an unsubstituted or substituted cycloalkyl radical,R.sub.3 represents an unsubstituted or substituted phenyl radical, a naphthyl, indolyl, quinolyl or phenylamino radical in which the phenyl ring is optionally substituted, or a quinolylamino radical, andm is 0 or 1, the process for preparing them and the medicaments containing them.Type: GrantFiled: June 25, 1992Date of Patent: December 20, 1994Assignee: Rhone-Poulenc Rorer, S.A.Inventors: Jean-Dominique Bourzat, Marc Capet, Claude Cotrel, Claude Guyon, Franco Manfre, Gerard Roussel
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Patent number: 5371269Abstract: The methyl ester of .alpha.-L-aspartyl-L-phenylalanine may be obtained in high yields directly from a reaction solution which contains N-protected- or unprotected-.alpha.-L-aspartyl-D-phenylalanine (or its methyl ester derivative), and .alpha.-L-aspartyl-L-phenylalanine methyl ester by selective crystallization of the .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride from an aqueous solution containing N-protected- or unprotected-L-aspartyl-L-phenylalanine and/or its methyl ester derivative and N-protected- or unprotected-L-aspartyl-D-phenylalanine and/or its methyl ester derivative, hydrochloric acid, and methanol, with or without stirring.Type: GrantFiled: June 22, 1993Date of Patent: December 6, 1994Assignee: Ajinomoto Co., Inc.Inventors: Kazutaka Nagashima, Satoji Takahashi
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Patent number: 5362902Abstract: Compounds of formula (I) are diuretic agents for treating various cardiovascular diseases including hypertension, heart failure and renal insufficiency.Type: GrantFiled: July 21, 1992Date of Patent: November 8, 1994Assignee: Pfizer Inc.Inventors: Ian T. Barnish, Keith James
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Patent number: 5362903Abstract: This invention is directed to provide a method for obtaining .alpha.-L-aspartyl-L-phenylalanine selectively in high yields. Diffusion dialysis with an ion exchange membrane is used to decrease hydrochloric acid concentration of a mixed solution containing hydrochloric acid and one or more of four .alpha.-L-aspartyl-L-phenylalanine derivatives, i.e., .alpha.-L-aspartyl-L-phenylalanine methyl ester, .alpha.-L-aspartyl-L-phenylalanine, .alpha.-L-aspartyl-L-phenylalanine-.beta.-methyl ester and .alpha.-L-aspartyl-L-phenylalanine dimethyl ester. The resultant solution is concentrated, to which a base is added for neutralization. Subsequently, .alpha.-L-aspartyl-L-phenylalanine is crystallized and isolated.Type: GrantFiled: November 16, 1993Date of Patent: November 8, 1994Assignee: Ajinomoto Co., Inc.Inventors: Shinji Fujita, Satoji Takahashi
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Patent number: 5359120Abstract: The invention provides compounds of the formula XX: M-Ar-CONH-R, where Ar represents an aromatic ring system, R-NH is the residue of an .alpha.-amino acid R-NH.sub.2 or oligopeptide R-NH.sub.2 and contains at least one carboxylic acid group in the form of a tertiary butyl ester and M represents a nitrogen mustard group of formula (a), where Y and L, which may be the same or different in a molecule, are leaving groups. The compounds are useful intermediates for the production of nitrogen mustard prodrugs.Type: GrantFiled: May 6, 1991Date of Patent: October 25, 1994Assignee: Cancer Research Campaign Technology LimitedInventor: Caroline J. Springer
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Patent number: 5356893Abstract: The invention provides compounds of formula (I): ##STR1## or a physiologically acceptable salt or solvate thereof wherein R.sup.1 represents a halogen or hydrogen atom or a C.sub.1-6 alkyl or C.sub.1-6 alkoxy group;R.sup.2 represents a phenyl group optionally substituted by one or two substituents;R.sup.3 represents the group ##STR2## R.sup.4 and R.sup.5, which may be the same or different, each independently represent a hydrogen atom or a halogen atom, or a group selected from hydroxy, C.sub.1-6 alkoxy or C.sub.1-6 alkyl.The compounds may be used in the treatment or prophylaxis of depression and other CNS disorders.Type: GrantFiled: September 17, 1992Date of Patent: October 18, 1994Assignee: Glaxo Group LimitedInventors: John Bradshaw, John W. Clitherow, Ian B. Campbell
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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