Abstract: Novel combinations of inhibitors of protein farnesyltransferase enzymes and HMG CoA reductases enzymes are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in preventing or treating cancer, restenosis, psoriasis, endometriosis, atherosclerosis, or viral infections.
Abstract: An improved process for the preparation of 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide by a novel synthesis is described where methyl cyanoacetate is converted in eight operations or fewer to the desired product, as well as other valuable intermediates used in the process.
Type:
Grant
Filed:
December 17, 2001
Date of Patent:
November 5, 2002
Assignee:
Warner-Lambert Company
Inventors:
Donald Eugene Butler, Randall Lee DeJong, Jade Douglas Nelson, Michael Gerard Pamment, Timothy Lee Stuk
Abstract: An improved process for the preparation of cis-1,3-diols is described where a beta hydroxy ketone is treated with a trialkylborane or dialkylalkoxyborane or a mixture of a trialkylborane and a dialkylalkoxyborane followed by recovery and reuse of the alkylborane species to convert additional beta hydroxy ketone to the cis-1,3-diol.
Type:
Grant
Filed:
June 16, 2000
Date of Patent:
August 13, 2002
Assignee:
Warner-Lambert Company
Inventors:
Robert Lee Bosch, Richard Joseph McCabe, Thomas Norman Nanninga, Robert Joseph Stahl
Abstract: Novel polymer-supported quenching reagents of Formula (I): P-L-Q, wherein P is a polymer of low chemical reactivity which is soluble or insoluble; Q is one or more quenching reagents, or an acid or base addition salts thereof, that are capable of selective covalent reaction with unwanted byproducts, or excess reagents; and L is one or more chemically robust linkers that join P and Q; are described, as well as methods for their preparation and methods for their use in the rapid purification of synthetic intermediates and products in organic synthesis, combinatorial chemistry and automated organic synthesis.
Type:
Grant
Filed:
October 15, 1998
Date of Patent:
October 23, 2001
Assignee:
Warner Lambert Company
Inventors:
Gary L. Bolton, Richard J. Booth, Mark W. Creswell, John C. Hodges, Joseph S. Warmus, Michael W. Wilson
Abstract: A novel process for the preparation of amorphous atorvastatin is described where crystalline Form I atorvastatin is dissolved in a non-hydroxylic solvent and after removal of the solvent affords amorphous atorvastatin.
Abstract: Described are compositions and a method of inhibiting epidermal growth factor receptor tyrosine kinase by treating, with an effective inhibiting amount, a mammal, in need thereof, a compound of Formula II:
where:
any two continguous positions in positions A-E taken together can be a single heteroatom selected from the group consisting of nitrogen, oxygen or sulfur, in which case the other two remaining atoms must be carbon; the remaining substituents are disclosed in the specification
Type:
Grant
Filed:
November 13, 1998
Date of Patent:
July 24, 2001
Assignee:
Warner-Lambert Company
Inventors:
Alexander James Bridges, William Alexander Denny, David Fry, Alan Kraker, Robert Frederick Meyer, Gordon William Rewcastle, Andrew Mark Thompson
Abstract: The invention provides compounds of Formula I ##STR1## that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.
Abstract: A novel crystalline form of [(R-(R*,R*)]-2-(4-fluorophenyl)-.beta.,.delta.-dihydroxy-5-(1-methylethyl) -3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt designated Form III is characterized by its X-ray powder diffraction and/or solid state NMR is described, as well as methods for the preparation and pharmaceutical composition of the same, which is useful as an agent for treating hyperlipidemia and hypercholesterolemia.
Abstract: A process for the preparation of amorphous atorvastatin is described where crystalline Form I atorvastatin is dissolved in a non-hydroxylic solvent and after removal of the solvent affords amorphous atorvastatin.
Abstract: Novel 4-substituted amino pyrido [3,2-d]pyrimidine inhibitors of epidermal growth factor receptor family of tyrosine kinases are described, as well as pharmaceutical compositions of the same, which are useful in treating proliferative diseases such as cancer, synovial pannus invasion in arthritis, psoriasis, vascular restenosis and angiogenesis and additionally useful in the treatment of pancreatitis and kidney disease as well as a contraceptive agent.
Type:
Grant
Filed:
March 6, 1997
Date of Patent:
July 4, 2000
Assignee:
Warner-Lambert Company
Inventors:
Alexander James Bridges, William Alexander Denny, David Fry, Alan Kraker, Robert Frederick Meyer, Gordon William Rewcastle, Andrew Mark Thompson
Abstract: The present invention concerns cyclic amino acids of formula ##STR1## substantially free from the lactam ##STR2## wherein n is an integer of from 4 to 6, a process for the preparation thereof, compositions containing the compounds and methods of using them.
Type:
Grant
Filed:
January 25, 1995
Date of Patent:
April 25, 2000
Assignee:
Godecke Aktiengesellschaft
Inventors:
Helmut Augart, Uwe Gebhardt, Wolfgang Herrmann
Abstract: Substituted histidine compounds of formula (I) are described as well as methods for the preparation and pharamaceutical compositions of same, which are useful as inhibitors of protein famesyltransferase and for the treatment of proliferative diseases including cancer, restenosis, and psoriasis, and as antiviral agents.
Type:
Grant
Filed:
July 2, 1998
Date of Patent:
December 28, 1999
Assignee:
Warner-Lambert Company
Inventors:
Annette M. Doherty, James S. Kaltenbronn, Daniele Leonard, John Quin, III, Jeffrey D. Scholten
Abstract: Aromatic keto-acid compounds and derivatives are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as inhibitors of matrix metalloproteinases, particularly gelatinase A (72 kD gelatinase) and stromelysin-1 and for the treatment of multiple sclerosis, atherosclerotic plaque rupture, aortic aneurism, heart failure, restenosis, periodontal disease, corneal ulceration, treatment of burns, decubital ulcers, wound healing, cancer, arthrities, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes.
Type:
Grant
Filed:
June 8, 1998
Date of Patent:
December 28, 1999
Assignee:
Warner Lambert Company
Inventors:
Donald Hupe, Linda Lea Johnson, Daniel Fred Ortwine, Claude Forsey Purchase, Jr., Andrew David White, Qi-Zhuang Ye
Abstract: The invention is an improved process for the preparation of a compound of formula I wherein R and R.sup.1 are each independently alkyl of from 1 to 3 carbon atoms; and R.sup.2 is alkyl of from 1 to 8 carbon atoms.
Abstract: Substituted cyclohexylamines and derivatives thereof are described, as well as methods for the preparation and pharmaceutical composition of same, which are useful as central nervous system agents and are particularly useful as dopaminergic, serotonergic, antipsychotic, and anxiolytic agents.
Type:
Grant
Filed:
March 20, 1998
Date of Patent:
November 2, 1999
Assignee:
Warner-Lambert Company
Inventors:
Thomas R. Belliotti, Suzanne R. Kesten, Thomas A. Pugsley, David J. Wustrow
Abstract: A method for the preparation and purification of compounds using a novel support, a tetrabenzo[a,c,g,i]fluorene group (Tbf) comprising reacting a building block (A) containing a Tbf group (Tbf-A), with a second building block (B), to afford an intermediate compound (Tbg-A-B) followed by purifying the intermediate compound by adsorption on a carbon support, removing the intermediate compound from the support with a solvent and repeating the previous reactions using the required number of building blocks to synthesize the compounds followed by removal of the Tbf group to afford the desired compounds.
Type:
Grant
Filed:
March 25, 1998
Date of Patent:
November 2, 1999
Assignee:
Warner-Lambert Company
Inventors:
Sheila Helen DeWitt, Robert Ramage, Alasdair Arthur MacDonald
Abstract: Substituted piperazines and piperidines and derivatives thereof are described, as well as methods for the preparation and pharmaceutical composition of same, which are useful as central nervous system agents and are particularly useful as dopamine antagonists and antipsychotic agents.
Type:
Grant
Filed:
December 19, 1997
Date of Patent:
October 12, 1999
Assignee:
Warner-Lambert Company
Inventors:
Shelly A. Glase, Terri S. Purchase, Lawrence D. Wise
Abstract: Tricyclic compounds are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as inhibitors of matrix metalloproteinases, particularly gelatinase A (72 kD gelatinase) and stromelysin-1 and for the treatment of multiple sclerosis, atherosclerotic plaque rupture, aortic aneurism, heart failure, restenosis, periodontal disease, corneal ulceration, cancer metastasis, tumor angiogenesis, arthritis, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes.
Type:
Grant
Filed:
May 20, 1997
Date of Patent:
September 28, 1999
Assignee:
Warner-Lambert Company
Inventors:
Donald Hupe, Linda Lea Johnson, Joseph Armand Picard, Andrew David White, Qi-Zhuang Ye
Abstract: A method for the solid phase preparation of an amine by a novel synthesis is described where a diol is monoalkylated with a chloromethyl resin followed by reaction with N,N'-carbonyldimidazole to afford a resin-bound tertiary-alkoxycarbonyl-imidazole which is subsequently N-alkylated and then sequentially treated with appropriate building blocks and reagents to afford a resin-bound amine which affords the desired amine after treatment with an acid as well as other valuable intermediates used in the process.
Type:
Grant
Filed:
October 7, 1998
Date of Patent:
August 3, 1999
Assignee:
Warner-Lambert Company
Inventors:
John Cooke Hodges, Andres Sergio Hernandez