Nitrogen Bonded Directly To The Pteridine Ring System Patents (Class 544/258)
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Publication number: 20040029885Abstract: The present invention relates to new dihydropteridinones of the formula (I) 1Type: ApplicationFiled: August 23, 2002Publication date: February 12, 2004Applicant: Boehringer Ingelheim Pharma KGInventors: Eckhart Bauer, Steffen Breitfelder, Christian Eickmeier, Matthias Grauert, Matthias Hoffmann, Thorsten Lehmann-Lintz, Gerald Pohl, Jens Quant, Norbert Redemann, Gisela Schnapp, Martin Steegmaier
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Publication number: 20030186987Abstract: Described are heterocyclic pyrimidine derivatives and a method of inhibiting epidermal growth factor by treating, with an effective inhibiting amount, a mammal, in need thereof, a compound of the formula: 1Type: ApplicationFiled: July 24, 2002Publication date: October 2, 2003Inventors: Alexander James Bridges, William Alexander Denny, David Fry, Alan Kraker, Robert Frederick Meyer, Gordon William Rewcastle, Andrew Mark Thompson
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Publication number: 20030149047Abstract: The invention provides compounds of general formula (I) wherein Q, R, R1, R4, R5, R6, R7 and R8 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.Type: ApplicationFiled: October 21, 2002Publication date: August 7, 2003Inventors: Tomas Eriksson, Peter Hansen, Martin Hemmerling, Krister Henriksson, Tomas Klingstedt, Lars Pettersson, Michael Bodkin
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Patent number: 6596721Abstract: Pure and extremely stable crystalline (6R)-tetrahydrofolic acids, absolutely inert even when exposed to air and elevated temperature without stabilizers being added, are prepared by a crystallization process at a pH of ≧2.Type: GrantFiled: January 8, 2001Date of Patent: July 22, 2003Assignee: Eprova AGInventors: Hans Rudolf Müller, Martin Ulmann, Rudolf Moser, Thomas Ammann
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Publication number: 20030130286Abstract: Disclosed are compounds of Formulae (Ia), (Ib), (Ic), (Id) wherein: W is NH, S, SO, or SO2; R2 is (un)substituted aryl, (un)substituted heteroaryl, or (un)substituted carbocycle or heterocycle; Q is hydrogen or lower alkyl; R4 and R6 are the same or different and represent hydrogen, halogen, lower alkyl, lower alkoxy, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted arylalkyl or (un)substituted heteroarylalkyl; and R8 is hydrogen, lower alkyl or an (un)substituted carbocyclic group containing from 3-7 members, up to two of which members are optionally hetero atoms selected from oxygen and nitrogen; or R8 is (un)substituted aryl, (un)substituted heteroaryl, (un)substituted arylalkyl or (un)substituted heteroarylalkyl. These compounds are useful for treating cell proliferative disorders, such as cancer and restenosis. These compounds are potent inhibitors of cyclin-dependent kinases (cdks) and growth factor-mediated kinases.Type: ApplicationFiled: March 6, 2002Publication date: July 10, 2003Inventors: William Alexander Denny, Gordon William Rewcastle, Ellen Dobrusin, James Bernard Kramer, Dennis Joseph McNamara, Howard Daniel Hollis Showalter, Peter Laurence Toogood
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Patent number: 6521620Abstract: Described are heterocyclic pyrimidine derivatives and a method of inhibiting epidermal growth factor by treating, with an effective inhibiting amount, a mammal, in need thereof, a compound of the formula: where: at least two of A-E are nitrogen, with the remaining atom(s) carbon; X=NH or NR7, such that R7=lower alkyl (1-4 carbon atoms), OH, NH2, lower alkoxy (1-4 carbon atoms) or lower monoalkylamino (1-4 carbon atoms); n=0, 1, 2. The remaining substituents are described in detail in the specification.Type: GrantFiled: October 30, 1998Date of Patent: February 18, 2003Assignee: Warner-Lambert CompanyInventors: Alexander James Bridges, William Alexander Denny, David Fry, Gordon William Rewcastle
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Patent number: 6511990Abstract: The present invention provides the compound having the formula: wherein each of R1 and R2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH2—; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.Type: GrantFiled: August 24, 2000Date of Patent: January 28, 2003Assignees: Sloan-Kettering Institute for Cancer Research, The Trustees of Columbia University in the City of New YorkInventors: Ronald Breslow, Sandro Belvedere, Leland Gershell, Thomas A. Miller, Paul A. Marks, Victoria M. Richon, Richard A. Rifkind
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Patent number: 6500829Abstract: 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: April 18, 1995Date of Patent: December 31, 2002Assignee: University of StrathclydeInventors: Hamish Christopher Swan Wood, Colin James Suckling, Lilias G. Rees
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Patent number: 6476031Abstract: The invention is directed to methods to inhibit TGF-&bgr; and/or p38-&agr; kinase using compounds of the formula or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar′ is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.Type: GrantFiled: August 27, 1999Date of Patent: November 5, 2002Assignee: Scios, Inc.Inventors: Sarvajit Chakravarty, Sundeep Dugar, John J. Perumattam, George F. Schreiner, David Y. Liu, John A. Lewicki
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Patent number: 6441168Abstract: This invention relates to stable crystalline salts of 5-methyl-(6R,S)-, -(6S)- and -(6R)-tetrahydrofolic acid, to methods of producing these salts and to the use thereof use as a constituent for the production of drugs or as a food additive, and to preparations containing these salts.Type: GrantFiled: April 17, 2000Date of Patent: August 27, 2002Assignee: Eprova AGInventors: Rudolf Müller, Rudolf Moser, Thomas Egger
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Patent number: 6413724Abstract: The invention provides chemistry libraries containing fused 2,4-pyrimidinediones. The invention also provides methods for the construction of fused 2,4-pyrimidinedione containing libraries. The invention further provides methods for the identification of bioactive, fused 2,4-pyrimidinediones from those libraries.Type: GrantFiled: February 4, 1997Date of Patent: July 2, 2002Assignee: Versicor, Inc.Inventors: Mikhail F. Gordeev, Dinesh V. Patel
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Patent number: 6399609Abstract: Corticotropin releasing factor (CRF) antagonists of formula I: and their use in treating anxiety, depression, and other psychiatric and neurological disorders.Type: GrantFiled: May 11, 2000Date of Patent: June 4, 2002Assignee: Bristol-Myers Squibb Pharma CompanyInventor: Richard Gerald Wilde
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Publication number: 20020049163Abstract: Oligonucleotide-folate conjugates are described wherein folates are conjugated to one or more sites on an oligonucleotide including the 2′-, 3′-, 5′-, nucleobase and internucleotide linkage sites. The folate can be attached via the &agr;- or &ggr;-carboxylate, optionally through a linking group. Methods for the regiospecific synthesis of the conjugates are diclosed. Also disclosed are nucleosidic and non-nucleosidic linkers conjugated to folic acid and related folates.Type: ApplicationFiled: October 9, 2001Publication date: April 25, 2002Applicant: ISIS Pharmaceuticals, Inc.Inventors: Phillip Dan Cook, Muthiah Manoharan, Balkrishen Bhat, Andrel P. Guzzev
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Patent number: 6358953Abstract: Disclosed are novel metal pterin and pterin analog complexes and compositions useful as antineoplastic and antiviral agents.Type: GrantFiled: October 21, 1999Date of Patent: March 19, 2002Inventor: Phillip B. B. Moheno
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Patent number: 6291673Abstract: Novel folic acid derivatives and their use in preparation of &ggr;-esters of folic acid via a pteroyl azide intermediate are described. Folic acid &ggr;-esters are useful intermediates in the synthesis of folic acid conjugates capable of binding folate receptors in vitro and in vivo.Type: GrantFiled: April 17, 2000Date of Patent: September 18, 2001Assignee: Purdue Research FoundationInventors: Philip L. Fuchs, Jin Luo, Douglas A. Lantrip
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Patent number: 6271374Abstract: Pure and extremely stable crystalline (6S)- and (6R)-tetrahydrofolic acids, absolutely inert even when exposed to air and elevated temperature without stabilizers being added, are prepared by a crystallization process at a pH of ≧3.5 for the preparation of crystalline (6S)-tetrahydrofolic acid and at a pH of ≧2 for the preparation of crystalline (6R)-tetrahydrofolic acid.Type: GrantFiled: January 26, 1998Date of Patent: August 7, 2001Assignee: Eprova AGInventors: Hans Rudolf Müller, Martin Ulmann, Rudolf Moser, Thomas Ammann
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Publication number: 20010007867Abstract: This invention relates to compounds of the formula 1Type: ApplicationFiled: December 13, 1999Publication date: July 12, 2001Inventor: YUHPYNG L. CHEN
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Publication number: 20010002398Abstract: Pure and extremely stable crystalline (6S)- and (6R)-tetrahydrofolic acids, absolutely inert even when exposed to air and elevated temperature without stabilizers being added, are prepared by a crystallization process at a pH of ≧3.5 for the preparation of crystalline (6S)-tetrahydrofolic acid and at a pH of ≧2 for the preparation of crystalline (6R)-tetrahydrofolic acid.Type: ApplicationFiled: January 8, 2001Publication date: May 31, 2001Applicant: EPROVA AKTIENGESELLSCGAFTInventors: Hans Rudolf Muller, Martin Ulmann, Rudolf Moser, Thomas Ammann
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Patent number: 6166019Abstract: Compounds of Formula I and II and their pharmaceutically acceptable, salts, esters and prodrugs thereof are selective alpha-1D adrenoceptor anatagonists and may be useful for treating disease states.Type: GrantFiled: July 9, 1999Date of Patent: December 26, 2000Assignee: Abbott LaboratoriesInventors: Michael D. Meyer, William A. Caroll
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Patent number: 6162914Abstract: The inventive process for the reduction of pterins by means of an alkali metal boron hydride in water to the corresponding 5,6,7,8-tetrahydropterins is characterized in that the reduction is carried out in the presence of a catalytical amount of a water-soluble Pb(II)-salt.Type: GrantFiled: May 7, 1999Date of Patent: December 19, 2000Assignee: Cerbios-Pharma S.A.Inventors: Nando Toderi, Fabrizio Marazza
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Patent number: 6162806Abstract: An active oxygen scavenger comprising as an active ingredient a pterin derivative of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are independently a hydrogen atom, an alkyl group of 1 to 4 carbon atoms, or an acyl group of the formula R.sup.3 --CO--, R.sup.3 is an alkyl group of 1 to 4 carbon atoms, X is a formyl group or hydroxymethyl group, A is a group of the formula (Ia): ##STR2## and n is 0 or an integer of 1 or more, with the proviso that when X is a hydroxymethyl group, n is 0, or when n is an integer of 1 or more, each of R.sup.1 and R.sup.2 is a hydrogen atoms, and X is a formyl group, or a cyclic compound thereof, or a salt thereof is disclosed.Type: GrantFiled: March 31, 1998Date of Patent: December 19, 2000Assignee: Artemis, Inc.Inventors: Toshiyuki Arai, Keisuke Makino, Kenjiro Mori
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Patent number: 6160116Abstract: 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, 1995Date of Patent: December 12, 2000Assignee: Eprova A.G.Inventors: Hans Rudolf Mueller, Martin Ulmann, Josef Conti, Gunter Muerdel
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Patent number: 6156766Abstract: Benzamide compounds of the formula ##STR1## wherein each symbol is defined in the specification, isomers thereof and pharmaceutically acceptable acid addition salts thereof. Pharmaceutical compositions comprising a therapeutically effective amount of this compound and a pharamaceutically acceptable additive, and therapeutic agents for hypertension, therapeutic agents for angina pectoris, therapeutic agent for asthma, therapeutic agents for renal and peripheral circulatory disturbances and inhibitor of cerebral vasospasm, which comprise this compound. The compound of the present invention has strong smooth muscle relaxing action, and shows hypertensive action and cerebral.cndot.coronary vasodilating action like conventional calcium antagonists, as well as long-lasting renal and peripheral circulation improving action.Type: GrantFiled: February 18, 1999Date of Patent: December 5, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Masafumi Arita, Tadamasa Saitoh, Masanori Minoguchi, Keiji Yamagami, Hiroyuki Satoh
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Patent number: 6140325Abstract: Thienopyrimidine derivatives are disclosed. Also disclosed are methods for the production and use of these compounds.Type: GrantFiled: September 30, 1996Date of Patent: October 31, 2000Assignee: Takeda Chemical Industries, Ltd.Inventors: Shuichi Furuya, Nobuo Choh, Tetsuya Ohtaki, Toshifumi Watanabe
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Patent number: 6110931Abstract: There are disclosed compounds of formula (I) ##STR1## and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.Type: GrantFiled: March 25, 1999Date of Patent: August 29, 2000Assignee: Merck & Co., Inc.Inventors: Thomas F. Walsh, Mark T. Goulet, Feroze Ujjainwalla, Jonathan R. Young
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Patent number: 6083948Abstract: Corticotropin releasing factor (CRF) antagonists of formula I: and their use in treating anxiety, depression, and other psychiatric and neurological disorders are disclosed.Type: GrantFiled: May 16, 1997Date of Patent: July 4, 2000Assignee: Dupont Pharmaceuticals CompanyInventor: Richard Gerald Wilde
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Patent number: 6066638Abstract: Compounds of Formula I, and their N-oxides and agriculturally suitable salts, are disclosed which are useful as fungicides ##STR1## wherein W is O, S(O).sub.n or NR.sup.5 ;n is 0, 1 or 2;Q is O or S;G is a fused phenyl, naphthalene, thiophene, furan, pyrrole, pyridine, thiazole, oxazole, imidazole, pyrazine, pyridazine or pyrimidine ring; andR.sup.1 -R.sup.5 are as defined in the disclosure.Also disclosed are compositions containing the compounds of Formula I and a method for controlling plant diseases caused by fungal plant pathogens which involves applying an effective amount of a compound of Formula I.Type: GrantFiled: January 2, 1998Date of Patent: May 23, 2000Assignee: E. I. du Pont de Nemours and CompanyInventors: James Francis Bereznak, Zen-Yu Chang, Charlene Gross Sternberg
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Patent number: 5994321Abstract: A series of guanine analogs and physiological salts thereof, which are useful as virus inhibitors and as antiviral agents in the treatment of viral disease, having the basic structures of: ##STR1## wherein B is H, CH.sub.3 or NH.sub.2 ; C is NH.sub.2 or SCH.sub.3 ; D is N or CH; E is O, S or Se; and G is selected from a group consisting of alkanes, alkenes, ethers, esters, hydrocarbons, amines and heterocyclic compounds, is herein disclosed. In I and III, A is O, S or Se while in II, A is NH.sub.2, OH, NHOH, OCH.sub.3 or SCH.sub.3. In I and II, F is 0, S or Se, while in III, F is F is 0, S, Se or NH. These compounds may be formulated with a physiological carrier, and used either alone or in combination with, for example, acyclovir or ganciclovir or another therapeutic agent, for the treatment of conditions resulting from viral infections.Type: GrantFiled: June 10, 1997Date of Patent: November 30, 1999Assignee: Aronex Pharmaceuticals, Inc.Inventors: Arthur F. Lewis, Ganapathi R. Revankar
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Patent number: 5902810Abstract: The present invention relates to the use of pteridine derivatives of the formula I ##STR1## in which X is O, NH or N--(C.sub.1-C.sub.5)-alkanoyl, R.sup.3 is the radical --OR.sup.4, --NR.sup.5 R.sup.6 or --S(O).sub.m R.sup.7, and R, R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and m have the meanings given in claim 1, which are nitric oxide synthase inhibitors, for the treatment of diseases which are caused by an increased nitric oxide level.Type: GrantFiled: February 18, 1997Date of Patent: May 11, 1999Assignee: Hoechst AktiengesellschaftInventors: Wolfgang Pfleiderer, Harald Schmidt, Rainer Henning
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Patent number: 5874433Abstract: Inhibitor of the use of tetrahydrobiopterin as a cofactor for nitric oxide synthase, e.g., substituted 4-phenyl(hydropyridines) such as 1-methyl-4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine or, 4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine) or tetrahydropterin analog which does not replace tetrahydrobiopterin as a substrate for nitric oxide synthase such as (6R,S)-6,7-dimethyl-tetrahydropterin or (6R,S)-tetrahydrofolic acid or 2,4-diamino-, 2,6-diamino, or 4,6-diamino mono- or disubstituted pyrimidines or the corresponding pyrimidine-3-oxides such as 2,4-diamino-6-(diethylamino)pyrimidine, 2,4-diamino-6-piperidino-pyrimidine-3-oxide, 2,4-diamino-6-hydroxypyrimidine, 4,6-diamino-2-hydroxypyrimidine or 2,5-diamino-4,6-dihydroxypyrimidine is administered to inhibit nitric oxide synthesis from arginine in vascular cells in a subject in need of such inhibition (e.g., for prophylaxis or treatment of cytokine- or endotoxin-induced hypotension (e.g., septic shock).Type: GrantFiled: December 19, 1995Date of Patent: February 23, 1999Assignee: Cornell Research Foundation, Inc.Inventor: Steven S. Gross
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Patent number: 5869665Abstract: Novel quinazolinone derivatives with good binding affinity for the CCK-A and CCK-B receptors, pharmaceutical compositions containing them, methods of using them and a novel process for their preparation are taught. The compounds are useful agents to suppress appetite, reduce gastric acid secretion, and the like.Type: GrantFiled: April 8, 1997Date of Patent: February 9, 1999Assignee: Warner-Lambert CompanyInventor: Janak Khimchand Padia
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Patent number: 5817659Abstract: This invention relates to stable crystalline salts of (6R,S)-, (6S)- and (6R)-tetrahydrofolic acid, to methods of preparing these salts and to their use as an ingredient for the production of drugs and pharmaceutical preparations.Type: GrantFiled: November 7, 1996Date of Patent: October 6, 1998Assignee: Eprova AGInventors: Hans R. Muller, Martin Ulmann, Rudolf Moser, Thomas Ammann
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Patent number: 5814635Abstract: A concentrated, stable solution, especially an injection solution, which comprises water and either sodium-leucovorin or potassium-leucovorin or sodium-N(5)-methyl-5,6,7,8-tetrahydrofolic acid or potassium-N(5)-methyl-5,6,7,8-tetrahydrofolic acid. Also described is a process for the preparation of the solution, as well as its uses.Type: GrantFiled: July 2, 1997Date of Patent: September 29, 1998Assignee: Cerbios-Pharma S.A.Inventors: Peter Buchs, Fabrizio Marazza
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Patent number: 5807854Abstract: Compounds of general formula I and their salts and solvates are antifungal agents and as such are useful in the treatment of various fungal infections. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.Type: GrantFiled: March 31, 1997Date of Patent: September 15, 1998Assignee: J. Uriah & Cia. S.A.Inventors: Javier Bartroli, Enric Turmo, Manuel Anguita
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Patent number: 5776942Abstract: A rapid-acting remedy for asthma having a bronchodilating action contains at least one pyrido?2,3-d!pyrimidine derivative represented by the general formula (A) or pharmaceutically acceptable salts or metal complexes thereof as an effective component: ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and each of R.sup.1 and R.sup.2 is hydrogen, alkyl or benzyl; R.sup.3 is hydrogen, hydroxyl, dialkylaminomethyleneamino or --NH--X; X is hydrogen, alkyl, alkenyl, hydroxyl, amino, hydroxyalkyl, benzyl or acyl; R.sup.4 is hydrogen, alkyl, halogen, nitro, amino, hydroxyl, benzyloxy, cyano, carboxyl, alkoxycarbonyl, alkoxysulfonyl, aminosulfonyl, dialkylaminosulfonyl or sulfo; and R.sup.5 is hydrogen, alkyl or amino. The rapid-acting remedy for bronchial asthma is capable of relieving the symptom of laboring breath at the onset of asthma due to its excellent bronchodilating action.Type: GrantFiled: June 14, 1995Date of Patent: July 7, 1998Assignee: Nippon Zoki Pharmaceutical Co., Ltd.Inventors: Kazuhito Furukawa, Taisuke Hasegawa
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Patent number: 5756502Abstract: Novel quinazolinone derivatives with good binding affinity for the CCK-A and CCK-B receptors, pharmaceutical compositions containing them, methods of using them and a novel process for their preparation are taught. The compounds are useful agents to suppress appetite, reduce gastric acid secretion, and the like.Type: GrantFiled: July 10, 1995Date of Patent: May 26, 1998Assignee: Warner-Lambert CompanyInventor: Janak Khimchand Padia
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Patent number: 5710271Abstract: A process for the preparation, separation and purification of (6S) and (6R) diastereomers of folinic acid salts with at least dibasic amines is disclosed, which process comprises the hydrolysis of (6RS)-5,10-methenyl-5,6,7,8-tetrahydrofolic acid chloride hydrochloride with an at least dibasic amine and the subsequent separation of the diasteromeric salts.Type: GrantFiled: June 7, 1995Date of Patent: January 20, 1998Assignee: Dibra S.p.A.Inventors: Ernst Felder, Giorgio Ripa, Carlo Distaso
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Patent number: 5698408Abstract: Pterin derivatives having the general formula I ##STR1## wherein R.sub.1 represents a group --(CHOH).sub.2 --CH.sub.3 or --(CHOH).sub.2 --CH.sub.2 OH,R.sub.2 and R.sub.3 are not the same and represent either hydrogen or the group --(CH.sub.2).sub.3 CONH(CH.sub.2).sub.4 --NH--R.sub.4, wherein R.sub.4 represents hydrogen or a usual label group for immunoassays or usual coating/support materials for solid phase immunoassays or immunogenic groups for the preparation of antibodiesare useful for the preparation of sensitive immunoassays for the determination of neopterin and biopterin.Type: GrantFiled: November 2, 1995Date of Patent: December 16, 1997Assignee: B.R.A.H.M.S. Diagnostica GmbHInventor: Hartmut Rokos
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Patent number: 5698693Abstract: A method for resolving 5,6,7,8-tetrahydrofolic acid derivatives into diastereomerically pure 6R and 6S forms. The method comprises (1) alpha esterification of the tetrahydrofolic acid derivative; (2) resolution of the alpha monoester into pure diastereomer; and (3) deprotecting the resolved alpha monoester to thereby produce the pure diastereomer of the original 5,6,7,8 tetrahydrofolic acid derivative. The resolution step can be carried out by any conventional means including chromatography or fractional crystallization. The method results in absolute diastereomeric purity even when an achiral stationary phase is used for the resolution.Type: GrantFiled: November 16, 1992Date of Patent: December 16, 1997Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Anthony L. Fitzhugh, Rhone K. Akee
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Patent number: 5696264Abstract: Disclosed are novel folic acid-alkaline phosphatase conjugates useful in a competitive immunoassay for folic acid in a biological fluid such as serum. A preferred conjugate involves a folate hapten bound to (N-Succinimidyl?4-iodoacetyl!aminobenzoate) through a 1,12-diamino-4,9-dioxadodecanyl spacer arm.Type: GrantFiled: June 21, 1996Date of Patent: December 9, 1997Assignee: Bayer CorporationInventors: James P. Albarella, Linda M. Anderson-Mauser, Frank Thomas Hartl, Gary M. Johnson
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Patent number: 5693641Abstract: This invention is directed to bicyclic pyrimidine derivatives which are useful as anti-coagulants. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat disease-states characterized by thrombotic activity.Type: GrantFiled: August 16, 1996Date of Patent: December 2, 1997Assignee: Berlex Laboratories Inc.Inventors: Brad O. Buckman, Raju Mohan, Michael M. Morrissey
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Patent number: 5693771Abstract: In accordance with this invention novel compounds are provided that are selected from saturated and unsaturated pyrans and furans substituted with at least a phosphonate group and a heterocyclic base. These compounds are useful as antiinfectives, flame retardants, diagnostic oligonucleotides and immunogens.Type: GrantFiled: March 13, 1996Date of Patent: December 2, 1997Assignee: Gilead Sciences, Inc.Inventors: Petr Alexander, Ernest J. Prisbe
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Patent number: 5660835Abstract: A method of treating adenosine depletion in a subject in need of such treatment is disclosed. The method comprises administering to the subject folinic acid or a pharmaceutically acceptable salt thereof in an amount effective to treat adenosine depletion. A method of treating asthma in a subject in need of such treatment is also disclosed. The method comprises administering to the subject dehydroepiandrosterone, analogs thereof, or pharmaceutically acceptable salts thereof in an amount effective to treat asthma.Type: GrantFiled: February 24, 1995Date of Patent: August 26, 1997Assignee: East Carolina UniversityInventor: Jonathan W. Nyce
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Patent number: 5599931Abstract: The (6S) stereoisomer of folinic acid is obtained in high optical purity by salification of (R,S) folinic acid with di- or polyamines and subsequent selective crystallization of the desired diasteromeric salt.Type: GrantFiled: June 1, 1995Date of Patent: February 4, 1997Assignee: Bracco S.p.A.Inventors: Giorgio Ripa, Rodolfo Piva, Ernst Fekder
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Patent number: 5521182Abstract: The cyclic amide derivative is defined by the formula (I) or a salt thereof:R.sup.1 --(CH.sub.2).sub.n --Zin whichR.sup.1 is a group derived from a cyclic amide compound, substituted or unsubstituted, n is zero or an integer of 1 to 10 and Z is ##STR1## R.sup.2 being an aryl, a substituted aryl, a cycloalkyl or a heterocyclic group, m being an integer of 1 to 6, R.sup.3 being hydrogen or a lower alkyl, R.sup.4 being an aryl or a substituted aryl, a cycloalkyl or a heterocyclic group, p being an integer of 1 to 6, provided that the cyclic amide compound is quinazoline-on or quinazoline-dion, R.sup.2 and R.sup.4 are neither aryl nor substituted aryl. The cyclic amide compound is pharmacologically effective to prevent and treat diseases due to insufficiency of the central choline functions.Type: GrantFiled: May 25, 1995Date of Patent: May 28, 1996Assignee: Eisai Co., Ltd.Inventors: Hachiro Sugimoto, Masahiro Yonaga, Norio Karibe, Youichi Iimura, Satoshi Nagato, Atsushi Sasaki, Yoshiharu Yamanishi, Hiroo Ogura, Takashi Kosasa, Kumi Uchikoshi, Kiyomi Yamatsu
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Patent number: 5521181Abstract: The present invention relates to a compound of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein W is a bicyclic heterocyclic ring system. The compounds are .alpha.-1 adrenergic antagonists and are useful in the treatment of BPH; also disclosed are .alpha.-1 antagonist compositions and a method for antagonizing .alpha.-1 receptors and treating BPH.Type: GrantFiled: January 27, 1995Date of Patent: May 28, 1996Assignee: Abbott LaboratoriesInventors: Michael D. Meyer, Robert J. Altenbach, William A. Carroll, Irene Drizin, Suzanne A. Lebold, Edmund L. Lee, Kevin B. Sippy, Karin R. Tietje, Diane M. Yamamoto, James F. Kerwin, Jr.
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Patent number: 5489684Abstract: (6S)-THF is obtained by adding, in portions, an acid to an aqueous solution of a (6RS)-diastereoisomeric mixture of an alkali metal salt of 5,6,7,8-tetrahydrofolic acid. The addition is made at a temperature from 5.degree. C. to 80.degree. C. for the purpose of the selective crystallization for a period sufficient to stabilize the pH to a value of from 4.8 to 5.3. Then, the formed solid, i.e., (6S)-5,6,7,8-tetrahydrofolic acid, is separated.Type: GrantFiled: December 1, 1993Date of Patent: February 6, 1996Assignee: Sapec S.A. Fine ChemicalsInventors: Pascal Jequier, Fabrizio Marazza
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Patent number: 5457202Abstract: A process for preparing (6S)-5-methyltetrahydrofolic acid by resolution of racemic (6R,S)-5-methyltetrahydrofolic acid using a base, wherein the base is N-ethyl-2-aminomethylpyrrolidine or its optical isomers.Type: GrantFiled: May 6, 1994Date of Patent: October 10, 1995Assignee: Knoll AktiengesellschaftInventors: Klaus Scheib, Peter Klein, Robert Carter
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Patent number: 5455236Abstract: The invention relates to novel cyclodextrin inclusion compounds of 5,10-methylenetetrahydrofolic acid. The surprisingly good stability of these compounds makes possible their pharmaceutical use for the first time. The invention additionally relates to a process for the preparation of the said substances and their use for the preparation of medicaments.Type: GrantFiled: July 12, 1993Date of Patent: October 3, 1995Assignee: Eprova AktiengesellschaftInventors: Hans R. Muller, Martin Ulmann, Josef Conti
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Patent number: 5446045Abstract: A series of guanine analogs having the basic structures of ##STR1## and physiological salts thereof. Also disclosed are a variety of the use of the compounds as a composition with a physiological carrier or in combination therapy with acyclovir, HBG and ganciclovir in the treatment of viral disease.Type: GrantFiled: December 20, 1993Date of Patent: August 29, 1995Inventors: Ganapathi R. Revankar, Arthur F. Lewis, Birendra K. Bhattacharya, Rodrigo V. Devivar, Robert F. Rando, Susan M. Fennewald