Abstract: Compositions of matter and methods for enhancing bioassay performance are disclosed. More particularly, the composition of matter comprises a molecularly compact polymer-ligand conjugate capable of self-orienting on a surface to improve the orientation of the ligand/receptor binding domains within the bioassay at the nanoscopic level. In a preferred embodiment, the molecularly compact polymer comprises a dendrimer polymer such as a fifth generation polyamidoamine dendrimer having exterior surface hydroxyl and amine functional groups, and the ligand/receptor comprises an antibody or Fab.
Type:
Grant
Filed:
August 27, 2001
Date of Patent:
August 10, 2004
Assignee:
The United States of America as represented by the Secretary
of the Army
Inventors:
Ray Yin, H. Dupont Durst, Peter A. Emanuel, Gary L. Hagnauer
Abstract: Universal supports for oligonucleotide synthesis include a support material represented by the following formula:
In this formula, substituent A is selected from H, alkyl, aryl, or a polymeric or silica base material; substituent B is selected from acyl, aroyl, or a polymeric or silica base material; and substituent C is selected from a dimethoxytrityl group or a protecting group removable under acidic or neutral conditions. For the supports, one of substituents A or B constitutes the polymeric or silica base material. In use, an oligonucleotide is attached to the support at substituent C.
Abstract: The present invention relates to a novel class of androgen receptor targeting agents (ARTA), which contain a haloacetamide or azide moiety and are alkylating agents.
Abstract: The novel benzamide derivative represented by formula (1) and the novel anilide derivative represented by formula (13) of this invention has differentiation-inducing effect, and are, therefore, useful a therapeutic or improving agent for malignant tumors, autoimmune diseases, dermatologic diseases and parasitism. In particular, they are highly effective as an anticancer drug, specifically to a hematologic malignancy and a solid carcinoma.
Abstract: The present invention relates to novel thyroid receptor ligands and, more particularly, relates to malonamic acids and derivatives thereof of Formula I, which are useful in the treatment of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorders, thyroid disease, hypothyroidism, thyroid cancer and related disorders and diseases such as diabetes mellitus, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss. The present invention also provides methods, pharmaceutical compositions and kits for treating such diseases and disorders.
Type:
Application
Filed:
October 10, 2003
Publication date:
April 22, 2004
Inventors:
Yuan-Ching P. Chiang, Gary E. Aspnes, Kimberly G. Estep
Abstract: The present invention provides novel compounds possessing antibacterial, antifungal, antiviral, anticancer, and/or antiparasitic activities. Pharmaceutical compositions containing these compounds, methods of making and methods for using these compounds are also provided.
Type:
Application
Filed:
September 18, 2003
Publication date:
April 1, 2004
Inventors:
Janos Botyanszki, Dong-Fang Shi, Christopher Don Roberts, Mikail Hakan Gezginci, Stephen Corey Valdez, Sherwin Sattarzadeh
Abstract: The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.
Type:
Grant
Filed:
December 5, 2001
Date of Patent:
March 30, 2004
Inventors:
Prabha N. Ibrahim, Robert Jiang, Christopher Morrison, Kevin Shenk, Jeff A. Zablocki, Richard Lawn
Abstract: Compounds of Formula I and Formula II, and their N-oxides and agriculturally suitable salts, are disclosed that are useful for controlling invertebrate pests, Formula (I), Formula (II) wherein A, B, J, R1, R2, R3, R4, and n are as defined in the disclosure. Also disclosed are compositions comprising the compounds of Formula I or Formula II and methods for controlling invertebrate pests that involve contacting the invertebrate pests or their environment with an effective amount of a compound of Formula (I) or Formula (II).
Abstract: The present invention provides an AP-1 activation inhibitor, NF-kappa B activation inhibitor, inflammatory cytokine production inhibitor, matrix metalloprotease production inhibitor, inflammatory cell adhesion molecule expression inhibitor, anti-inflammatory agent, antirheumatic agent, immunosuppressant, cancer metastasis inhibitor, remedy for arteriosclerosis and antiviral agent which contain the benzene derivative of the following general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.
Abstract: A solid phase synthetic method for preparing arylretinamides is provided. The method comprises reacting hexachloroacetone with a solvent-suspended resin-bound triphenylphosphine to provide a suspension comprising an activated chlorinating reagent; reacting retinoic acid with the activated chlorinating reagent to provide retinoyl chloride; adding pyridine and a select arylamine to the resulting mixture; and stirring the resulting mixture for a time and at a temperature sufficient for the select arylamine to react with the retinoyl chloride and provide the arylretinamide. Also provided, are select arylretinamides that can be prepared by the present method, and methods of using such arylretinamides to induce apoptosis in cancer cells.
Type:
Grant
Filed:
July 8, 2002
Date of Patent:
February 24, 2004
Assignee:
The Ohio State University Research Foundation
Inventors:
Robert W. Curley, Jr., Serena M. Mershon
Abstract: Acylated &agr;-hydroxyarylbutanamines and related sulfonamides, ureas and carbamates that inhibit aspartyl protease are disclosed, as are methods of treating diseases, particularly HIV, using these compounds.
Type:
Grant
Filed:
October 22, 2001
Date of Patent:
February 24, 2004
Assignee:
Enanta Pharmaceuticals, Inc.
Inventors:
Yat Sun Or, Guoqiang Wang, John Rougas, Jude Elizabeth Mathews, Kate Ryan Muldoon, Vincent Alfred Boyd, Jens Werner Eckstein, Steven Wayne Riesinger
Abstract: Amino acid derivative as carrier compounds and compositions which are useful in the delivery of active agents are provided. The active agents can be a peptide, mucopolysaccharide, carbohydrate, or lipid. Methods of administration, including oral administration, and preparation are provided as well.
Type:
Grant
Filed:
July 15, 2002
Date of Patent:
February 17, 2004
Assignee:
Emisphere Technologies, Inc.
Inventors:
David Gscheidner, Andrea Leone-Bay, Eric Wang, John J. Freeman, Doris C. O'Toole, Lynn Shields
Abstract: Compounds of the formula
in which W is O, S, S(O) or S(O)2; X is —SR4, —S(O)R4, or —S(O)2R4, —S(O)2NR5R6; or X is —C(O)NR5R6 provided that —C(O)NR5R6 is located at the 3′, 4′ or 5′ position; Y is O or H2; Z is hydrogen, halogen, hydroxy, optionally substituted alkoxy, aralkoxy, acyloxy or alkoxycarbonyloxy; R is hydrogen, halogen, trifluoromethyl, lower alkyl or cycloalkyl; R1 is hydroxy, optionally substituted alkoxy, aryloxy, heteroaryloxy, aralkyloxy, cycloalkoxy, heteroaralkoxy or —NR5R6; R2 is hydrogen, halogen or alkyl; R3 is halogen or alkyl; R4 is optionally substituted alkyl, aryl, aralkyl, heteroaralkyl or heteroaryl; R5, R6 and R7 are independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; or R5 and R6 combined are alkylene optionally interrupted by O, S, S(O), S(O)2 or NR7 which together with the nitrogen atom to which they are attached form a 5- to 7-membered ring;
Abstract: The invention relates to methods of synthesizing libraries of diverse and complex highly substituted 2,4-dioxopiperidine compounds of the general formula:
wherein R1, R2 and R3 are as herein described, novel intermediates useful for synthesizing such 2,4-dioxopiperidine compounds and methods for identifying and isolating the compounds.
Abstract: Compounds of the formula I,
in which R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(8), R(30) and R(31) have the meanings indicated in the claims, are very particularly suitable as novel and antiarrythmic active compounds, in particular for the treatment and prophylaxis of atrial arrythmias, e.g. atrial fibrillation (AF), or atrial flutter.
Type:
Grant
Filed:
September 24, 2002
Date of Patent:
February 3, 2004
Assignee:
Aventis Pharma Deutschland GmbH
Inventors:
Joachim Brendel, Wolfgang Schmidt, Peter Below
Abstract: The present invention relates to a synthetic process for the preparation of a novel class of androgen receptor targeting agents (ARTA) which demonstrate androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor.
Type:
Application
Filed:
October 22, 2002
Publication date:
January 22, 2004
Inventors:
James T. Dalton, Duane D. Miller, Yali He, Donghua Yin
Abstract: This application relates to a compound of formula I (or a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.
Type:
Grant
Filed:
April 25, 2002
Date of Patent:
January 13, 2004
Assignee:
Eli Lilly and Company
Inventors:
Douglas Wade Beight, Trelia Joyce Craft, Jeffry Bernard Franciskovich, Theodore Goodson, Jr., Steven Edward Hall, David Kent Herron, Valentine Joseph Klimkowski, John Joseph Masters, David Mendel, Guy Milot, Jason Scott Sawyer, Robert Theodore Shuman, Gerald Floyd Smith, Anne Louise Tebbe, Jennifer Marie Tinsley, Leonard Crayton Weir, James Howard Wikel, Michael Robert Wiley, Ying Kwong Yee
Abstract: The present invention relates N-substituted glycine derivatives 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:
January 13, 2004
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
David Lauffer, Brian Ledford, Michael Mullican
Abstract: This invention is directed to a class of compounds (Formula I) including hydroxyalkanoyl amino pyrazoles, hydroxyalkanoyl amino thiadiazoles, hydroxyalkanoyl amino acid esters, hydroxyalkanoyl amino acid amides, hydroxyalkanoyl amino alcohols, hydroxyalkanoyl amino ketoes, hydroxyalkanoyl amino hydantoins, hydroxyalkanoyl anilines, and hydroxyalkanoyl derivatives of privileged structures. The invention is also directed to a pharmaceutical formation comprising such compound in a pharmaceutically acceptable salt form or prodrug thereof. The invention is further directed to a method for inhibiting &bgr;-amyloid peptide release and/or synthesis, a method for inhibiting &ggr;-secretase activity and a method for treating neurological disorders associated with &bgr;-amyloid peptide production. The method comprises administering to a host a pharmaceutical formulation comprising an effective amount of a compound of Formula I. The compounds of Formula I are useful in the prevention and treatment of Alzheimer's disease.
Type:
Application
Filed:
January 31, 2003
Publication date:
January 8, 2004
Inventors:
Jay S. Tung, Ashley C. Guinn, Gene Thorsett, Mike A. Pleiss
Abstract: Phenoxyethylamine derivatives of general formula (I) having high affinity for the 5-HT1A receptor, methods for preparing same, pharmaceutical compositions containing said derivatives, and their use, in particular as gastric acid secretion inhibitors or as antiemetics, are disclosed. In general formula (I), Ar is phenyl substituted by one or more substituents; and R is a C1-10 hydrocarbon radical selected from straight or branched alkyl, alkenyl or alkynyl radicals, saturated or unsaturated mono- or polycyclic cycloalkyl, cycloalkylalkyl or alkylcycloalkyl radicals; a pyridyl or isoquinolyl radical, phenyl optionally substituted by one or more substituents, and salts thereof.
Type:
Grant
Filed:
April 8, 2002
Date of Patent:
December 30, 2003
Assignee:
Societe de Conseils de Recherches et D'Applications
Scientifiques (S.C.R.A.S.)
Inventors:
Dennis Bigg, Jacques Pommier, Christiane Martin, Pierre Roubert, Jean Pierre Defaux
Abstract: The present invention relates to oxygenated esters of 4-substituted-phenylamino benzhydroxamic acid derivatives, pharmaceutical compositions, and methods of use thereof.
Type:
Application
Filed:
January 23, 2003
Publication date:
December 18, 2003
Inventors:
Stephen Douglas Barrett, Michael David Kaufman, Gordon William Rewcastle, Julie Ann Spicer
Abstract: The present invention relates to thiourea compounds and the pharmaceutical compositions containing the same, and particularly, to novel thiourea compounds as an antagonist against vanilloid receptor (VR) and the pharmaceutical compositions thereof. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides a pharmaceutical composition for prevention or treatment of these diseases.
Type:
Application
Filed:
February 20, 2003
Publication date:
November 13, 2003
Inventors:
Young Ger Suh, Uh Taek Oh, Hee Doo Kim, Jee Woo Lee, Hyeung Geun Park, Young Ho Park, Jung Bum Yi
Abstract: Compounds of formula I,
in which R1, R2, A, and B having the definitions set forth in the claims, are valuable pharmacologically active compounds, which exhibit a strong antithrombotic effect and are suitable, for example, for treating thromboembolic diseases and restenoses. They are reversible inhibitors of the blood clotting enzyme factor VIIa and can in general be applied in conditions in which an undesired activity of factor VIIa is present or for the cure or prevention of which an inhibition of factor VIIa is intended. Also disclosed are processes for the preparation of compounds of formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.
Type:
Grant
Filed:
October 1, 2001
Date of Patent:
November 11, 2003
Assignee:
Aventis Pharma Deutschland GmbH
Inventors:
Manfred Schudok, Otmar Klingler, Hans-Peter Nestler, Hans Matter, Herman Schreuder
Abstract: The present invention is directed to selective LXR modulators, small molecule compounds corresponding to Formula I and is further directed to a process of treating a condition in a mammal that is modulated by LXR using a therapeutically effective dose of a compound of Formula I.
Type:
Application
Filed:
December 23, 2002
Publication date:
November 6, 2003
Applicant:
Pharmacia Corporation
Inventors:
Nizal S. Chandrakumar, Christopher R. Dalton, James W. Malecha, Michael B. Tollefson, Jennifer Ann Van Camp, Philip B. Cox
Abstract: A substrate for solid phase synthesis comprising a solid phase-linker combination of the formula I is disclosed. Also disclosed are processes for preparing the substrate and chemical intermediates useful therein. Among the novel intermediates are compounds of the formula II wherein R1 is —NO2 or —CHO; R2 is —OCH3, —CHO or —H; R3 is chosen from the group consisting of hydroxyl, the residue of a solid support having a plurality of amino groups, and the residue of an ester, and n=1 or 3-12.
A substrate of solid phase synthesis of the formula III is also disclosed.
Abstract: Novel biphenyl derivatives of the general formula (I), in which Y, R R1, R2, R3, R4, m, o and p are as defined in claim 1, and their physiologically acceptable salts and solvates are integrin inhibitors and can be employed for combating thrombosis, cardiac infarction, coronary heart disease, arteriosclerosis, inflammation, tumours, osteoporosis, infections aid restenosis after angioplasty or in pathological processes which are maintained or propagated by angiogenesis.
Abstract: A group of benzamide compounds are disclosed which are useful for treating neurodegenerative disorders. Methods for making these compounds are provided. These materials are formed into pharmaceutical compositions for oral or intravenous administration to patients suffering from conditions such as Parkinson's disease which can exhibit themselves as progressive loss of central nervous system function. The compounds can arrest or slow the progressive loss of function.
Type:
Application
Filed:
December 12, 2002
Publication date:
September 18, 2003
Inventors:
William Flitter, William Garland, Richard Paylor, Allan Wilcox
Abstract: Compounds of the formula
where the variables have the meaning defined in the specification, which bind specifically or selectively to to RAR&agr; retinoid receptors.
Type:
Grant
Filed:
September 19, 2002
Date of Patent:
September 16, 2003
Assignee:
Allergan, Inc.
Inventors:
Tien T. Duong, Richard Beard, Roshantha A. Chandraratna
Abstract: The invention relates to derivatives of amidino-benzylamine, especially derivatives of 4-amidino-benzylamine, with two bonded amino acids. These derivatives represent a novel group of highly active and very selective F Xa-inhibitors for treating cardiovascular diseases and thrombotic events.
Type:
Application
Filed:
March 21, 2003
Publication date:
September 4, 2003
Inventors:
Jorg Sturzebecher, Torsten Steinmetzer, Sebastian Kunzel, Andreas Schweinitz
Abstract: The invention concerns the use of amide derivatives of formula (I) wherein: R1 and R2 are substituents such as hydroxy, C1-6alkoxy, mercapto, C1-6alkylthio, amino, C1-6alkylamino and di-(C1-6alkyl)amino; m and p are independently 0-3; R3 is C1-4alkyl; q is 0-4; and R4 is aryl or cycloalkyl; or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in the treatment of diseases or medical conditions mediated by cytokines.
Type:
Application
Filed:
October 8, 2002
Publication date:
September 4, 2003
Applicant:
ZENECA LIMITED
Inventors:
Dearg S. Brown, George R. Brown, Philip Cohen
Abstract: This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, &bgr;-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.
Type:
Grant
Filed:
March 5, 2001
Date of Patent:
September 2, 2003
Assignee:
TransTech Pharma, Inc.
Inventors:
Adnan M. M. Mjalli, Ramesh Gopalaswamy, Kwasi S. Avor, Christopher L. Wysong, Andrew Patron
Abstract: The present invention refers to synthetic protease inhibitors having an axis of symmetry C2 or pseudo-C2 characterised by possessing, in the central portion: (1) preferably, a dihydroxyethylene function, which is isosteric with a peptidic bond; (2) a peptidemimetic bridge between the two nitrogens of the main chain and (3) radicals capable of mimetising amino acids. These new protease inhibitors are a base for the preparation of anti-viral formulations capable of inhibiting HIV virus proliferation.
Type:
Application
Filed:
November 15, 2002
Publication date:
August 21, 2003
Inventors:
Emerson Poley Pecanha, Luciana J.O. Figueiredo, Vera Bongertz, Octavio Augusto Ceva Antunes, Amilcar Tanuri, Rodrigo de Moraes Brindeiro
Abstract: This application relates to a compound of formula I (or a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.
Type:
Grant
Filed:
September 21, 2001
Date of Patent:
August 12, 2003
Assignee:
Eli Lilly and Company
Inventors:
Douglas Wade Beight, Trelia Joyce Craft, Jeffry Bernard Franciskovich, Theodore Goodson Jr., Steven Edward Hall, David Kent Herron, Valentine Joseph Klimkowski, Jeffrey Alan Kyle, John Joseph Masters, David Mendel, Guy Milot, Jason Scott Sawyer, Robert Theodore Shuman, Gerald Floyd Smith, Anne Louise Tebbe, Jennifer Marie Tinsley, Leonard Crayton Weir, James Howard Wikel, Michael Robert Wiley, Ying Kwong Yee
Abstract: The present invention discloses compounds, which are novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.
Type:
Application
Filed:
October 23, 2002
Publication date:
July 31, 2003
Applicant:
Schering Corporation
Inventors:
Anandan Palani, Sherry A. Shapiro, Mark D. McBriar, Jing Su
Abstract: Compounds of the formula
in which W is O, S, S(O) or S(O)2; X is —SR4, —S(O)R4, or —S(O)2R4, —S(O)2NR5R6; or X is —C(O)NR5R6 provided that —C(O)NR5R6 is located at the 3′, 4′ or 5′ position; Y is O or H2; Z is hydrogen, halogen, hydroxy, optionally substituted alkoxy, aralkoxy, acyloxy or alkoxycarbonyloxy; R is hydrogen, halogen, trifluoromethyl, lower alkyl or cycloalkyl; R1 is hydroxy, optionally substituted alkoxy, aryloxy, heteroaryloxy, aralkyloxy, cycloalkoxy, heteroaralkoxy or —NR5R6; R2 is hydrogen, halogen or alkyl; R3 is halogen or alkyl; R4 is optionally substituted alkyl, aryl, aralkyl, heteroaralkyl or heteroaryl; R5, R6 and R7 are independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; or R5 and R6 combined are alkylene optionally interrupted by O, S, S(O), S(O)2 or NR7 which together with the nitrogen atom to which they are attached form a 5- to 7-membered ring;
Abstract: The present invention provides the compound having the structure:
wherein each of R1 and R2 are independently the same as or different from each other; when R1 and R2 are the same, each is a substituted or unsubstituted arylamino, cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiozoleamino group; when R1 and R2 are different, R1=R3—N—R4, wherein each of R3 and R4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R3 and R4 bond together to form a piperidine group and R2 is a hydroxylamino, hydroxyl, amino, alkylamino, dialkylamino or alkyloxy group; and n is an integer from about 4 to about 8.
The present invention also provides a method of selectively inducing terminal differentiation of neoplastic cells and thereby inhibiting proliferation of such cells.
Type:
Grant
Filed:
November 2, 2001
Date of Patent:
April 20, 2004
Assignees:
Sloan-Kettering Institute for Cancer Research, The Trustees of Columbia University in the City of New
York
Inventors:
Ronald Breslow, Paul A. Marks, Richard A. Rifkind, Branko Jursic
Abstract: The present invention is directed to a compound in the R configuration about the asymmetric carbon in the following formula:
pharmaceutical compositions containing same and the use thereof in treating CNS disorders in animals.