Abstract: Pharmaceutical composite compositions comprising tetrahydroindolones linked to arylpiperazines and derivatives thereof are disclosed. Specifically, composite compositions useful in treating anti-psychotic disorders are disclosed. The composite compositions disclosed herein can effectively ameliorate symptoms and treat psychotic disorders without causing a decrease in cognitive function. Generally, the composite compounds consist of two moieties, moiety A and B in which a tetrahydroindolone comprises a moiety A linked through a linker L to a moiety B, where B is an arylpiperazinyl moiety. The composite compound provides anti-psychotic actively by interaction with GABA, seratoninne and dopamine receptors. The composite molecules with the combined activities will provide treat psychiatric and neurological diseases without cognitive impairment.
Type:
Grant
Filed:
July 30, 2002
Date of Patent:
August 3, 2004
Assignee:
Spectrum Pharmaceuticals, Inc.
Inventors:
David B. Fick, Mark M. Foreman, Alvin J. Glasky, David R. Helton
Abstract: A novel process for the asymmetric synthesis of an amino-pyrrolidinone of the type shown below from appropriate pyrrolidinones is described.
These compounds are useful as intermediates for MMP and TACE inhibitors.
Type:
Grant
Filed:
March 14, 2003
Date of Patent:
August 3, 2004
Assignee:
Bristol-Myers Squibb Company
Inventors:
Nicholas A. Magnus, Pasquale N. Confalone, Scott A. Savage, Matthew Yates, Robert E. Waltermir, David J. Meloni, Silvio Campagna
Abstract: The present invention provides analogues of autoinducer molecules that are derivatized to allow their attachment to other molecules and surfaces. Libraries of the autoinducer analogues are also contemplated. Also provided are methods for using the compounds of the invention to produce compositions, such as immunoconjugates, antibodies and vaccines, which are useful for treating and preventing disease states in a subject. The compositions of the invention are also useful in various assays, including assessing the autoinducer load in a subject.
Abstract: A tetrahydroindolone derivative or analogue comprises a 9-atom bicyclic moiety, moiety A, linked through a linker L to a moiety B, where B is a carboxylic acid, a carboxylic acid ester, or a moiety of the structure N(Y1)-D, where Y1 can be one of a variety of substituents, including hydrogen or alkyl, and D is a moiety that enhances the pharmacological effects, promotes absorption or blood-brain barrier penetration of the derivative or analogue. The moiety A has a six-membered ring fused to a five-membered ring. The moiety A can have one, two, or three nitrogen atoms in the five membered ring. The moiety A can be a tetrahydroindolone moiety. The moiety B can be one of a variety of moieties, including moieties having nootropic activity or other biological or physiological activity.
Type:
Grant
Filed:
April 20, 2001
Date of Patent:
July 6, 2004
Assignee:
Spectrum Pharmaceuticals, Inc.
Inventors:
David B. Fick, Mark M. Foreman, Alvin J. Glasky
Abstract: Compounds of general formula (I): wherein R1, R2, Y, (X)o, (W)n, (V)m, Z and U are as defined in the specification, are inhibitors of cruzipain and other cysteine protease inhibitors and are useful as therapeutic agents, for example in Chagas' disease, or for validating therapeutic target compounds.
Abstract: The present invention provides a method of treating ocular hypertension or glaucoma which comprises administering to an animal having ocular hypertension or glaucoma therapeutically effective amount of a compound represented by the general formula I;
wherein X, Y, Z, D and R3 are as defined in the specification.
Type:
Grant
Filed:
June 2, 2003
Date of Patent:
May 11, 2004
Assignee:
Allergan, Inc.
Inventors:
David W. Old, Thang D. Dinh, Robert M. Burk
Abstract: Novel quaternary amidino-containing compounds of the general formulae (I), (II), (III), (IV), (V) and (VI): including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and the compositions are useful in vitro or in vivo for preventing or treating conditions in mammals characterized by undesired thrombosis.
Type:
Application
Filed:
October 16, 2003
Publication date:
April 22, 2004
Inventors:
Bing-Yan Zhu, Wenrong Huang, Penglie Zhang, Zhaozhong Jon Jia, Liang Bao, Yanhong Wu, Robert M. Scarborough
Abstract: The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.
Type:
Grant
Filed:
March 8, 2002
Date of Patent:
April 13, 2004
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Roger D. Tung, Mark A. Murcko, Govinda Rao Bhisetti
Abstract: The invention concerns 2-oxo-1-pyrrolidine derivatives and a process for preparing them and their uses. The invention also concerns a process for preparing &agr;-ethyl-2-oxo-1-pyrrolidine acetamide derivatives from unsaturated 2-oxo-1-pyrrolidine derivatives. Particularly the invention concerns novel intermediates and their use in methods for the preparation of S-&agr;-ethyl-2-oxo-1-pyrrolidine acetamide.
Type:
Grant
Filed:
August 20, 2002
Date of Patent:
March 30, 2004
Assignee:
UCB Farchim S.A.
Inventors:
John Surtees, Violeta Marmon, Edmond Differding, Vincent Zimmermann
Abstract: The present patent application relates to 3-(2,5-diaminophenyl)acrylamide derivatives of general formula (I) or to physiologically tolerated, water-soluble-salts thereof
and to agents containing said compounds and used for oxidative dyeing of fibers.
Abstract: The present invention relates to highly enantiomerically pure lactam-substituted propanoic acid derivatives and methods of making and using therefor. The invention involves a multi-step synthesis to produce the lactam compounds. In one step of the reaction sequence, asymmetric hydrogenation of a lactam-enamide was performed to produce an intermediate that can ultimately be converted to a series of pharmaceutical compounds. The invention also contemplates the in situ synthesis of an intermediate of the multi-step synthesis, which provides economic advantages to the overall synthesis of the lactam compounds.
Type:
Grant
Filed:
September 20, 2001
Date of Patent:
February 3, 2004
Assignee:
Eastman Chemical Company
Inventors:
Neil Warren Boaz, Sheryl Davis Debenham
Abstract: This invention is directed to aromatic sulfone hydroxamates (also known as “aromatic sulfone hydroxamic acids”) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.
Type:
Application
Filed:
May 10, 2002
Publication date:
January 15, 2004
Inventors:
John N. Freskos, Yvette M. Fobian, Thomas E. Barta, Daniel P. Becker, Louis J. Bedell, Terri L. Boehm, Jeffery N. Carroll, Gary A. DeCrescenzo, Susan L. Hockerman, Darren J. Kassab, Steve A. Kolodziej, Joseph McDonald, Deborah A. Mischke, Monica B. Norton, Joseph G. Rico, John J. Talley, Clara I. Villamil, Lijuan Jane Wang
Abstract: The present invention provides an NF-kappa B activation inhibitor, an inflammatory cytokine production inhibitor, a matrix metalloprotease production inhibitor, an inflammatory cell adhesion factor expression inhibitor, and an anti-inflammatory agent, an antirheumatic agent, an immuno-suppressive agent, an antiallergic agent, an antiviral agent, or a therapeutic agent for arteriosclerosis, which comprise, as the active ingredient, a cyclopropanecarboxylic acid amide compound or a pharmaceutically acceptable salt thereof effective for the treatment of inflammatory diseases.
Abstract: Picornaviral 3C protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions that contain these compounds, are suitable for treating patients or hosts infected with one or more picornaviruses.
Type:
Grant
Filed:
September 7, 2001
Date of Patent:
November 18, 2003
Inventors:
Peter S. Dragovich, Thomas J. Prins, Ru Zhou
Abstract: A substituted 1,5-dihydropyrrol-2-one compound of formula I:
and methods for preparing the compounds. Also disclosed are pharmarceutical compositions comprising the compounds and methods of using the compounds for the treatment or prophylaxis of pain, inflammatory and allergic reactions, depressions, drug abuse and various other diseases or conditions.
Type:
Grant
Filed:
February 6, 2002
Date of Patent:
November 4, 2003
Assignee:
Gruenenthal GmbH
Inventors:
Michael Przewosny, Hans-Dietrich Stachel, Hermann Poschen-Rieder
Abstract: Compounds of the formula:
where the formula variables are as defined in the disclosure, advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as RVP. Intermediates and synthetic methods for preparing such compounds are also described.
Type:
Grant
Filed:
April 12, 2001
Date of Patent:
August 26, 2003
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Theodore O. Johnson Jr., Ye Hua, Hiep T. Luu, Peter S. Dragovich
Abstract: This invention relates to novel lactams having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A&bgr;-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to &bgr;-amyloid production such as Alzheimer's disease and Down's Syndrome.
Type:
Application
Filed:
November 1, 2002
Publication date:
July 17, 2003
Inventors:
Richard E. Olson, Thomas P. Maduskuie, Lorin Andrew Thompson
Abstract: The present invention is directed to non-peptidic factor Xa inhibitors which are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases.
Type:
Application
Filed:
September 16, 2002
Publication date:
June 12, 2003
Applicant:
3-Dimensional Pharmaceuticals, Inc.
Inventors:
Scott C. Miller, Juan Jose Marugan Sanchez, Kristin D. Haslow, Jonathan Hall
Abstract: Carbamate compounds of 2-heteroaryl-1,2-ethanediol are described. The compounds are effective in the treatment of disorders of the central nervous system, especially as anti-convulsive or anti-epileptic agents.
Abstract: The present invention relates to cyclized amide derivatives of formula (I)
These cyclized amide derivatives are useful for treating or preventing neuronal damage associated with neurological diseases. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage.
Type:
Grant
Filed:
January 3, 2002
Date of Patent:
April 22, 2003
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
David Lauffer, Michael Mullican, Brian Ledford
Abstract: This invention is directed to methods of synthesizing densely functionalized pyrrolidine compounds through the use of intramolecular Diels Alder reactions.
Type:
Grant
Filed:
March 12, 2002
Date of Patent:
January 28, 2003
Assignee:
Ortho McNeil Pharmaceutical, Inc.
Inventors:
Pranab Mishra, Sengen Sun, William V. Murray
Abstract: Autoinducer compounds which enhance gene expression in a wide variety of microorganisms, therapeutic compositions and therapeutic methods wherein gene expression within microorganisms is regulated are disclosed.
Abstract: The invention relates to 1,5-dihydropyrrol-2-ones of Formula 1 which contain an aryl radical in the 1-position and a secondary amine radical in the 4-position, to a process for making and for a process to treat various forms of epilepsies and of states of anxiety and tension.
Type:
Grant
Filed:
August 31, 2000
Date of Patent:
December 31, 2002
Assignee:
Arzneimittelwerk Dresden GmbH
Inventors:
Thomas Arnold, Klaus Unverferth, Hans-Joachim Lankau, Angelika Rostock, Christine Tober, Chris Rundfeldt, Reni Bartsch
Abstract: Objects of the present invention are to create compounds having urea structure as basic structure and having a sulfur atom and an amide bond in side chains and to find pharmacological effects thereof, particularly TNF-&agr; production inhibitory effects.
Abstract: A compound of the formula:
is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
Type:
Grant
Filed:
April 18, 2001
Date of Patent:
October 29, 2002
Assignee:
Abbott Laboratories
Inventors:
Hing Leung Sham, Daniel W. Norbeck, Xiaoqi Chen, David A. Betebenner, Dale J. Kempf, Thomas R. Herrin, Gondi N. Kumar, Stephen L. Condon, Arthur J. Cooper, Daniel A. Dickman, Steven M. Hannick, Lawrence Kolaczkowski, Patricia A. Oliver, Daniel J. Plata, Peter J. Stengel, Eric J. Stoner, Jieh-Heh J. Tien, Jih-Hua Liu, Ketan M. Patel
Abstract: The present invention relates to lactam derivatives of the formula
wherein R1, R2, R3, A, X, Z, n and the dashed line are defined herein, and pharmaceutical compositions thereof, to processes and intermediates for their preparation, and to their medicinal use as selective agonists and antagonists of serotonin 1 (5-HT1) receptors, specifically, of one or both of the 5-HT1A and 5-HT1D receptors. These compounds are useful in treating or preventing migraine, depression and other disorders for which a 5-HT1 agonist or antagonist is indicated.
Abstract: Compounds of the formula I
in which R1, R2 and R3 have the stated meanings, and their physiologically acceptable salts, inhibit the binding of fibrinogen to the corresponding receptor and can be used for the treatment of thromboses, osteoporoses, oncoses, stroke, myocardial infarct, ischemias, inflammations, arteriosclerosis and osteolytic disorders.
Type:
Grant
Filed:
May 3, 1996
Date of Patent:
September 24, 2002
Assignee:
Merck Patent Gesellschaft mit beschraenkter Haftung
Inventors:
Joachim Gante, Hörst Juraszyk, Peter Raddatz, Hanns Wurziger, Sabine Bernotat-Danielowski, Guido Melzer
Abstract: The current invention discloses useful pharmaceutical compositions containing amidino derivative useful as nitric oxide synthase inhibitors.
Type:
Grant
Filed:
July 28, 1998
Date of Patent:
September 10, 2002
Assignee:
G.D. Searle & Co.
Inventors:
Donald W. Hansen, Jr., Mark G. Currie, E. Ann Hallinan, Kam F. Fok, Timothy J. Hagen, Arija A. Bergmanis, Steven W. Kramer, Len F. Lee, Suzanne Metz, William M. Moore, Karen B. Peterson, Barnett S. Pitzele, Dale P. Spangler, R. Keith Webber, Mihaly V. Toth, Mahima Trivedi, Foe S. Tjoeng
Abstract: Compounds represented by general formula (1) or salts thereof which have a matrix metalloprotease inhibitory activity and are useful as drugs, wherein the rings A and B represent each an optionally substituted homocycle or heterocycle, etc.; R1s are the same or different and each represents hydrogen, optionally substituted hydrocarbyl, acyl, etc.; X1 represents a bond, optionally substituted divalent aliphatic hydrocarbyl, etc.; X2 represents a bond, optionally substituted divalent aliphatic hydrocarbyl, —O—, etc.; Ys are the same or different represents hydrogen, optionally substituted hydrocarbyl, oxo, etc.; m is 0 or 1; n is an integer of 1 to 3; q1 is an integer of 1 to 2n+4; and q2 is an integer of 0 to 2n+3, provided that q1+q2 is 2n+4.
Type:
Grant
Filed:
March 20, 2001
Date of Patent:
July 16, 2002
Assignee:
Takeda Chemical Industries, Ltd.
Inventors:
Toshiro Yamashita, Hiroshi Nara, Masayuki Takizawa, Koji Yoshimura
Abstract: The present invention relates to compounds of the formula
wherein R1, R2, R3, X, Y and the dashed line are defined as in the specification, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. These compounds are useful as psychotherapeutic agents.
Inventors:
Theodore O. Johnson, Jr., Shao Song Chu, Brian Walter Eastman, Ye Hua, Hiep The Luu, Siegfried Heinz Reich, Donald James Skalitzky, Yi Yang, Thomas F. Hendrickson, Fora P. Chan
Abstract: The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.
Type:
Grant
Filed:
September 30, 1999
Date of Patent:
May 21, 2002
Assignee:
Vertex Pharmaceuticals, Inc.
Inventors:
Roger D. Tung, Mark A. Murcko, Govinda Rao Bhisetti
Abstract: This invention is directed to methods of treating conditions which present with low bone mass, particularly osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth comprising administering prostaglandin agonists which are EP4 receptor selective prostaglandin agonists.
Type:
Application
Filed:
November 16, 2001
Publication date:
April 4, 2002
Inventors:
Kimberly O. Cameron, HuaZhu Ke, Bruce A. Lefker, David D. Thompson
Abstract: Enamine derivatives of formula (1) are described: 1
Type:
Application
Filed:
April 16, 2001
Publication date:
March 28, 2002
Inventors:
Timothy John Norman, John Robert Porter, Brian Woodside Hutchinson, Andrew James Ratcliffe, John Clifford Head, Rikki Peter Alexander, Barry John Langham, Graham John Warrellow, Sarah Catherine Archibald, Janeen Marsha Linsley
Abstract: Efficient synthetic routes for the preparation of rhinovirus protease inhibitors of formula I, as well as key intermediates useful in those synthetic routes.
Type:
Grant
Filed:
August 23, 2000
Date of Patent:
March 12, 2002
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Qingping Tian, Naresh K. Nayyar, Srinivasan Babu, Junhua Tao, Terence Jarold Moran, Raymond Dagnino, Jr., Lennert J. Mitchell, Jr., Travis Paul Remarchuk, Michael Joseph Melnick, Steven Lee Bender
Abstract: The invention relates to a novel process for the alternative preparation of N-methyl-N-[(1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidin-1-yl)ethyl]-2,2-diphenylacetamide or N-methyl-N-[(1R)-1-phenyl-2-((3R)-3-hydroxypyrrolidin-1-yl)ethyl]-2,2-diphenylacetamide, and the novel compounds N-methyl-N-[(1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidin-1-yl)ethane] and N-methyl-N[(1R)-1-phenyl-2-((3R)-3-hydroxypyrrolidin-1-yl) ethane], which are prepared as intermediates.
Type:
Grant
Filed:
January 26, 2001
Date of Patent:
February 5, 2002
Assignee:
Merck Patent GmbH
Inventors:
Andreas Bathe, Bernd Helfert, Karl-August Ackermann, Rudolf Gottschlich, Ingeborg Stein, Jens Budak
Abstract: Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
Type:
Grant
Filed:
November 7, 1997
Date of Patent:
January 29, 2002
Assignee:
Texas Biotechnology Corp.
Inventors:
Ming Fai Chan, Chengde Wu, Bore Gowda Raju, Timothy Kogan, Erik Joel Verner, Rosario Silvestre Castillo, Venkatachalapathi Yalamoori, Adam Kois, Vitukudi Narayanaiyengar Balaji