Amide In Acid Moiety Patents (Class 560/41)
-
Patent number: 5354892Abstract: The invention relates to biaryl substituted 4-amino-butyric acid derivatives of formula I ##STR1## wherein COX and COX' independently represent carboxyl or carboxyl derivatized in form of a pharmaceutically acceptable ester or amide; R.sub.1 represents hydrogen, lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl, aryl-lower alkyl, biaryl-lower alkyl, lower alkoxy, aryl-lower alkoxy, aryloxy, N-lower alkylamino, N,N-di-lower alkylamino, N-aryl-lower alkylamino, N,N-di-aryl-lower alkylamino, N-arylamino, N,N-diarylamino, lower alkanoylamino, aryl-lower alkanoylamino or aroylamino; R.sub.2 represents hydrogen, hydroxy, lower alkoxy, lower alkyl, aryl-lower alkyl, C.sub.3 -C.sub.Type: GrantFiled: January 25, 1993Date of Patent: October 11, 1994Assignee: Ciba-Geigy CorporationInventor: Gary Ksander
-
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
-
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
-
Patent number: 5347035Abstract: A method for crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester from a hot aqueous solution containing .alpha.-L-aspartyl-L-phenylalanine methyl ester by cooling is disclosed, which comprises (i) continuously supplying a hot aqueous solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester having a concentration such that the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is less than 0.6% by weight based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution, or if the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is 0.6% by weight or more based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution, to a crystallization vessel the temperature of which is lowered to that corresponding to the solubility of .alpha.-L-aspartyl-L-phenylalanine methyl ester or less, and (ii) continuously discharging the formed slurry from the crystallization vessel.Type: GrantFiled: September 23, 1993Date of Patent: September 13, 1994Assignee: Tosoh CorporationInventors: Hidetoshi Wakamatsu, Tsuneo Harada, Yukio Kunisawa, Kiyotaka Oyama
-
Patent number: 5347036Abstract: Novel compounds which are 2,6-di-t-butylphenols substituted on the 4 position by an anilino group, which anilino group is substituted by a carboxyl substituent, a tetrazolyl substituent or an N-methyltetrazolyl substituent, are useful antiallergic agents. Pharmaceutical compositions containing and pharmacological methods of using such compounds are also disclosed, as are synthetic intermediates for preparing such compounds. Certain of the synthetic intermediates also exhibit useful antiallergic activity.Type: GrantFiled: May 26, 1993Date of Patent: September 13, 1994Assignee: Riker Laboratories, Inc.Inventor: Robert A. Scherrer
-
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
-
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
-
Patent number: 5334746Abstract: A process for the preparation of .alpha.-L-aspartyl-L-phenylalanine methyl ester in high yield, which comprises the steps of esterifying L-phenylalanine with methanol while undergoing continuous evaporation to remove the water formed during esterification, coupling the produced L-phenylalanine methyl ester with N-formyl-L-aspartic anhydride, deformylating the produced N-formyl-L-aspartyl-L-phenylalanine methyl ester, crystallizing the formed .alpha.-L-aspartyl-L-phenylalanine methyl ester as .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloric acid salt, recovering the first .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloric acid salt, esterifying .alpha.-L-aspartyl-L-phenylalanine in the filtrate to produce the second .alpha.-L-aspartyl-L-phenylalanine methyl ester, and combining the first and second .alpha.-L-aspartyl-L-phenylalanine methyl ester product.Type: GrantFiled: December 6, 1993Date of Patent: August 2, 1994Assignee: Miwon Co., Ltd.Inventors: Kyung S. Choi, Dae K. Joo, Min S. Han, E Nam Hwang, Hong K. Choi
-
Patent number: 5328909Abstract: 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: June 25, 1992Date of Patent: July 12, 1994Assignee: Mitsubishi Kasei CorporationInventors: Ryoichi Ando, Yasuhiro Morinaka, Chizuko Takahashi, Yoshikuni Tamao, Akihiro Tobe
-
Patent number: 5326755Abstract: The present application discloses pesticidally active compounds of formula I:QQ.sup.1 CR.sup.1 .dbd.CR.sup.2 CR.sup.3 .dbd.CR.sup.4 C(.dbd.X.sup.1)NR.sup.5 R.sup.6or a salt thereof, wherein Q is an monocyclic aromatic ring, or Q is a dihalovinyl group or a group R.sup.7 --C.dbd.C-- where R.sup.7 is C.sub.1-4 alkyl, tri C.sub.1-4 alkylsilyl, halogen or hydrogen; Q.sup.1 is a 1,2-cyclopropyl ring optionally substituted by one or more groups selected from C.sub.1-3 alkyl, halo, C.sub.1-3 haloalkyl, alkynyl, or cyano; R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different with at least one being hydrogen and the others being independently selected from hydrogen, halo, C.sub.1-4 alkyl or C.sub.1-4 haloalkyl; X.sup.1 is oxygen or sulphur; R.sup.5 is C.sub.1-8 hydrocarbyl optionally substituted, halo, cyano, trifluoromethyl, trifluoromethylthio or C.sub.1-6 alkoxy; and R.sup.6 is selected from:(A) --Y.dbd.X.sup.2 --(R.sup.8).sub.a where X.sup.2 is O or S, Y is carbon, R.sup.8 is hydrogen, C.sub.Type: GrantFiled: September 10, 1992Date of Patent: July 5, 1994Assignee: Roussel UCLAFInventors: Robert J. Blade, George S. Cockerill
-
Patent number: 5324833Abstract: Compounds of the formula I, ##STR1## in which 'R.sub.1 is an amino protective group, and n stands for 1 or 2, R.sub.1 denotes hydrogen or an amino protective group, R.sub.2 denotes hydrogen or a carboxyl protective group and R.sub.3 denotes triphenylmethyl, 4-monomethoxy-trityl or 4,4'-dimethoxy-trityl, and reactive carboxylic acid derivatives of such compounds of the formula I in which R.sub.2 stands for hydrogen, are described.These compounds can be used as starting materials for the preparation of peptides. They are more suitable for this than are analogous compounds of the formula I in which R.sub.3 denotes hydrogen or one of the carbamoyl protective groups hitherto customary.Type: GrantFiled: April 13, 1990Date of Patent: June 28, 1994Assignee: Novabiochem AGInventors: Peter Sieber, Bernhard Riniker
-
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
-
Patent number: 5322964Abstract: There is disclosed a process for the preparation of an alpha-aminoketone salt of formula I ##STR1## which comprises reacting a nitrosated keto ester of formula II ##STR2## with a carboxylic anhydride of formula IV ##STR3## under the conditions of catalytic hydrogenation, to a compound of formula III ##STR4## which compound of formula III is then hydrolysed with an acid H.sub.n A to the salt I, in which formulae above R.sub.1 is C.sub.1 -C.sub.6 alkyl, phenoxy-C.sub.1 -C.sub.4 alkyl, phenyl, C.sub.7 -C.sub.9 phenylalkyl, or phenyl or C.sub.7 -C.sub.9 phenylalkyl which are substituted by halogen, C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkoxy, hydroxy or cyano, R.sub.2 is C.sub.1 -C.sub.4 alkyl or cyclohexyl, n is 1 to 3, R.sub.3 is C.sub.1 -C.sub.4 alkyl and A is the radical of an organic or mineral protic acid.Pyrroles suitable as co-stabilisers for PVC can be prepared from alpha-aminoketone salts of formula I.Type: GrantFiled: September 8, 1993Date of Patent: June 21, 1994Assignee: Ciba-Geigy CorporationInventors: Rolf Drewes, Hans-Helmut Friedrich
-
Patent number: 5321139Abstract: Two processes are described for the preparation of the optically pure compounds of formula 1: ##STR1## in which R.sup.1 and R.sup.2 are e.g. alkyl, R.sup.3 and R.sup.4 are e.g. hydrogen and R.sup.5 is e.g. hydrogen. Both processes include, as key steps, the enantioselective hydrogenation of a C.dbd.C double bond and the regioselective formation of a dicarboxylic acid monoamide derivative. In one process a phenylitaconic acid derivative is asymmetrically hydrogenated to give an optically active (R)-benzylsuccinic acid which is then converted to a diester, said diester being converted to the monoamide compound of formula 1. In the second process, a phenylitaconic acid derivative is converted to its anhydride, and the anhydride is then converted to a monoamide which is then asymmetrically hydrogenated to give the compound of formula 1.Type: GrantFiled: February 16, 1993Date of Patent: June 14, 1994Assignee: Hoechst AktiengesellschaftInventors: Ulrich Lerch, Heiner Jendralla, Bernhard Seuring, Rainer Henning
-
Patent number: 5321150Abstract: 5-Deaza-10-oxo- and 5-deaza-10-thio-5,6,7,8-tetrahydrofolic acid derivatives are provided as agents useful for treating susceptible neoplasms in mammals. Pharmaceutical formulations and intermediates are also provided.Type: GrantFiled: July 7, 1992Date of Patent: June 14, 1994Assignee: Eli Lilly and CompanyInventors: Homer L. Pearce, Mark A. Winter
-
Patent number: 5304671Abstract: A method for the recovery of .alpha.-L-aspartyl-L-phenylalanine methyl ester, L-phenylalanine and L-aspartic acid from the mother liquor obtained by the solid-liquid separation of a suspension of .alpha.-L-aspartyl-L-phenylalanine methyl ester crystals is disclosed.Type: GrantFiled: August 5, 1992Date of Patent: April 19, 1994Assignee: Ajinomoto Co., Inc.Inventors: Sou Abe, Shinichi Kishimoto, Tadashi Takemoto, Toshihisa Kato, Satoshi Kumon
-
Patent number: 5302743Abstract: Disclosed is an improved process for the preparation of an N-protected .alpha.-L-aspartyl-L-phenylalanine methyl ester from an N-protected L-aspartic anhydride and L-phenylalanine methyl ester, the improvement which comprises employing the L-phenylalanine methyl ester in the form of a mineral acid salt thereof and conducting the reaction either (a) in an organic solvent and in the presence of a salt of an organic carboxylic acid, or (b) in an organic solvent comprising an organic carboxylic acid and in the presence of at least one member of the group consisting of an alkali metal or an alkaline earth metal inorganic base, an ammonium alkali metal or alkaline earth metal salt of an organic carboxylic acid and ammonium carbonate. The starting N-protected aspartic anhydride, e.g., N-benzyloxycarbonyl-L-aspartic anhydride, can be produced by the reaction of N-protected aspartic acid with phosgene.Type: GrantFiled: January 21, 1992Date of Patent: April 12, 1994Assignee: Mitsui Toatsu Chemicals, Inc.Inventors: Toshio Katoh, Chojiro Higuchi, Takeshi Oura, Masanobu Ajioka, Akihiro Yamaguchi
-
Patent number: 5298647Abstract: Aromatic compounds absorbing UVB and/or UVA, substituted with an amide function, selected from the group consisting of ##STR1## whose variable substituents are as defined in the specification, e.g. ##STR2## are useful as photoprotective agents or tanning accelerators.Type: GrantFiled: December 14, 1987Date of Patent: March 29, 1994Inventors: Dominique Robert, Louis Jung
-
Patent number: 5298652Abstract: Compounds of the formula ##STR1## R is hydrogen or --CH.sub.2 COOH; m is 0-2,x is 1-2, with the provision that when x is 2, m is always 0;R.sub.1 is CH.sub.3 (CH.sub.2).sub.n O--, CH.sub.3 (CH.sub.2).sub.n CONH--, CH.sub.3 (CH.sub.2).sub.n NHCONH--, CH.sub.3 (CH.sub.2).sub.n NHCOO--, HOOC(CH.sub.2).sub.p O-- or R.sub.3 (CH.sub.2).sub.q O--;R.sub.2 is hydrogen, carboxy, hydroxy, nitro, amino, CH.sub.3 (CH.sub.2).sub.n O--, CH.sub.3 (CH.sub.2).sub.n CONH--, CH.sub.3 (CH.sub.2).sub.n NHCONH--, CH.sub.3 (CH.sub.2).sub.n NHCOO--, HOOC(CH.sub.2).sub.p O--, R.sub.3 (CH.sub.2).sub.q O-- or R.sub.4 [O(CH.sub.2).sub.2 ].sub.r O--,wherein n is 0-17, p is 1-10, q is 1-12, r is 1-6,R.sub.3 is 1- or 2- naphthyloxy, 2,3- or 3,4-dihydroxyphenyl, phenyl, phenoxy or substituted phenyl or phenoxy, wherein the substituent is selected from the group consisting of lower alkyl, lower alkoxy, hydroxy, nitro, amino, halo, carboxy or phenyl, andR.sub.4 is lower alkyl;and pharmaceutically acceptable salts with bases,are described.Type: GrantFiled: December 8, 1992Date of Patent: March 29, 1994Assignee: Hoffmann-La Roche Inc.Inventors: Mathew Carson, Ru-Jen L. Han, Ronald A. LeMahieu, Vincent S. Madison
-
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
-
Patent number: 5296591Abstract: The trifluoromethylketone derivatives (I) and pharmaceutically acceptable salts thereof have a human leukocyte elastase inhibiting activity and are useful as human leukocyte elastase inhibitors for treating or preventing degenerative diseases. The trifluoromethylketone derivatives (I) have the following formula: ##STR1## wherein R.sup.1 is C.sub.1-6 alkyl which has one or two substituents selected from carboxy, esterified carboxy and di-C.sub.1-6 alkylcarbamoyl; phenyl(C.sub.1-6) alkyl, the phenyl moiety of which may have halogen or nitro or amino substituents and the alkyl moiety of which may have carboxy or esterified carboxy substituents; halo-phenyl; morpholino; or morpholino(C.sub.1-6) alkyl,R.sup.2 and R.sup.3 are each C.sub.1-6 alkyl,X is -- or --NH--, andY is ##STR2## and pharmaceutically acceptable salts thereof.Type: GrantFiled: December 12, 1991Date of Patent: March 22, 1994Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Keiji Hemmi, Ichiro Shima, Keisuke Imai, Hirokazu Tanaka
-
Patent number: 5294616Abstract: A series of non-peptide derivatives that are antagonists of the fibrinogen IIb/IIIa receptor and thus are platelet aggregation compounds useful in the prevention and treatment of diseases caused by thrombus formation.Type: GrantFiled: March 25, 1992Date of Patent: March 15, 1994Assignee: Merck & Co., Inc.Inventors: Mark E. Duggan, Melissa S. Egbertson, Wasyl Halczenko, George D. Hartman, Laura M. Turchi, William L. Laswell
-
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
-
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
-
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
-
Patent number: 5283357Abstract: A method for separating .alpha.-L-aspartyl-L-phenylalanine methyl ester (.alpha.-APM) from a solution containing .alpha.-APM and impurities associated with the production thereof which comprises adding a mineral acid or an organic sulfonic acid to the solution in an organic carboxylic acid or in a solvent containing an organic carboxylic acid, and isolating the pure salt of .alpha.-APM which precipitates therefrom.Type: GrantFiled: April 23, 1991Date of Patent: February 1, 1994Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Toshio Katoh, Chojiro Higuchi, Takeshi Oura, Masanobu Ajioka, Akihiro Yamaguchi
-
Patent number: 5275702Abstract: The present invention discloses a method to separate each component from a mixed solution of organic solvents obtained during the production of .alpha.-L-aspartyl-L-phenylalanine methyl ester, which is useful as a sweetener, namely, a mixed solution of acetic acid and toluene or a mixed solution of acetic acid, toluene and formic acid, recovering each component with a high recovery ratio with as small number of operations as possible. The method rationalizes the process and is highly valuable in practical use.Type: GrantFiled: August 12, 1992Date of Patent: January 4, 1994Assignee: Ajinomoto Co., Inc.Inventors: Takehiko Kataoka, Haruo Kawasaki, Harutoshi Ohura, Yoshinobu Uchida, Akihiko Yasaki, Shinichi Kishimoto
-
Patent number: 5274188Abstract: The invention relates to a novel process for the manufacture of (3R,1'R)-4-acyloxy-3-(1'-hydroxyethyl)-2-azetidinones of formula ##STR1## in which R.sup.1 represents lower alkyl or aryl, by enantioselective reduction of the carbonyl group in a suitable .alpha.-acylaminomethyl-acetoacetic acid ester, cyclisation of the resulting .alpha.-acylaminomethyl-.beta.-hydroxybutyric acid ester to a 5,6-dihydro-1,3,4H-oxazine with inversion of the carbon atom carrying the hydroxy group, equilibration to form the preferred trans-substituted dihydrooxazine, recleaving to form the configuratively uniform .alpha.-aminomethyl-.beta.-hydroxybutyric acid, ring-closure to form the .beta.-lactam and oxidative acylation at C(4) of the .beta.-lactam. Compounds of formula I can be used as starting materials for the manufacture of .beta.-lactam antibiotics. The invention relates also to novel intermediates.Type: GrantFiled: August 6, 1991Date of Patent: December 28, 1993Assignee: Ciba-Geigy CorporationInventors: Peter Schneider, Gerardo Ramos
-
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
-
Patent number: 5266591Abstract: The compounds are ethanolamine benzoate compounds useful for the treatment of syndrome X, and of hypertension in patients who are insulin resistant or have one or more metabolic anomalies.A compound disclosed is S-1-(m-trifluoromethylphenyl)-2-{.beta.-{4-[2-(N-(3,3-diphenylpropionyl)am ino)ethyl] benzoyloxy}ethylamino} propane.Type: GrantFiled: November 20, 1992Date of Patent: November 30, 1993Assignee: Adir et CompagnieInventors: Michel Wierzbicki, Pierre Hugon, Jacques Duhault, Michelle Boulanger, Francoise Lacour
-
Patent number: 5252745Abstract: Antimicrobial compounds of the formula ##STR1## wherein R.sup.1 is selected from the group consisting of H, an amine protective group, and a moiety of the formula ##STR2## wherein R.sup.2, R.sup.5, and R.sup.6 are independently selected from H and an amine protective group;R.sup.3 and R.sup.4 are independently selected from H, lower alkyl, aryl, arylalkyl, CH.sub.2 OR, CH.sub.2 SR or CH(CH.sub.3)OR;R=H, propargyl lower alkyl, arylalkyl or aryl;wherein R.sup.1 and R.sup.2 or R.sup.5 and R.sup.6 can be joined to form a ring; and wherein when R.sup.1 and R.sup.2 or R.sup.5 and R.sup.6 are both H, the compound is either in free base form or in salt form.Type: GrantFiled: May 21, 1991Date of Patent: October 12, 1993Assignee: Rohm and Haas CompanyInventors: Margaret M. Bowers-Daines, Barry C. Lange
-
Patent number: 5248806Abstract: An acid addition salt of .alpha.-APM is dissolved or suspended in an aqueous medium at 50.degree. C. or lower at a pH of 3 or less and a concentration of the salt of 3 wt.% or more (solution A). A liquid having a pH of 3 or more and containing or not containing .alpha.-APM is prepared (solution B) and gradually mixed with solution A with stirring. The temperature of the liquid mixture is kept to be 40.degree. C. or lower and the pH value of the mixture is kept at 3 or more, optionally adding a base thereto, whereby crystals of .alpha.-APM are precipitated out.Type: GrantFiled: May 20, 1992Date of Patent: September 28, 1993Assignee: Ajinomoto Co., Inc.Inventors: Shinichi Kishimoto, So Abe, Toshihisa Kato
-
Patent number: 5241099Abstract: Aminomethylene compounds of the formula ##STR1## can be prepared by reaction of C-H-acid compounds of the formula ##STR2## with salts of the formula ##STR3## in the presence of simple inorganic bases, where the radicals R.sup.1 to R.sup.4, R.sup.7, R.sup.8 and X.sup..crclbar. have the meanings given in the description.Type: GrantFiled: March 16, 1992Date of Patent: August 31, 1993Assignee: Bayer AktiengesellschaftInventors: Heinz-Ulrich Blank, Helmut Kraus
-
Patent number: 5231113Abstract: Retinoid-like activity is exhibited by compounds of the formula ##STR1## where the R groups are independently hydrogen, or lower alkyl; A is --C(O)O--, --OC(O)--, --C(O)S--, or --SC(O)--; n is 0-5; and Z is H, --COB where B is --OH or a pharmaceutically acceptable salt, or B is --OR.sub.1 where R.sub.1 is an ester-forming group, or B is --N(R).sub.2 where R is hydrogen or lower alkyl, or Z is --OE where E is hydrogen or an ether-forming group or --COR.sub.2 where R.sub.2 is hydrogen, lower alkyl, phenyl or lower alkyl phenyl, or Z is --CHO or an acetal derivative thereof, or Z is --COR.sub.3 where R.sub.3 is --(CH.sub.2).sub.m CH.sub.3 where m is 0-4 and the sum of n and m does not exceed 4.Type: GrantFiled: June 4, 1992Date of Patent: July 27, 1993Assignee: Allergan, Inc.Inventors: Roshantha A. S. Chandraratna, Robert J. Weinkam
-
Patent number: 5225587Abstract: A method of purifying .alpha.-L-aspartyl-L-phenylalanine methyl ester as a hydrochloride salt thereof which comprises:i) contacting a mixture of .alpha.-L-aspartyl-L-phenylanaline methyl ester and .beta.-L-aspartyl-L-phenylalanine methyl ester with an aqueous medium containing (a) hydrogen chloride in an amount not more than ca. 2 mol., per liter of said aqueous medium, but not less than 1 mol., per mole of said of said mixture of .alpha.-L-aspartyl-L-phenylalanine methyl ester and .beta.-L-aspartyl-L-phenylalanine methyl ester, and (b) an inorganic chloride selected from the group consisting of NaCl, KCl, NH.sub.4 Cl, CaCl.sub.2, and ZnCl.sub.2 in an amount of at least ca. 50 g., per liter of said aqueous medium, to form crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride, andii) recovering the .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride crystals therefrom.Type: GrantFiled: April 6, 1992Date of Patent: July 6, 1993Assignee: Ajinomoto Co., Inc.Inventors: Katsumi Sugiyama, Kiyo Adachi, Toshihide Yukawa
-
Patent number: 5217996Abstract: The invention relates to biaryl substituted 4-amino-butyric acid derivatives of formula I ##STR1## wherein COX and COX' independently represent carboxyl or carboxyl derivatized in form of a pharmaceutically acceptable ester or amide; R.sub.1 represents hydrogen, lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl, aryl-lower alkyl, biaryl-lower alkyl, lower alkoxy, aryl-lower alkoxy, aryloxy, N-lower alkylamino, N,N-di-lower alkylamino, N-aryl-lower alkylamino, N,N-di-aryl-lower alkylamino, N-arylamino, N,N-diarylamino, lower alkanoylamino, aryl-lower alkanoylamino or aroylamino; R.sub.2 represents hydrogen, hydroxy, lower alkoxy, lower alkyl, aryl-lower alkyl, C.sub.3 -C.sub.Type: GrantFiled: January 22, 1992Date of Patent: June 8, 1993Assignee: Ciba-Geigy CorporationInventor: Gary Ksander
-
Patent number: 5214056Abstract: A 1,3,2-dioxathiolane oxide derivative is represented by the following formula: ##STR1## wherein X represents --S(O)-- or --S(O).sub.2 --;R.sup.1 represents a hydrogen atom, an alkali metal atom, a benzyl group, or a lower alkyl group;R.sup.2 represents a lower alkyl group which may be substituted with a methylthio group, or a benzyl group, andR.sup.3 and R.sup.4 may be the same or different and independently represent a hydrogen atom, an alkyl group having one to ten carbon atoms, a lower alkyl group substituted with a guanidyl group, a cycloalkyl group having 3 to 6 carbon atoms, a phenyl group, a benzyl group, or a phenethyl group, or together form an alkylene group.Type: GrantFiled: August 20, 1991Date of Patent: May 25, 1993Assignee: Japan Tobacco Inc.Inventors: Jun-ichi Haruta, Masahiro Tanaka, Itsuo Uchida, Akira Ohta, Shin Hara
-
Patent number: 5206413Abstract: A method for preparing .alpha.-L-aspartyl-L-phenylalanine methyl ester (.alpha.-APM), substantially free from acid ion contamination, is disclosed which comprises the steps of contacting a solution of a mineral acid salt or an organic sulfonic acid salt of .alpha.-APM in an aqueous solvent with an anion exchange resin in free base form, separating the resin from the thus-produced solution of .alpha.-APM; and isolating the .alpha.-APM therefrom, preferably with regeneration and recycling the resin.Type: GrantFiled: June 14, 1990Date of Patent: April 27, 1993Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Masanobu Ajioka, Takeshi Oura, Chojiro Higuchi, Toshio Katoh, Akihiro Yamaguchi
-
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
-
Patent number: 5196576Abstract: A chelating compound of the formula:(R-NHOC-CH.sub.2).sub.n --A--(CH.sub.2 COOH).sub.m (I)wherein R is an aromatic ring-containing organic group, A is a residue of an aminopolyacetic acid excluding acetic acid groups (--CH.sub.2 COOH) therefrom, m is an integer of at least two and n is an integer of 1 or 2, or its salt, which has a specificity to a hepatobiliary system so that a complex formed between said chelating compound and a metallic element through a covalent bond is useful as a diagnostic or therapeutic agent for hepatobiliary organs and tissues.Type: GrantFiled: April 9, 1991Date of Patent: March 23, 1993Assignee: Nihon Medi-Physics Co., Ltd.Inventors: Shigemi Seri, Hirohiko Yamauchi, Makoto Azuma, Yoji Arata
-
Patent number: 5192358Abstract: Oxalylhydroxamic acid derivatives of the formula IR.sup.1 --ON(R.sup.2)--CO--CO--X--R.sup.3 I,where the substituents have the following meanings:X is oxygen or sulfur;R.sup.1 issubstituted or unsubstituted alkyl, alkenyl or alkynyl;substituted or unsubstituted monocyclic or polycyclic cycloalkyl or cycloalkylmethyl;substituted or unsubstituted phenyl or phenyl-C.sub.1 -C.sub.4 -alkyl;R.sup.2 is hydrogen or alkyl;R.sup.3 issubstituted or unsubstituted alkyl, alkenyl or alkynyl;substituted or unsubstituted monocyclic or polycyclic cycloalkyl;substituted or unsubstituted phenyl-C.sub.1 -C.sub.4 -alkyl or phenoxy-C.sub.1 -C.sub.4 -alkyl;and their agriculturally useful salts; their manufacture; growth-regulating agents containing them; and methods of regulating plant growth.Type: GrantFiled: July 1, 1991Date of Patent: March 9, 1993Assignee: BASF AktiengesellschaftInventors: Costin Rentzea, Wilhelm Rademacher
-
Patent number: 5180744Abstract: Non-peptidyl compounds characterized generally as aralkyl-N-terminal amino hydroxy .beta.-amino acid derivatives are useful as renin inhibitors for treatment of hypertension. Compounds of particular interest are of the formula ##STR1## wherein R.sub.1 is selected from ##STR2## wherein each of Y and Z is independently selected from hydrido, chloro, fluoro, methoxy and dimethylamino; wherein n is a number selected from zero through four, inclusive; wherein each of R.sub.2 and R.sub.4 is independently selected from hydrido and methyl; wherein R.sub.3 is methyl or ethyl; wherein R.sub.5 is cyclohexylmethyl; wherein R.sub.6 is hydroxy; wherein R.sub.7 is isobutyl or ethyl; and wherein each of R.sub.8 and R.sub.9 is hydrido; or a pharmaceutically-acceptable salt thereof.Type: GrantFiled: July 29, 1991Date of Patent: January 19, 1993Assignee: G. D. Searle & Co.Inventors: Gunnar J. Hanson, John S. Baran, Dave Weissing, Mark Russell
-
Patent number: 5177109Abstract: Compounds, compositions and methods are described for treating a CNS disorder such as a cognitive disorder, epilepsy, depression, Parkinson's disease, Alzheimer's disease, a neurodegenerative disease or neurotoxic injury. Compound of interest are 2-amino-4,5-methyleneadipic acid compounds and derivatives defined by the formula I: ##STR1## wherein R.sup.1 is selected from hydrido, alkyl, cycloalkyl, aralkyl, aryloxyalkyl, arylthioalkyl, ##STR2## with each of R.sup.2, R.sup.3, R.sup.4 and R.sup.5 being independently selected from hydrido, alkyl, cycloalkyl, aryl and aralkyl; wherein each of X and Y is independently selected from hydroxyl, alkoxy, alkylthio, amino and ##STR3## with each of R.sup.6 and R.sup.7 being independently selected from hydrido, alkyl, cycloalkyl, aryl and aralkyl; wherein any of R.sup.1 through R.sup.Type: GrantFiled: July 19, 1991Date of Patent: January 5, 1993Assignee: G. D. Searle & Co.Inventors: Roberto Pellicciari, Benedetto Natalini, Maura Marinozzi, Alexis A. Cordi, Joseph B. Monahan, Thomas H. Lanthorn
-
Patent number: 5169976Abstract: Variously substituted 4-(biphen-2-ylmethylcarbamoyl)-3-hydroxybutyric acids and esters, also named as N-(biphen-2-yl)-3-hydroxyglutaramic acid derivatives, are blood cholesterol lowering agents and so are useful in the prevention and treatment of cardiovascular diseases such as atherosclerosis.Type: GrantFiled: May 3, 1990Date of Patent: December 8, 1992Assignee: Pfizer Inc.Inventor: Peter A. McCarthy
-
Patent number: 5162311Abstract: The invention discloses certain substituted .alpha.-aminoacids having the formula ##STR1## where m and n are 1 or 2, and R, R.sub.1, R.sub.2, R.sub.3 and Y have various significances, which compounds are useful in treating epilepsy, disorders associated with excess GH or LH secretion, anxiety, schizophrenia, depression, CNS degenerative disorders, cerebral hypoxic conditions and stress-related psychiatric disorders.Type: GrantFiled: August 19, 1991Date of Patent: November 10, 1992Assignee: Sandoz Pharmaceuticals Corp.Inventors: Paul L. Herrling, Werner Muller
-
Patent number: 5157145Abstract: Process for producing dipeptides from non-proteinogenic amino acids with terminal carbon atoms.Type: GrantFiled: July 17, 1990Date of Patent: October 20, 1992Assignee: BASF AktiengesellschaftInventors: Ulrich Schoellkopf, Ulrich Groth, Meinolf Lange
-
Patent number: 5155100Abstract: The invention relates to the N-phosphonomethyl-biaryl substituted dipeptide derivatives of formula I ##STR1## wherein A represents a direct bond, lower alkylene, phenylene or cyclohexylene; m represents 1 or zero, provided that m represents 1 when A is a direct bond; R.sub.2 represents hydrogen, hydroxy, lower alkyl, aryl-lower alkyl, C.sub.5 -C.sub.Type: GrantFiled: May 1, 1991Date of Patent: October 13, 1992Assignee: Ciba-Geigy CorporationInventors: Mark D. Erion, Stephane De Lombaert
-
Patent number: 5145874Abstract: Provided are cyclic hydrocarbons of Formula I ##STR1## with an aminoalkyl sidechain that are useful for treating phospholipase A2 mediated conditions, diabetes, and obesity.Type: GrantFiled: February 25, 1991Date of Patent: September 8, 1992Assignee: The Upjohn CompanyInventors: Roy A. Johnson, Gordon L. Bundy, Gilbert A. Youngdale, Douglas R. Morton, Donald P. Wallach, deceased, by Vera M. Wallach, legal representative
-
Patent number: 5138071Abstract: A process for preparing dipeptides with N-terminal non-proteinogenous amino acids of the formula ##STR1## in which R.sup.1 to R.sup.6 have the meaning stated in the description, from compounds of the formula ##STR2## is described.Type: GrantFiled: March 18, 1991Date of Patent: August 11, 1992Assignee: BASF AktiengesellschaftInventors: Ulrich Schoellkopf, Ulrich Groth, Meinolf Lange
-
Patent number: RE34652Abstract: Novel fluorinated, acrylamide monomers are prepared from 2-alkenyl azlactones reacted with fluorinated alcohols. The novel monomers have the formula ##STR1## wherein R.sup.1 and R.sup.6 are independently hydrogen or methyl;R.sup.2 and R.sup.3 independently can be an alkyl, cycloalkyl, or aryl group, or R.sup.2 and R.sup.3 taken together with the carbon to which they are joined can form a carbocyclic ring containing 4 to 12 ring atoms;R.sup.4 and R.sup.5 are independently hydrogen or lower alkyl;a is 0 or 1;b is 1 or 2;X is a single bond, CH.sub.2, CH.sub.2 OCH.sub.2, and CH.sub.2 CH.sub.2 OCH.sub.2 ; andR.sub.F is a substantially perfluorinated alkyl, cycloalkyl, or aryl group when b is 1 and perfluorinated alkylene when b is 2.Novel polymers and copolymers can be prepared from the monomers of the invention.Type: GrantFiled: June 3, 1992Date of Patent: June 28, 1994Assignee: Minnesota Mining and Manufacturing CompanyInventors: Steven M. Heilmann, Larry R. Krepski, Dean M. Moren, Jerald K. Rasmussen, Howell K. Smith, II