Abstract: The invention relates to a process for preparing highly functionalized &ggr;-butyrolactams and &ggr;-amino acids by reductive amination of mucohalic acid or its derivatives, and discloses a process for preparing pregabalin, a GABA analog with desirable medicinal activity.
Type:
Application
Filed:
February 13, 2003
Publication date:
December 4, 2003
Inventors:
Peter G. Blazecka, James Guy Davidson, Ji Zhang
Abstract: A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation.
Abstract: A method for treating circadian rhythm disorders is described. The method involves the administration of melatonin, melatonin agonists or compounds that stimulate endogenous melatonin production so that the durations of the effective plasma concentrations of melatonin, melatonin agonists or compounds that stimulate endogenous melatonin production overlap with onset or offset of pre-treatment endogenous melatonin production, to provide a circadian-rhythm phase advance or phase delay, respectively. The methods of the invention also provide for concentration and/or duration of the effective plasma concentrations of melatonin, melatonin agonists or compounds that stimulate endogenous melatonin production to be greater in the time interval between about 8 hours before the dim light endogenous melatonin onset (DLMO) to about 4 hours after DLMO than in the time interval from about 4 hours after DLMO to about 8 hours before DLMO to achieve a circadian-rhythm phase advance.
Abstract: The present invention relates to phenolic acid derivatives of the formula I and compositions for the preventing and the treating blood lipid level-related diseases comprising the phenolic acid derivatives. The compounds have excellent effects of reducing blood lipid level, inhibiting cholesterol metabolism-related enzymes and preventing and treating blood lipid level-related diseases.
Abstract: The present invention relates to novel oxime carbamyl derivatives and pharmaceutical compositions comprising said derivatives which inhibit fatty acid amide hydrolase. These pharmaceutical compositions are useful for the treatment of conditions which can be effected by inhibiting fatty acid amide hydrolase including, but not limited to, neuropathic pain, emesis, anxiety, altering feeding behaviors, movement disorders, glaucoma, brain injury, and cardiovascular disease.
Abstract: The present invention relates to novel aromatic amines of general formula (I) and to the use of these amines for the treatment of obesity, anorexia, inflammation, mental disorders an other diseases associated with the melanocortin receptors or related systems, e.g. the melanocyte stimulating hormones.
Type:
Application
Filed:
November 20, 2002
Publication date:
October 16, 2003
Inventors:
Torbjorn Lundstedt, Anna Skottner, Elisabeth Seifert, Igor Starchenkov, Peteris Trapencieris, Valerjans Kauss, Ivars Kalvins, Arne Boman
Abstract: The disclosed invention provides new polyamine analogs and derivatives containing a hydrophobic region and a polyamine region as well as methods and compositions for their use.
Abstract: Novel chiral derivitaves of non-nucleoside inhibitors (NNI), particularly R-isomers of halopyridyl and thiazoyl thiourea compounds are provided as potent inhibitors of reverse transcriptase (RT), and particularly of retroviral RT, most particularly HIV RT. The stereospecific compounds and compositions of the invention inhibit replication of retrovirus, particularly human immunodeficiency virus-1 (HIV-1) and drug resistant strains.
Type:
Application
Filed:
January 21, 2003
Publication date:
September 25, 2003
Applicant:
Parker Hughes Institute located at Roseville, Minnesota
Inventors:
Fatih M. Uckun, Taracad K. Venkatachalam
Abstract: A process is provided for preparing chirally pure S-enantiomers of &agr;-amino acids comprising the steps of: a) preparing an organometallic reagent from an alkyl halide of the formula (R)2CH(CH2)nCH2X; b) adding the organometallic reagent to carbon dioxide to afford a carboxylic acid; c) activating the carboxylic acid with an acid chloride, phosphorus trichloride, acid anhydride, or thionyl chloride in the presence of a tertiary amine base; d) reacting the product of step c) with an alkali metal salt of S-4-benzyl-2-oxazolidinone; e) treating the product of step d) with a strong non-nucleophilic base to form an enolate anion; f) trapping the enolate anion with 2,4,6-triisopropylbenzenesulfonyl azide to afford an oxazolidinone azide; g) hydrolyzing the oxazolidinone azide with an aqueous base to afford an &agr;-azido acid; h) reducing the &agr;-azido acid to the &agr;-amino acid; and i) recrystallizing the &agr;-amino acid to the chirally pure &agr;-amino acid.
Type:
Application
Filed:
November 26, 2002
Publication date:
July 31, 2003
Applicant:
Wyeth
Inventors:
Anthony Frank Kreft, Madelene Miyoko Antane, Derek Cecil Cole, Dennis Martin Kubrak, Lynn Resnick, Joseph Raymond Stock, Zheng Wang
Abstract: The present invention relates to small molecules according to the formula [I]:
which are potent inhibitors of &agr;4&bgr;1 mediated adhesion to either VCAM or CS-1 and which can be used for treating or preventing &agr;4&bgr;1 adhesion mediated conditions in a mammal such as a human.
Type:
Grant
Filed:
July 12, 2002
Date of Patent:
July 22, 2003
Assignees:
Tanabe Seiyaku Co., Ltd., Pharmacia & Upjohn Company
Inventors:
Thomas J. Lobl, Bradley R. Teegarden, Alexander Polinsky, Gilbert M. Rishton, Masafumi Yamagishi, Steven Tanis, Jed F. Fisher, Edward W. Thomas, Robert A. Chrusciel
Abstract: Disclosed are compounds of the formula:
or the pharmaceutically acceptable non-toxic salts thereof wherein;
A is N or CH;
R1 and R2 represents hydrogen or lower alkyl;
G, R3, R4, R5, R6, R7 and R8 are variables defined herein.
These compounds are modulators of CRF receptors and are therefore useful for treating affective disorders, anxiety, depression, eating disorders, and stress disorders in humans and other animals. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided.
Compounds of the invention are also useful as probes for the localization of CRF receptors and as standards in assays for CRF receptor binding. Methods of using the compounds in receptor localization studies are given.
Type:
Grant
Filed:
August 13, 2001
Date of Patent:
June 24, 2003
Assignee:
Neurogen Corporation
Inventors:
Raymond F. Horvath, Ping Ge, Taeyoung Yoon, Alan Hutchison
Abstract: There is provided a process for preparing a pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine.
Abstract: An assay is disclosed for determining whether a test compound modulates the activity of an enzyme having a metallated active site. The assay method employs a comparison of the binding ability of the metallated and unmetallated forms of the enzyme to the test compound.
Type:
Grant
Filed:
May 27, 1999
Date of Patent:
May 27, 2003
Assignee:
Hawaii Biotechnology Group, Inc.
Inventors:
Paul G. Grothaus, Dana E. Davis, Sean O'Malley
Abstract: Process for the preparation of a diasteromerically enriched phenylglycine amide derivative in which an enantomerically enriched phenylglycine amide is converted into the corresponding Schiff base with the aid of compound R2—C(O)—R3, and the Schiff base obtained is subsequently converted into the diastereomerically enriched phenyglycine amide derivative with the aid of a cyanide source, a reducing agent or an allyl organometallic compound. The phenylglycine amide derivatives obtained are interesting starting materials for the preparation of for example enantimerically enriched &agr;- and or &bgr;-amino acids and derivatives thereof, such as amides and esters, and amines.
Type:
Application
Filed:
October 9, 2002
Publication date:
May 22, 2003
Inventors:
Wilhelmus Hubertus Joseph Boesten, Harold Monro Moody, Bernardus Kaptein, Johannes Paulus Gerardus Seerden, Marcelles Van Der Sluis, Ben Lange De, Quirinus Bernardus Broxterman
Abstract: The invention relates to novel optically active polymerizable dipeptides, to the process for the preparation thereof, to the polymerization thereof and to the use of the polymers as adsorbents for the chromatographic separation of enantiomers.
Type:
Grant
Filed:
August 12, 1994
Date of Patent:
May 6, 2003
Assignee:
Bayer Aktiengesellschaft
Inventors:
Walter Lange, Michael Grosse-Bley, Bruno Bömer, Rolf Grosser, Franz-Peter Hoever
Abstract: Aromatic dehydroamino acids are disclosed that are active as LFA-1 arnagonists This activity enables these compounds to prevent inflammation which is a consequence of T cell activation and accordingly reduce or eliminate inflammatory skin disease psoriasis.
Type:
Grant
Filed:
January 5, 2001
Date of Patent:
February 4, 2003
Assignee:
Hoffman-La Roche Inc.
Inventors:
Nader Fotouhi, Paul Gillespie, Robert William Guthrie, Sherrie Lynn Pietranico-Cole, Weiya Yun
Abstract: N-heterocyclic moiety containing hydroxyethylamine compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Type:
Grant
Filed:
October 31, 2000
Date of Patent:
January 14, 2003
Assignee:
Monsanto Company
Inventors:
John J. Talley, Daniel P. Getman, Gary A. DeCrescenzo, Kathryn L. Reed, Ko-Chung Lin, John Nicholas Freskos, Michael Clare, Donald Joseph Rogier, Jr., Robert M. Heintz, Michael L. Vazquez, Richard A. Mueller
Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
Type:
Grant
Filed:
March 30, 1999
Date of Patent:
December 17, 2002
Assignees:
Athena Neurosciences, Inc., Eli Lilly & Company
Inventors:
James E. Audia, Beverly K. Folmer, Varghese John, Lee H. Latimer, Jeffrey S. Nissen, Warren J. Porter, Eugene D. Thorsett, Jing Wu
Abstract: A compound of the Formula (I):
wherein Z, R1, R, and Ar2 are as defined in the specification. This invention also relates to sulfonamide compounds of the Formula (I) that are inhibitors of procollagen C-proteinase, pharmaceutical compositions containing them, methods for their use, and methods for preparing the compounds.
Type:
Grant
Filed:
December 22, 1999
Date of Patent:
December 10, 2002
Assignee:
Syntex (U.S.A.) LLC
Inventors:
Roland Joseph Billledeau, Chris Allen Broka, Jeffrey Allen Campbell, Jian Jeffrey Chen, Sharon Marie Dankwardt, Nancy Delaet, Leslie Ann Robinson, Keith Adrian Murray Walker
Abstract: The present invention relates to small molecules according to the formula [I]:
which are potent inhibitors of &agr;4&bgr;1 mediated adhesion to either VCAM or CS-1 and which can be used for treating or preventing &agr;4&bgr;1 adhesion mediated conditions in a mammal such as a human.
Type:
Grant
Filed:
June 23, 1998
Date of Patent:
November 19, 2002
Assignees:
Tanabe Seiyaku Co., Ltd., Pharmacia & Upjohn Company
Inventors:
Thomas J. Lobl, Bradley R. Teegarden, Alexander Polinsky, Gilbert M. Rishton, Masafumi Yamagishi, Steven Tanis, Jed F. Fisher, Edward W. Thomas, Robert A. Chrusciel
Abstract: The invention relates to novel N-substituted indole-3-glyoxylamides, to processes for their preparation and to their pharmaceutical use. The compounds have antiasthmatic, antiallergic and immunosuppressant/immunomodulating actions.
Type:
Application
Filed:
January 30, 2002
Publication date:
October 31, 2002
Inventors:
Guillaume Lebaut, Cecilia Menciu, Bernhard Kutscher, Peter Emig, Stefan Szelenyi, Kay Brune
Abstract: A method for treating circadian rhythm phase disorders is described. The invention provides methods to specifically advance or delay the phase of certain circadian rhythms in humans. The disclosed methods relate to the administration of melatonin at times determined with relation to the time of dim light endogenous melatonin onset. Embodiments capable of alleviating the effects of jet lag, winter depression and shift-work sleep disturbance are provided.
Abstract: The present invention provides compounds which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease, comprising inhibiting said bone loss or excessive cartilage or matrix degradation by administering to a patient in need thereof a compound of the present invention.
Abstract: A class of novel oxime indoles is disclosed together with the use of such compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of inflammatory diseases such as septic shock.
Type:
Grant
Filed:
May 30, 2001
Date of Patent:
May 21, 2002
Assignee:
Eli Lilly and Company
Inventors:
Nicholas James Bach, Richard Waltz Harper, Michael Dean Kinnick, Ho-Shen Lin, John Michael Morin, Jr., Michael Enrico Richett
Abstract: The present application describes a process for preparing compounds of the indole type of the formula
in which A is a hydrocarbon radical which, together with the carbons to which it is attached, forms a substituted or unsubstituted mono- or polycyclic aromatic system which may contain one or more heteroatoms from the group consisting of N, O and S, and
R1, R2 independently of one another are H, a saturated, linear or branched aliphatic C1-C20-hydrocarbon radical, an unsaturated, linear or branched aliphatic C2-C20-hydrocarbon radical, a saturated or unsaturated, unsubstituted or alkyl-substituted cycloaliphatic C3-C20-hydrocarbon radical or an aromatic C5-C20-hydrocarbon radical, where these radicals may contain in their molecular skeleton one or more heteroatoms from the group consisting of the halogens, N, P, O, S, Si, Sn and B and may be substituted or unsubstituted, by cyclization of alkynylaminoaromatics of the formula
in which R1 and R2 are as defined in formula (I)
Abstract: The invention includes selected novel optically active &agr;-amino ketones which either are themselves useful or are intermediates for the preparation of known ketomethylene pseudopeptides useful as antibiotics, antibiotic enhancers, or enzyme inhibitors. Further, the present invention provides a method for dehydrogenation/asymmetrical hydrogenation to obtain essentially pure antipodes of ketomethylene pseudopeptides having two chiral centers.
Abstract: Compounds of formula (I):
or pharmaceutically acceptable salts thereof, or solvates of either entity, wherein the substituents have the values described herein, are useful as matrix metalloprotease (MMP) inhibitors
Type:
Grant
Filed:
April 11, 2000
Date of Patent:
February 26, 2002
Assignee:
Pfizer Inc
Inventors:
Michael Jonathan Fray, Roger Peter Dickinson, Kevin Neil Dack
Abstract: This invention relates to the synthesis of novel cationic, amphiphilic lipids and their application as gene transfer vehicles in vitro and in vivo. For this a series of different lipids (diglycerides, steroids) were synthesized by modification with variable cationic molecules (amino acids, biogenic amines). Compounds of this kind are, due to their capability of producing complexes with polynucleotides (DNA, RNA, Antisense oligonucleotides, ribozymes etc) suitable as vectors for gene transfer (transfection).
Abstract: Fluorinated alkyl compounds may be used as reaction intermediates or reaction products in polymerizing amino acid structures into peptides. Fluorinated methyl groups have been found to be particularly useful.
Abstract: The present invention relates to hydroxamic acid derivatives that inhibit N-Acetylated &agr;-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives to inhibit NAALADase activity, to treat a glutamate abnormality and to treat a prostate disease in an animal.
Type:
Application
Filed:
June 15, 2001
Publication date:
November 22, 2001
Inventors:
Paul F. Jackson, Kevin L. Tays, Keith M. Maclin, Barbara S. Slusher
Abstract: Compounds of formula I
wherein R1, R1-R3, R4′, R4″ and R5 are as defined in the description, have valuable pharmaceutical properties and are effective especially as NK1 and NK2 antagonists. They are prepared in a manner known per se.
Type:
Grant
Filed:
September 5, 2000
Date of Patent:
November 20, 2001
Assignee:
Novartis AG
Inventors:
Marc Gerspacher, Andreas von Sprecher, Robert Mah, Silvio Roggo, Stefan Stutz
Abstract: The subject invention pertains to novel compounds, and compositions comprising the compounds, for the treatment of cardiac arrhythmias. The subject invention further concerns a method of making the novel compounds. The novel compounds are rapidly metabolized analogs of amiodarone, having the distinct and advantageous characteristic of being metabolized to a less lipophilic compound. The new compounds can have particular utility for treating life-threatening ventricular tachyarrhythmias, especially in patients with congestive heart failure (CHF). The product can also provide effective management for ventricular arrhythmias and supraventricular arrhythmias, including atrial fibrillation and re-entrant tachyarrhythmias involving accessory pathways.
Abstract: A compound of the formula
where:
n, and
X are as defined in the specification,
and the compound possesses selectivity for inhibition of cyclooxygenase-2.
Abstract: Novel aryl derivatives comprising an aryl olefin moiety linked to a non-nucleosidic backbone moiety are disclosed. The resulting molecules are typically used as photoactivated crosslinking groups when incorporated into oligonucleotides to crosslink nucleic acid strands.
Type:
Grant
Filed:
November 10, 1998
Date of Patent:
October 16, 2001
Assignee:
Naxcor
Inventors:
Peter C. Cheng, David Albagli, Michael L. Wood
Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
Type:
Application
Filed:
March 30, 1999
Publication date:
September 6, 2001
Inventors:
JAMES E. AUDIA, BEVERLY K. FOLMER, VARGHESE JOHN, LEE H. LATIMER, JEFFREY S. NISSEN, WARREN J. PORTER, EUGENE D. THORSETT, JING WU
Abstract: Disclosed are compounds of the forumla:
or the pharmaceutically acceptable non-toxic salts thereof wherein;
A is N or CH;
R1 and R2 represents hydrogen or lower alkyl;
G, R3, R4, R5, R6, R7 and R8 are variables defined herein.
These compounds are modulators of CRF receptors and are therefore useful for treating affective disorders, anxiety, depression, eating disorders, and stress disorders in humans and other animals. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided.
Compounds of the invention are also useful as probes for the localization of CRF receptors and as standards in assays for CRF receptor binding. Methods of using the compounds in receptor localization studies are given.
Type:
Grant
Filed:
March 31, 2000
Date of Patent:
August 28, 2001
Assignee:
Neurogen Corporation
Inventors:
Raymond F. Horvath, Ping Ge, Taeyoung Yoon, Alan Hutchison
Abstract: A process for preparing 1H-indole-3-glyoxamides useful for inhibiting SPLA2 and novel intermediates useful in the preparation of such compounds.
Abstract: Compounds of formula (I),
wherein: n is 1 to 6; Het is a nitrogen containing ring fused to the benzene ring on two adjacent carbon atoms to form a bicyclic ring system which ring system may be optionally substituted; R1 is hydrogen, C1-8alkyl, C2-6alkenyl, C2-6alkyny, C3-8cycloalkyl, aryl, heteroaryl, heterocyclyl, arylC1-6alkyl, heteroarylC1-6alkyl, heterocyclylC1-6alkyl or C3-8cycloalkylC1-6alkyl; R2 is C1-6alkyl, C2-6alkenyl, arylC1-6alkyl, heteroarylC1-6alkyl or the side-chain of a naturally occurring amino acid; R3 is hydrogen, C1-6alkyl, C3-8cycloalkyl, C4-8cycloalkenyl, arylC1-6alkyl, heteroarylC1-6alkyl or heterocycylC1-6alkyl; R4 is hydrogen or C1-6alkyl; or R3 and R4 together with the nitrogen atom to which they are joined form a heterocyclic ring; wherein any group or ring, in R1-R4, is optionally substituted; and pharmaceutically acceptable salts and in vivo hydrolysable esters thereof, are described as inhibitors of the production of Tumor Necrosis Factor and/or one or more matr
Abstract: A class of novel 1H-indole-3-acetamides is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.
Type:
Grant
Filed:
October 31, 1997
Date of Patent:
June 26, 2001
Assignee:
Eli Lilly and Company
Inventors:
Nicholas J. Bach, Robert D. Dillard, Susan E. Draheim, Robert B. Hermann, Richard W. Schevitz
Abstract: A class of novel 1H-indole-3-glyoxylamides is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.
Type:
Grant
Filed:
February 26, 1999
Date of Patent:
January 16, 2001
Assignee:
Eli Lilly and Company
Inventors:
Nicholas J. Bach, Robert D. Dillard, Susan E. Draheim
Abstract: Described is a novel compound and method, useful for treatment of cardiac arrhythmias, especially useful in patients with congestive heart failure (CHF). A process for synthesizing the novel compound is also described.
Abstract: A method for treating circadian rhythm phase disorders is described. The invention provides methods to specifically advance or delay the phase of certain circadian rhythms in humans. The disclosed methods relate to the administration of melatonin at times determined with relation to the time of dim light endogenous melatonin onset. Embodiments capable of alleviating the effects of jet lag, winter depression and shiftwork sleep disturbance are provided.