Abstract: A method for the multiple, simultaneous synthesis of compounds comprising the steps of: 1) providing an apparatus comprising a plurality of reaction tubes having filter members on their lower ends, a reservoir member for receiving the filter member, a holder member having a plurality of apertures for supporting the reaction tubes, and a manifold member adjacent to the holder member and enclosing the upper ends of the reaction tubes; 2) charging the apparatus with reactants required for synthesis; 3) synthesizing the compounds in solution; or optionally 4) cleaving the compounds from a solid support within the apparatus.
Type:
Grant
Filed:
April 28, 1995
Date of Patent:
March 18, 1997
Assignee:
Warner-Lambert Company
Inventors:
Donna R. Cody, Sheila H. H. DeWitt, John C. Hodges, John S. Kiely, Walter H. Moos, Michael R. Pavia, Bruce D. Roth, Mel C. Schroeder, Charles J. Stankovic
Abstract: An improved process for the preparation of 3-chlorobenzo[b]thiophene-2-carbonyl chlorides is described where a cinnamic acid is converted in the presence of thionyl chloride and a 4-N,N'-disubstituted aminopyridine in one step to the desired product.
Abstract: An apparatus and method which provides a suitable location for multiple, simultaneous synthesis of compounds. The apparatus consists of: a reservoir block having a plurality of wells; a plurality of reaction tubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which my have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable plate with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold.
Type:
Grant
Filed:
June 5, 1995
Date of Patent:
January 14, 1997
Assignee:
Warner-Lambert Company
Inventors:
Sheila H. H. DeWitt, John S. Kiely, Michael R. Pavia, Mel C. Schroeder, Charles J. Stankovic
Abstract: An apparatus and method which provides a suitable location for multiple, simultaneous synthesis of compounds. The apparatus consists of: a reservoir block having a plurality of wells; a plurality of reaction tubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which may have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable plate with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold.
Type:
Grant
Filed:
June 5, 1995
Date of Patent:
December 10, 1996
Assignee:
Warner-Lambert Company
Inventors:
Sheila H. H. DeWitt, John S. Kiely, Michael R. Pavia, Mel C. Schroeder, Charles J. Stankovic
Abstract: An apparatus and method which provides a suitable location for multiple, simultaneous synthesis of compounds. The apparatus consists of: a reservoir block having a plurality of wells; a plurality of reaction tubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which may have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable plate with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold.
Type:
Grant
Filed:
June 5, 1995
Date of Patent:
October 22, 1996
Assignee:
Warner-Lambert Company
Inventors:
Sheila H. H. DeWitt, John S. Kiely, Michael R. Pavia, Mel C. Schroeder, Charles J. Stankovic
Abstract: An apparatus and method which provides a suitable location for multiple, simultaneous synthesis of compounds. The apparatus consists of: a reservoir block having a plurality of wells; a plurality of reaction cubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which may have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable place with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold.
Type:
Grant
Filed:
June 5, 1995
Date of Patent:
October 15, 1996
Assignee:
Warner-Lambert Company
Inventors:
Sheila H. H. DeWitt, John S. Kiely, Michael R. Pavia, Mel C. Schroeder, Charles J. Stankovic
Abstract: Sulfonylquinolines 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 antiobesity agents and for the treatment of hypertension.
Abstract: Novel antagonists of endothelin are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, metabolic, endocrinological, neurological disorders especially cerebral vasospasm, stroke, and head injury, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease, restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, and diabetes.
Type:
Grant
Filed:
June 30, 1994
Date of Patent:
August 27, 1996
Assignee:
Warner-Lambert Company
Inventors:
Wayne L. Cody, Annette M. Doherty, John G. Topliss
Abstract: An improved process for the preparation of trans-6- 2-(substituted-pyrrole-1-yl)alkyl!pyran-2-ones by a novel synthesis is described where .alpha.-metalated N,N-disubstituted acetamide is converted in seven operations to the desired products, and specifically, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N, 4-diphenyl-1- 2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl!-1H-pyrrol e-3-carboxamide, as well as other valuable intermediates used in the processes and prodrugs which are bioconverted to hypolipidemic and hypocholesterolemic agents and pharmaceutical compositions of the same.
Type:
Grant
Filed:
May 15, 1995
Date of Patent:
April 23, 1996
Assignee:
Warner-Lambert Company
Inventors:
Donald E. Butler, Tung Van Le, Thomas N. Nanninga
Abstract: An improved process for the preparation of 9-(.beta.-D-arabinofuranosyl)adenine, 5'-phosphate, is described where dried 9-(.beta.-D-arabinofuranosyl)adenine is reacted with triethyl phosphate and phosphorous oxychloride in dichloromethane and the reaction mixture hydrolyzed and excess hydrogen chloride removed with propylene oxide as the acid scavenger. This process gives a yield of about 70-85%, which is nearly double the yields of the prior art.
Abstract: An improved process for the preparation of trans-6-[2-(substituted-pyrrole-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where .alpha.-metalated N,N-disubstituted acetamide is converted in seven operations to the desired products, and specifically, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahy dro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide, as well as other valuable intermediates used in the processes and prodrugs which are bioconverted to hypolipidemic and hypocholesterolemic agents and pharmaceutical compositions of the same.
Type:
Grant
Filed:
May 15, 1995
Date of Patent:
February 6, 1996
Assignee:
Warner-Lambert Company
Inventors:
Donald E. Butler, Tung Van Le, Thomas N. Nanninga
Abstract: An improved process for the preparation of trans-6-[2-(substituted-pyrrole-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where .alpha.-metalated N,N-disubstituted acetamide is converted in seven operations to the desired products, and specifically, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahy dro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide, as well as other valuable intermediates used in the processes and prodrugs which are bioconverted to hypolipidemic and hypocholesterolemic agents and pharmaceutical compositions of the same.
Type:
Grant
Filed:
May 15, 1995
Date of Patent:
February 6, 1996
Assignee:
Warner-Lambert Company
Inventors:
Donald E. Butler, Tung V. Le, Thomas N. Nanninga
Abstract: Benzimidazoles and imidazopyridines 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 antipsychotic agents and for the treatment of disorders which respond to dopaminergic blockade including psychotis depression, substance abuse, and compulsive disorders.
Type:
Grant
Filed:
May 10, 1994
Date of Patent:
January 23, 1996
Assignee:
Warner-Lambert Company
Inventors:
Dennis M. Downing, Shelly A. Glase, Stephen J. Johnson, Lawrence D. Wise, Jonathan L. Wright
Abstract: Substituted phenoxyhydroxy amines and derivatives thereof are described as well as methods for the preparation and pharmaceutical compositions of same, which are central nervous system agents useful in the treatment of neurological disorders including traumatic brain surgery, stroke, migraine, acute and chronic pain, epilepsy, Parkinson's disease, Alzheimer's disease, amyotropic lateral sclerosis, multiple sclerosis, psychosis, and depression.
Abstract: An improved process for the preparation of trans-6-[2-(substituted-pyrrole-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where .alpha.-metalated N,N-disubstituted acetamide is converted in seven operations to the desired products, and specifically, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahy dro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H pyrrole-3-carboxamide, as well as other valuable intermediates used in the processes and prodrugs which are bioconverted to hypolipidemic and hypocholesterolemic agents and pharmaceutical compositions of the same.
Type:
Grant
Filed:
January 18, 1995
Date of Patent:
November 28, 1995
Assignee:
Warner-Lambert Company
Inventors:
Donald E. Butler, Tung V. Le, Thomas N. Nanninga
Abstract: Substituted tetrahydropyridines and hydroxypiperidines and derivatives thereof are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as central nervous system agents and are particularly useful as dopaminergic, antipsychotic, and antihypertensive agents as well as for treating hyperprolactinaemia-related conditions and central nervous system disorders.
Type:
Grant
Filed:
September 29, 1993
Date of Patent:
November 14, 1995
Assignee:
Warner-Lambert Company
Inventors:
Shelly Glase, Juan C. Jaen, Sarah J. Smith, Lawrence D. Wise
Abstract: Novel cyclic amino acids which are useful in preparing biologically active peptides as well as a process for the preparation of D and L enantiomers of the cyclic amino acids are described where an N-protected derivative of the racemic cyclic amino acid is treated with (-)cinchonidine and the resulting salt resolved into the desired enantiomers, as well as derivatives thereof and valuable intermediates used in the process.
Type:
Grant
Filed:
September 8, 1994
Date of Patent:
September 12, 1995
Assignee:
Warner-Lambert Company
Inventors:
Vladimir Beylin, Huai G. Chen, Om P. Goel, Mark E. Marlatt, John G. Topliss
Abstract: Substituted tetrahydropyridines and piperidinecarboxylic acids and derivatives thereof are described, as well as methods for the preparation and pharmaceutical composition of same, which muscarinic antagonists are useful as agents for inhibiting gastric acid release, for treating bradycardia, bronchoconstriction, urinary incontinence, atonic conditions of the gut and bladder, Parkinson's disease, dystonias, and Alzheimer's disease.
Type:
Grant
Filed:
September 24, 1993
Date of Patent:
August 29, 1995
Assignee:
Warner-Lambert Company
Inventors:
Corinne E. Augelli-Szafran, Juan C. Jaen, Roy Schwarz, Anthony J. Thomas
Abstract: An improved process for the preparation of trans-6-[2-(substituted-pyrrole-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where .alpha.-metalated N,N-disubstituted acetamide is converted in seven operations to the desired products, and specifically, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahy dro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide, as well as other valuable intermediates used in the processes and prodrugs which are bioconverted to hypolipidemic and hypocholesterolemic agents and pharmaceutical compositions of the same.
Type:
Grant
Filed:
October 14, 1994
Date of Patent:
August 29, 1995
Assignee:
Warner-Lambert Company
Inventors:
Donald E. Butler, Tung V. Le, Thomas N. Nanninga
Abstract: Neurotensin antagonists 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 antipsychotic agents and as agents to treat Parkinson's disease and gastrointestinal disorders.
Type:
Grant
Filed:
April 7, 1994
Date of Patent:
July 4, 1995
Assignee:
Warner-Lambert Company
Inventors:
Stephen J. Johnson, Suzanne R. Kesten, Lawrence D. Wise, David J. Wustrow