Nitrogen Bonded Directly To The Pteridine Ring System Patents (Class 544/258)
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Patent number: 5446156Abstract: A process for the preparation of salts of (6R)-N(5),N(10)-methenyl-5,6,7,8-tetrahydrofolic acid of a particular formula (I). The process comprises:(i) mixing at least one acid S.sub.1 with an aqueous solution having dissolved therein an ammonium- or alkali metal-salt of (6RS)-N(10)-formyl-5,6,7,8-tetrahydrofolic acid of a particular formula (II) until a pH in the range of about 5.5 to 7.5 is obtained;(ii) adding a water-soluble alkaline earth metal salt to the mixture obtained from step (i);(iii) precipitating a solid and isolating the solid;(iv) providing a solid of formula (I) by suspending the solid obtained from step (iii) in water, adding an acid S.sub.2, which will not precipitate with an alkaline earth metal cation, until the pH stabilizes to a value of 1.0 to 2.0, and separating the resulting solid.Type: GrantFiled: December 21, 1992Date of Patent: August 29, 1995Assignee: Sapec S.A. fine chemicalsInventors: Pascal Jequier, Fabrizio Marazza
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Patent number: 5391738Abstract: The treatment of racemic calcium folinate with a sodium salt of ethylendiaminotetraacetic acid and, preferably, calcium cloride determines the separation of a precipitate, whose mother liquors result enriched in a calcium salt of the levofolinic acid, purifiable through repeated crystallizations.Type: GrantFiled: August 16, 1993Date of Patent: February 21, 1995Assignee: APR Applied Pharma Research S.A.Inventor: Guiseppe Vecchi
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(6R)- and (6S)-diastereoisomers of an ammonium salts of N.sup.5 -methyl-5,6,7,8-tetrahydrofolic acid
Patent number: 5382581Abstract: There are described ammonium salts of N.sup.5 -methyl-5,6,7,8-tetrahydrofolic acid as well as processes for their preparation. These ammonium salts may be separated into the single (6R) and (6S)-diastereoisomers. The separated diastereoisomers may be transformed into the corresponding alkali metal or alkaline earth metal salts.Type: GrantFiled: November 13, 1992Date of Patent: January 17, 1995Assignee: Sapec S.A. fine chemicalsInventors: Fabrizio Marazza, Jean Jacques -
Patent number: 5350850Abstract: Process for the preparation of the optically active [6(S)(-)]N.sup.5 alkaline earth metal salts of methyltetrahydrofolic acid and formyltetrahydrofolic acid wherein an aqueous solution of folic acid is hydrogenated with a high stoichiometric excess of sodium borohydride followed by treating the reaction product with formic aldehyde and optionally further with sodium borohydride when the methyl derivative is desired. Reaction with a salt of the alkaline earth metal precipitates the desired optically active alkaline earth metal salt.Type: GrantFiled: October 7, 1992Date of Patent: September 27, 1994Assignee: APR Applied Pharma Research S.A.Inventor: Giuseppe Vecchi
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Patent number: 5350851Abstract: Intermediates and a process for the synthesis of 6-monosubstituted tetrahydropteridine C6-stereoisomers, including (6S)-tetrahydrofolic acid. The intermediates are shown in their two enantiomeric forms as follows: ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and represent hydrogen, methyl, hydroxy, amino, alkyl or dialkylamino, alkoxy, benzyloxy, or benzylthio; R.sub.3 represents an alkene, alkyne, cycloalkyl, benzyl, alkyl (substituted with hydroxy, acetoxy, benzyloxy, alkoxy, alkylthio, amino, carboxy, oxo, or phosphate), a protected aldehyde, or ##STR2## wherein n=1 or 2, R.sub.4 is hydrogen, formyl, methyl, or propargyl, and ZZ represents an amino acid or amino acid polymer.Type: GrantFiled: November 25, 1992Date of Patent: September 27, 1994Assignee: South Alabama Medical Science FoundationInventors: Steven W. Bailey, June E. Ayling
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Patent number: 5350749Abstract: 4-substituted-pyrido[3,2-d]pyridmidine, -pyrido[4,3-d]pyrimidine, -pyrido[3,4-d]pyrimidine, pyrido[2,3-d]pyrimidine, -pteridine, -pyrimido[4,5-d]pyrimidine, -pyrimido[4,5-c]pyridazine, -pyrimido[5,4-d]pyrimidine, -pyrimido[5,4-c]pyridazine, pyrimido[4,5-d]pyridazine, and pyrimido[5,4-e]-1,2,4-triazine derivatives, for example 4-[2-(4-chlorophenyl)ethoxy]pyrido[2,3-d]pyrimidine, are useful as fungicides, inseciticides and miticides.Type: GrantFiled: April 22, 1991Date of Patent: September 27, 1994Assignee: DowElancoInventors: Ronald E. Hackler, Glen P. Jourdan
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Patent number: 5347005Abstract: The invention relates to a process for preparing (6S)-folinic acid and its salts by recrystallization of alkaline-earth salts of (6R,S)-folinic acid and, where necessary, liberation of the acid from the alkaline-earth folinates and/or, where necessary, conversion into the alkali salts by at least one recrystallization in the presence of a base.The invention also relates to calcium-, magnesium-, potassium- and sodium-(6S)-folinates and to (6S)-folinic acid prepared in accordance with the invention.Type: GrantFiled: June 2, 1992Date of Patent: September 13, 1994Assignee: Eprova AGInventors: Hans R. Mueller, Martin Ulmann, Josef Conti, Gunter Muerdel
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Patent number: 5332815Abstract: A process for the preparation of alkaline earth metal salts of (6R)-N(10)-formyl-5,6,7,8-tetrahydrofolic acid. An alkaline earth metal salt, either in the form of a solid, or in the form of an aqueous solution, is added, preferably under an inert gas atmosphere, to an ammonium salt or alkali metal salt of (6RS)-N(10)-formyl-5,6,7,8-tetrahydrofolic acid dissolved in water or an aqueous buffer solution. II is added an alkaline earth metal salt either in the form of a solid or in the form of an aqueous solution. The obtained mixture is allowed to crystallize, and the obtained solid is separated. The product is known to be cytostatic.Type: GrantFiled: October 2, 1992Date of Patent: July 26, 1994Assignee: Sapec S.A. fine chemicalsInventors: Attilio Melera, Fabrizio Marazza
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Patent number: 5326766Abstract: Compounds of the formula (I): ##STR1## wherein: Het is pyridyl, pyrazinyl, pyrimidinyl, or pyridizinyl, optionally substituted with one or more groups selected from halo, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy, NO.sub.2, CN, and lower alkoxy-carbonyl;Z is a C--C single bond, CH.sub.2, NH, O, S, --CH.sub.2 O--, or --OCH.sub.2 --; andthe remaining groups are as defined in the specification are useful as pesticides.Type: GrantFiled: August 19, 1992Date of Patent: July 5, 1994Inventors: Barry A. Dreikorn, Sylvester V. Kaster, Neil V. Kirby, Robert G. Suhr, Brian R. Thoreen
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Patent number: 5324836Abstract: For the preparation of (6S)- and (6R)-tetrahydrofolic acid and their addition salts with a sulfonic acid or with sulfuric acid, (6R,S)-tetrahydrofolic acid is reacted with a sulfonic acid or with sulfuric acid, the resulting acid addition salt is fractionally crystallized and, if desired, the (6S)- or (6R)-tetrahydrofolic acid is liberated from the resulting diastereomeric acid addition salts by treatment with a base and isolated.Type: GrantFiled: April 8, 1993Date of Patent: June 28, 1994Assignee: Eprova AkteingesellschaftInventors: Hans R. Muller, Martin Ulmann, Josef Conti, Gunter Murdel
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Patent number: 5286726Abstract: This invention relates to certain conjugates of folates and antifolates with difluoroglutamic acid which are useful in the treatment of patients suffering from certain neoplastic diseases including leukemia, melanomas, carcinomas, sarcomas and mixed neoplasias.Type: GrantFiled: April 12, 1990Date of Patent: February 15, 1994Assignees: The Regents of the University of Michigan, Health Research, Inc., Merrell Dow Pharmaceuticals Inc.Inventors: Philippe Bey, James K. Coward, John J. McGuire
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Patent number: 5283247Abstract: Disclosed herein are substituted quinazolones and their N.sup.1 -oxide derivatives, methods of synthesizing such compounds, and methods of using them to treat or prevent convulsions in mammals. The substituted quinazolones are represented by the formula: ##STR1## wherein X.sub.1 is N, S, O, or CH, X.sub.2 is N or CH, R.sub.1 and R.sub.2 are H, NO.sub.2, or NH.sub.2 except that when one of R.sub.1 and R.sub.2 is NO.sub.2 or NH.sub.2 the other is H, R.sub.3 and R.sub.4 are alkyl with 1-5 C atoms, and R.sub.5, R.sub.6, and R.sub.7 are H or halogen, provided that when X.sub.1 is N, S, or O, X.sub.2 is CH.Type: GrantFiled: September 21, 1992Date of Patent: February 1, 1994Assignee: Research Corporation Technologies, Inc.Inventors: Chandradhar Dwivedi, Gary W. Omodt
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Patent number: 5270465Abstract: The present invention relates to 4(3H)-pteridinones represented by the formula: ##STR1## in which X is an oxygen atom or a sulphur atom, Y is a hydrogen atom, a lower alkyl radical, especially a methyl radical, at the 6-position or a hydroxyl group at the 7-position, R.sub.1 is a hydrogen atom, a lower alkyl radical, a substituted or unsubstituted phenyl radical, a benzyl radical, a methoxymethyl group, an acetyl group, a 2-acetoxyethyl group or a 2,2,2-trifluoroethyl group and R.sub.2 is a hydrogen atom or a lower alkyl radical, especially a methyl radical.Application of these compounds as anti-allergic drugs.Type: GrantFiled: November 3, 1992Date of Patent: December 14, 1993Assignee: Lipha, Lyonnaise Industrille PharmaceutiqueInventors: Gerard Ferrand, Herve Dumas, Jean-Claude Depin, Yvette Quentin
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Patent number: 5254686Abstract: A procaine acid addition salt, wherein the acid is attached to the diethylamino nitrogen, is complexed with a biologically active organic acid such as a vitamin acid, essential unsaturated fatty acid, C.sub.4 to C.sub.6 hydroxycarboxylic acid or alpha amino acid in stoichiometric ratios of organic acid to procaine acid addition salt to form a double salt complex wherein the organic acid attaches to the p-amino nitrogen. Such double salt complexes protect the procaine molecule from cholinesterase hydrolysis when orally administered to warm blooded animals allowing the complex to be carried intact to the site of damaged cells and across the cell membrane where the double salt complex is disassociated in the cell releasing the organic acid and procaine for cellular repair and regeneration. Procaine hydrochloride is the preferred procaine salt. Preferred acids are citric and vitamin acids including nicotinic acid, ascorbic acid, biotin and folic acid.Type: GrantFiled: September 25, 1992Date of Patent: October 19, 1993Inventor: Robert Koch
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Patent number: 5241070Abstract: This invention is directed to novel nucleophilic polysubstituted aryl acridinium esters and to novel conjugates thereof. The novel nucleophilic polysubstituted aryl acridinium esters and novel conjugates thereof are useful in biological assays, including novel assays for the determination of Vitamin B.sub.12, folate, cortisol, estradiol, and thromboxane B.sub.2.Type: GrantFiled: April 17, 1992Date of Patent: August 31, 1993Assignee: Ciba Corning Diagnostics Corp.Inventor: Say-Jong Law
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Patent number: 5198547Abstract: Intermediates and a process for the synthesis of 6-monosubstituted tetrahydropteridine C6-stereoisomers, including (6S)-tetrahydrofolic acid. The intermediates are shown in their two enantiomeric forms as follows: ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and represent hydrogen, methyl, hydroxy, amino, alkyl or dialkylamino, alkoxy, benzyloxy, or benzylthio; R.sub.3 represents an alkene, alkyne, cycloalkyl, benzyl, alkyl (substituted with hydroxy, acetoxy, benzyloxy, alkoxy, alkylthio, amino, carboxy, oxo, or phosphate), a protected aldehyde, or ##STR2## wherein n=1 or 2, R.sub.4 is hydrogen, formyl, methyl, or propargyl, and ZZ represents an amino acid or amino acid polymer. Also, a process for tetrahydropteridine N5-formylation for the preparation of, for example, N5-formyl-(6S)-tetrahydrofolic acid.Type: GrantFiled: March 16, 1992Date of Patent: March 30, 1993Assignee: South Alabama Medical Science Foundation, USAInventors: Steven W. Bailey, June E. Ayling
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Patent number: 5196533Abstract: 6,6-Disubstituted pteridines which are useful for the regulation of enzymes are disclosed, along with a general method of synthesizing these compounds.Type: GrantFiled: March 14, 1991Date of Patent: March 23, 1993Assignee: South Alabama Medical Science Foundation, USAInventors: June E. Ayling, Steven W. Bailey
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Patent number: 5194611Abstract: There are described ammonium salts of N.sup.5 -methyl-5,6,7,8-tetrahydrofolic acid as well as processes for their preparation. These ammonium salts may be separated into the single (6R) and (6S)-diastereoisomers. The separated diastereoisomers may be transformed into the corresponding alkali metal or alkaline earth metal salts.Type: GrantFiled: April 11, 1991Date of Patent: March 16, 1993Assignee: Sapec S.A. fine chemicalsInventors: Fabrizio Marazza, Jean Jacques
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Patent number: 5173488Abstract: Injectable aqueous compositions comprising folic acid and leucovorin and their salts, optionally including benzyl alcohol, sodium chloride and agents for adjusting pH are stabilized and buffered in the range of 6 to 10 by adding a combination of tromethamine and monothioglycerol. Such compositions remain stable for prolonged periods even when exposed to sunlight.Type: GrantFiled: May 1, 1991Date of Patent: December 22, 1992Assignee: American Cyanamid CompanyInventor: Bruce E. Haeger
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Patent number: 5145854Abstract: A 10-deaza-10-formyl folate analogue is a potent inhibitor of the enzyme glycinamide ribonucleotide formyltransferase and an antitumor agent. A typical embodiment is 10-formyl-5,8,10-trideazafolic acid (FTDF).Type: GrantFiled: November 27, 1991Date of Patent: September 8, 1992Inventors: Madhavan G. Nair, Shu W. Li
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Patent number: 5141941Abstract: Disclosed are a compound of the formula (I) or an acid addition salt thereof: ##STR1## wherein Q represents R.sup.1 , R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, n and z are defined as in the specification, preparation method thereof and fungicides containing the same.Type: GrantFiled: November 15, 1989Date of Patent: August 25, 1992Assignee: Ube Industries, Ltd.Inventors: Katsutoshi Fujii, Toshinobu Tanaka, Yasuhisa Fukuda
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Patent number: 5134235Abstract: Preparing (6S)-folinic acid and its salts, comprising recrystallization of alkaline-earth salts of (6R,S)-folinic acid and, where necessary, liberation of the acid from the alkaline-earth folinates and/or, where necessary, conversion into the alkali salts by at least one recrystallization in the presence of a base. Calcium-, magnesium-, potassium- and sodium-(6S)-folinates and (6S)-folinic acid are prepared.Type: GrantFiled: March 7, 1991Date of Patent: July 28, 1992Assignee: Eprova A.G.Inventors: Hans R. Mueller, Martin Ulmann, Josef Conti, Gunter Muerdel
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Patent number: 5124452Abstract: A method for preparing d,1-5-methyltetrahydrofolic acid and the salts thereof of the formula: ##STR1## wherein X is hydrogen, an alkaline metal or alkaline earth metal; by reduction of folic acid with sodium borohydride followed by the methylation of the tetrahydrofolic acid thus obtained with aqueous solutions of formaldehyde and sodium borohydride in an inert atmosphere.Type: GrantFiled: July 10, 1978Date of Patent: June 23, 1992Assignee: Bioresearch S.p.A.Inventor: Federico Gennari
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Patent number: 5047404Abstract: This invention relates to fused pyrimidine derivatives which have bronchodilator and anti-allergic activities. A compound of the invention is 2-(2-propoxyphenyl)pyrido[2,3-d]pyrimid-4(3H)-one.Type: GrantFiled: June 13, 1989Date of Patent: September 10, 1991Assignee: Smith Kline & French Laboratories, Ltd.Inventors: William J. Coates, Sean T. Flynn, Derek A. Rawlings
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Patent number: 5043446Abstract: A process of preparing l-biopterin is disclosed which comprises the steps of:Subjecting to selective Grignard reaction D-ribose having the hydroxyl groups in the 2- and 3-positions protected by an acetal group to give 6-deoxy-3,4-O-alkylidene allitol;subjecting the 1- and 2-positions of said allitol to oxidative cleavage to form 5-deoxy-2,3-O-alkylidene-L-ribose followed by deacetalization to give 5-deoxy-L-ribose;reacting 5-deoxy-L-ribose with a hydrazine compound to form a 5-deoxy-L-ribose hydrazone compound; andsubjecting said hydrazone compound to condensation reaction with an acid addition salt of 4-hydroxy-2,5,6-triaminopyrimidine followed by oxidation.Type: GrantFiled: February 23, 1990Date of Patent: August 27, 1991Assignee: Nisshin Flour Milling Co., Ltd.Inventors: Haruhiko Kikuchi, Kenji Mori
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Patent number: 5034393Abstract: Fungicidal compositions contain as active ingredient a 4-substituted-pyrido[3,2-d]pyrimidine, -pyrido[4,3-d]pyrimidine, -pyrido[3,4-d]pyrimidine, pyrido[2,3-d]pyrimidine, -pteridine, -pyrimido[4,5-d]pyrimidine, -pyrimido[4,5-c]pyridazine, -pyrimido[5,4-d]pyrimidine, -pyrimido[5,4-c]pyridazine, pyrimido[4,5-d]pyridazine, or -pyrimido[5,4-e]-1,2,4-triazine, for example 4-[2-(4-chlorophenyl)ethoxy]pyrido[2,3-d]pyrimidine.Type: GrantFiled: July 27, 1989Date of Patent: July 23, 1991Assignee: DowElancoInventors: Ronald E. Hackler, Glen P. Jourdan
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Patent number: 5026418Abstract: Pyrimidine compounds useful as plant growth regulators have the formula (I): ##STR1## wherein Y is an optionally substituted secondary or tertiary alkyl group containing from 3 to 7 carbon atoms or an optionally substituted cycloalkyl or alkylcycloalkyl group containing from 3 to 7 carbon atoms; R.sup.1 and R.sup.2, which may be the same or different, are hydrogen or a lower alkyl group; A is an optionally substituted heterocyclic group, for example thienyl or pyridyl; n is an integer which may be from 0 to 2 and is preferably 0; and R.sup.3 is hydrogen, an alkyl group containing from 1 to 4 carbon atoms, or an alkenyl or alkynyl group containing from 2 to 4 carbon atoms.Type: GrantFiled: February 20, 1990Date of Patent: June 25, 1991Assignee: Imperial Chemical Industries PLCInventor: Kevin R. Lawson
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Patent number: 5010194Abstract: A method for the resolution of (6R,S)-folinates into their diastereomers, comprising adding a water-soluble alkali metal, ammonium or alkaline earth metal salt of an inorganic or organic acid to an aqueous solution of a salt of (6R,S)-folinic acid, removing by filtration the salt which separates out, which consists predominantly of the corresponding (6R)-folinates, and isolating the desired (6S)-folinate from the filtrate.Type: GrantFiled: November 7, 1989Date of Patent: April 23, 1991Assignee: Eprova AGInventors: Hans R. Mueller, Martin Ulmann, Josef Conti, Guenter Muerdel
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Patent number: 5006655Abstract: For the preparation of 5,10-methenyl-(6R)-, 5-formyl-(6S)- or 5-methyl-(6S)-tetrahydrofolic acid or salts thereof, 5,10-methenyl-(6R,S)-tetrahydrofolic acid, the inner salt thereof or one of the salts thereof with strong acids is subjected to diastereomer separation by fractional crystallization and, if desired, the resulting 5,10-methenyl-(6R)-tetrahydrofolic acid is converted by treatment with a hydrolyzing agent into 5-formyl-(6S)-tetrahydrofolic acid or by treatment with a reducing agent into 5-methyl-(6S)-tetrahydrofolic acid, and the resulting free acid may be converted into one of its salts by treatment with a base.Type: GrantFiled: June 29, 1989Date of Patent: April 9, 1991Assignee: Eprova AGInventors: Hans R. Muller, Martin Ulmann, Josef Conti, Gunter Murdel
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Patent number: 4959472Abstract: The present invention related to the preparation of substantially pure diastereoisomers of derivatives of tetrahydrofolate and the use of such diastereoisomers. More particularly the present invention provides a process for the preparation of a desired substantially pure (6R or 6S) diastereoisomer of a derivative of tetrahydrofolic acid or salt or ester. The process comprises the steps of: attaching a chiral auxiliary group at either N-5 or N-10 of a mixture of 6R and 6S diastereoisomers of tetrahydrofolic acid, separating the new diastereoisomers, recovering the desired new diastereoisomer (6R or 6S) corresponding to the desired (6R or 6S) diastereoisomer, and converting the substantially pure new diastereoisomer recovered into the corresponding diastereoisomer.Type: GrantFiled: September 1, 1989Date of Patent: September 25, 1990Assignee: University of StrathclydeInventors: Hamish C. S. Wood, Colin J. Suckling, Lilias G. Rees
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Patent number: 4956461Abstract: A compound having the structure ##STR1## in which R.sub.1 is hydrogen or a lower alkyl group and R.sub.2 is hydrogen or methyl.Type: GrantFiled: August 24, 1989Date of Patent: September 11, 1990Assignee: Dana Farber Cancer Institute, Inc.Inventor: Andre Rosowsky
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Patent number: 4937342Abstract: The present invention relates to intermediates for synthesizing BH.sub.4 and derivatives thereof. The intermediates are shown as follows: ##STR1## wherein R.sub.1 is a hydrogen atom, alkyl, aralkyl, or aryl group; R.sub.2 is an alkyl, hydroxyalkyl, or polyhydroxyalkyl group; R.sub.3 and R.sub.4 are the same or different and represent alkyl, aralkyl, or aryl group; R.sub.5, R.sub.6, R.sub.7, and R.sub.8 are the same or different and represent a hydrogen atom or acyl group; R.sub.9 is an alkyl, aralkyl, or aryl group; R.sub.10 and R.sub.11 are the same or different and represent a hydrogen atom or acyl group; n is an integer of 5 or less; and HX is an acid. The invention also relates to a process for the preparation of L-biopterin.Type: GrantFiled: November 29, 1988Date of Patent: June 26, 1990Assignee: Kabushiki Kaisha Vitamin KenkyusyoInventors: Masayasu Kurono, Takehiko Susuki, Tomio Ogasawara, Nobuko Ohishi, Kunio Yagi
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Patent number: 4931442Abstract: This invention relates to a stabilized aqueous folic acid preparation which comprises a folic acid component selected from the group consisting of folic acid, ammonium, alkali metal and alkaline earth metal salts of folic acid and mixtures thereof, and which has an improved stability of its folic acid contents in the presence of oxygen, the said preparation containing as a stabilizer a combination of(a) at least one member selected from the group consisting of dihydrofolic acid and ammonium, alkali metal, alkaline earth metal and alkanolammonium salts thereof, and(b) at least one member selected from the group consisting of at least one hydroxypolycarboxylic acid and ammonium, alkali metal, alkaline earth metal and alkanolammonium salts thereof.Type: GrantFiled: December 6, 1988Date of Patent: June 5, 1990Inventor: Holger Blum
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Patent number: 4820706Abstract: 2,4-Diaminopteridine derivatives and the pharmaceutically acceptable salts thereof having potent anticancer activity are disclosed. The derivatives possess the structural formula: ##STR1## wherein Y is NH.sub.2, OH or SH, R is ##STR2## and X is ##STR3## in which R' is H or CH.sub.3 or ##STR4## in which R and R' are as previously defined, provided when Y is NH.sub.2, R' must be CH.sub.3 and when Y is OH, R' must be OH.Type: GrantFiled: January 27, 1986Date of Patent: April 11, 1989Assignee: Research CorporationInventors: M. Abu Khaled, Frederick Benington, Richard D. Morin
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Patent number: 4767859Abstract: Pteridine derivatives of general formula ##STR1## in which R is hydrogen or methyl, i.e.Type: GrantFiled: November 17, 1986Date of Patent: August 30, 1988Assignee: Rhone-Poulenc SanteInventor: Pierre Zimmermann
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Patent number: 4752573Abstract: The use of pterins to increase the activity of lymphokines and other cell growth factors, and a diagnostic or theraupeutic preparation that contains pterins combined with lymphokines. Adding pterins to lymphokines can increase the activity of the lymphokines by 3 to 5 times.Type: GrantFiled: April 8, 1986Date of Patent: June 21, 1988Assignees: Biotest-Serum-Institut GmbH, Gesellschaft fur Strahlen-und Umweltforschung mbHInventors: Irmgard Ziegler, Udo Schwulera, Hans Sonneborn
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Patent number: 4713454Abstract: (6R)-Tetrahydro-L-biopterin of the following formula: ##STR1## is prepared by catalytically reducing L-erythrobiopterin or an acyl derivative thereof in the presence of an amine, at pH 10-13 and with a platinum-base catalyst and when one or more acyl groups still remain, then removing the acyl groups. (6R)-Tetrahydro-L-biopterin is effective for the treatment of certain serious neuroses and malignant hyperphenylalaniemia. The present invention has succeeded in preparing (6R)-tetrahydro-L-biopterin at a high asymmetric ration R/S and moreover with a high yield. Since the process of this invention makes use of an amine as a base, the process is free from admixture of any inorganic salt and can hence provide high-purity crystals with ease.Type: GrantFiled: January 23, 1986Date of Patent: December 15, 1987Assignees: Shiratori Pharmaceutical Co., Ltd., Suntory LimitedInventors: Hideaki Sakai, Tadashi Kanai
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Patent number: 4701455Abstract: This invention provides the pterin compounds of formula (I) and use in human and veterinary medicine. ##STR1## wherein R represents lower alkyl groups (straight or branched) of 1-8 carbons (for this formula and all other formulas herein) including all stereo isomers thereof or a pharmaceutically acceptable salt thereof.Type: GrantFiled: June 21, 1985Date of Patent: October 20, 1987Assignee: Burroughs Wellcome Co.Inventors: Charles A. Nichol, John F. Reinhard, Jr., Gary K. Smith, Eric C. Bigham
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Patent number: 4665176Abstract: A process for the preparation of 5,6,7,8-tetrahydrofolic acid which comprises dissolving and/or suspending folic acid or dihydrofolic acid in an aqueous solution containing an inorganic base, and bringing the resulting solution or suspension into contact with hydrogen in the presence of a noble metal catalyst while maintaining its pH at 5-9, thereby catalytically hydrogenating the folic acid of dihydrofolic acid into 4,5,6,7-tetrahydrofolic acid.Type: GrantFiled: October 10, 1985Date of Patent: May 12, 1987Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Yutaka Hirai, Masaaki Torisu, Eri Nagayoshi
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Patent number: 4665182Abstract: The compounds of formula (I) ##STR1## wherein R.sup.1 is hydrogen, lower alkyl of 1-4 carbons, lower alkenyl of 2-4 carbons, --B--X--R.sup.5).sub.n, or --B--Z--B--X--R.sup.5 --.sub.n ; n=0 when X is halogen or n=1 when X is --O--, --NR.sup.6 -- (where R.sup.6 is hydrogen or lower alkyl of 1-4 carbons) or --S(O)q-- (where q=0 to 2); B is lower alkanyl (straight or branched) of 1-5 carbons; R.sup.5 is hydrogen, aralkyl of 7 to 12 carbons or alkyl of 1-10 carbons; Z is --O--, NR.sup.6 --, or --S(O)q--; R.sup.2 is hydrogen or lower alkyl of 1-4 carbons or lower alkenyl of 2-4 carbons or either R.sup.1 and R.sup.2 together with the carbon atom in the pteridine ring structures to which they are attached, form a spirocycloalkyl ring system having 3 to 7 carbon atoms; R.sup.3 and R.sup.4 are hydrogen or methyl; R.sup.2 and R.sup.3, together with the carbon atoms in the pteridine ring structure to which they are attached, form a cycloalkyl ring system having 5 to 7 carbon atoms; provided that at least one of R.sup.Type: GrantFiled: November 19, 1985Date of Patent: May 12, 1987Assignee: Burroughs Wellcome Co.Inventors: Charles A. Nichol, John F. Reinhard, Jr., Gary K. Smith, Eric C. Bigham
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Patent number: 4649197Abstract: A sulfate of tetrahydrobiopterin having the formula (I): ##STR1## and a process for preparing the same, which comprises crystallizing tetrahydrobiopterin from an aqueous medium containing sulfuric acid.Type: GrantFiled: March 18, 1985Date of Patent: March 10, 1987Assignee: Kanegafuchi Kagaku Kogyo KabushikiInventors: Hayashi Uchino, Masaaki Azuma, Takehisa Ohashi, Kiyoshi Watanabe
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Patent number: 4628090Abstract: A methotrexate derivative having the following general formula is incapable of forming polyglutamate and thus is expected to have reduced cytotoxicity associated with the formation of polyglutamate derivatives in a living cell, ##STR1## wherein n is from 0 to 5.Type: GrantFiled: August 19, 1985Date of Patent: December 9, 1986Assignee: Rensselaer Polytechnic InstituteInventor: James K. Coward
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Patent number: 4595752Abstract: A process for preparing tetrahydrobiopterin which is rich in the (6R)-form, which comprises hydrogenating L-erythrobiopterin in a basic medium in the presence of a platinum group catalyst. According to the process, tetrahydrobiopterin improved in (6R)/(6S) ratio can be easily obtained in the high yield.Type: GrantFiled: February 21, 1985Date of Patent: June 17, 1986Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Masaaki Azuma, Takehisa Ohashi, Kiyoshi Watanabe
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Patent number: 4587340Abstract: This invention provides the intermediates of formula II-A below, useful to make the pterin compounds of formula I below. The pterin compounds are used in human and veterinary medicine. ##STR1## wherein R represents a lower alkyl of 1 to 8 carbons.Type: GrantFiled: June 13, 1984Date of Patent: May 6, 1986Assignee: Burroughs Wellcome Co.Inventors: Charles A. Nichol, John F. Reinhard, Jr., Gary K. Smith, Eric C. Bigham
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Patent number: 4584375Abstract: A methotrexate derivative having the following general formula is incapable of forming polyglutamate and thus is expected to have reduced cytotoxicity associated with the formation of polyglutamate derivatives in a living cell, ##STR1## wherein n is from 0 to 5.Type: GrantFiled: August 21, 1984Date of Patent: April 22, 1986Assignee: Rensselaer Polytechnic InstituteInventor: James K. Coward
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Patent number: 4572910Abstract: 1,2,4-Triazolo[1,5-c]pyrimidines substituted at the 5 or 7 positions through a nitrogen atom which is part of a heterocyclic ring have been found to have potent bronchodilator activity. Methods for inducing bronchodilation, pharmaceutical compositions and synthetic processes are also disclosed.Type: GrantFiled: March 3, 1983Date of Patent: February 25, 1986Assignee: Riker Laboratories, Inc.Inventor: James J. Wade
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Patent number: 4572908Abstract: Dihydropyridine anti-ischaemic agents of the formula: ##STR1## and their salts where R is aryl or heteroaryl, R.sup.1 and R.sup.2 are each C.sub.1 -C.sub.4 alkyl or 2-methoxyethyl, Y is --(CH.sub.2).sub.n -- where n is 2, 3, or 4 and is optionally substituted by 1 or 2 CH.sub.3 groups, and R.sup.3 is an optionally substituted 5- or 6-membered heterocyclic group attached to the adjacent N atom by a C atom, said group R.sup.3 being optionally fused to a further heterocyclic group or to a benzene ring.Type: GrantFiled: December 16, 1983Date of Patent: February 25, 1986Assignee: Pfizer Inc.Inventors: Simon F. Campbell, Peter E. Cross, John K. Stubbs, John E. Arrowsmith
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Patent number: 4540783Abstract: A novel compound, 1',2'-diacyl-(6R,S)-5,6,7,8-tetrahydro-L-biopterin which is prepared by catalytical hydrogenation of a 1',2'-diacyl-L-biopterin in a solvent in the presence of a catalyst. The 1',2'-diacyl-L-biopterin is prepared from a 1,1-dialkylsulfonyl-L-rhamnose through an acyl derivative of 5-deoxy-L-arabinose and a hydrazine derivative of tetrahydro-L-biopterin without isolating the intermediate products. The 1', 2'-diacyl-(6R,S)-5,6,7,8-tetrahydro-L-biopterin can be used for treatment of atypical phenylketonuria or dihydropterin-reductase deficiency and can readily cross the blood brain barrier without neurotransmitter precursors.Type: GrantFiled: November 15, 1982Date of Patent: September 10, 1985Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventor: Max Viscontini
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Patent number: 4509972Abstract: Compounds of the formula ##STR1## wherein R, R.sub.1, R.sub.2 and R.sub.3 are substituents of diverse types, and salts thereof. The compounds as well as their salts are useful as herbicides.Type: GrantFiled: March 28, 1983Date of Patent: April 9, 1985Assignee: Celamerck GmbH & Co. KGInventors: Rudolf Mengel, Ludwig Schroder, Werner Stransky, Gerbert Linden, Gerhart Schneider, Sigmund Lust
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Patent number: 4500711Abstract: In the synthesis of calcium leucovorin (calcium 5-formyl-5,6,7,8-tetrahydrofolate), the use of an amine base in the conversion of anhydroleucovorin (5,10-methenyl-5,6,7,8-tetrahydrofolic acid) to leucovorin unexpectedly results in a pure (USP) product directly from the reaction mixture.Type: GrantFiled: December 22, 1980Date of Patent: February 19, 1985Assignee: Burroughs Wellcome Co.Inventors: James C. Wisowaty, Roy A. Swaringen, David A. Yeowell