Abstract: The present invention relates to polypeptide derivatives of dog gastric lipase as obtained by genetic engineering as well as to the nucleotide sequence encoding this recombinant DGL. It also relates to the use of this recombinant DGL for the production of pharmaceutical compositions intended especially for the treatment of pathologies linked to the insufficiency, or even the absence, of secretion of lipases in the body of an individual.
Type:
Grant
Filed:
May 6, 1998
Date of Patent:
December 7, 1999
Assignee:
Warner-Lambert Company
Inventors:
Claire Blanchard, Claude Benicourt, Jean-Louis Junien
Abstract: Benzimidazoles of Formula I below are inhibitors of protein tyrosine kinases, and are useful in treating cellular proliferation. ##STR1## The compounds are especially useful in treating cancer, atherosclerosis, restenosis, and psoriasis.
Type:
Grant
Filed:
August 17, 1998
Date of Patent:
November 23, 1999
Assignee:
Warner-Lambert Company
Inventors:
Diane Harris Boschelli, William Alexander Denny, Annette Marian Doherty, James Marino Hamby, Sonya Shah Khatana, James Bernard Kramer, Brian Desmond Palmer, Howard Daniel Hollis Showalter
Abstract: Sulfonamide compounds are described which are inhibitors of matrix metalloproteinases, particularly stromelysin-1 and gelatinase A (72 kD gelatinase). Also described are methods for the treatment of multiple sclerosis, atherosclerotic plaque rupture, aortic aneurism, heart failure, restenosis, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, arthritis, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes using the compounds.
Type:
Grant
Filed:
May 13, 1998
Date of Patent:
November 2, 1999
Assignee:
Warner-Lambert Company
Inventors:
Daniel F. Ortwine, Claude F. Purchase, Jr., Andrew D. White
Abstract: Diazepinoindoles of formula (I), ##STR1## wherein A is mono- to trisubstituted aryl or heteroaryl, and B is an --OR.sub.1 or --NR.sub.2 R.sub.3 group where R.sub.1, R.sub.2 and R.sub.3 are particularly hydrogen, and racemic forms, enantiomers and pharmaceutically acceptable salts thereof, as phosphodiesterase IV inhibitors, are disclosed.
Type:
Grant
Filed:
October 20, 1998
Date of Patent:
October 26, 1999
Assignee:
Jouveinal
Inventors:
Yves Pascal, Henry Jacobelli, Alain Calvet, Adrian Payne, Svein G. Dahl
Abstract: This invention relates to compounds that are antagonists of dopamine D4 receptors, to methods of treating psychosis and schizophrenia using a compound that is an antagonist of dopamine D4 receptors, and to pharmaceutically acceptable compositions that contain a dopamine D4 receptor antagonist.
Type:
Grant
Filed:
August 11, 1997
Date of Patent:
August 31, 1999
Assignee:
Warner-Lambert Company
Inventors:
Thomas Richard Belliotti, Clifton John Blankley, Suzanne Ross Kesten, Lawrence David Wise, David Juergen Wustrow
Abstract: The present invention relates to a pharmaceutical composition containing a kainate excitatory amino acid antagonist and an uricosuric agent and to a method of treating neurodegenerative diseases using a combination of a kainate excitatory amino acid antagonist and an uricosuric agent.
Type:
Grant
Filed:
March 27, 1998
Date of Patent:
August 24, 1999
Assignee:
Warner-Lambert Company
Inventors:
Christopher Franklin Bigge, Graham Johnson, Charles Price Taylor, Jr., Devin Franklin Welty
Abstract: The present invention provides compounds that inhibit the binding of proteins containing an SH2 domain to cognate phosphorylated proteins. The invention also provides pharmaceutical compositions containing the compounds and methods of inhibiting the binding of proteins containing an SH2 domain to cognate phosphorylated proteins.
Type:
Grant
Filed:
March 31, 1998
Date of Patent:
July 13, 1999
Assignee:
Warner-Lambert Company
Inventors:
Elizabeth A. Lunney, Kimberly S. Para, Mark S. Plummer, Josyula V. N. V. Prasad, Alan R. Saltiel, Tomi Sawyer, Aurash Shahripour, Juswinder Singh, Charles J. Stankovic
Abstract: This invention relates to compounds that are antagonists of dopamine D4 receptors, to methods of treating psychosis and schizophrenia using a compound that is an antagonist of dopamine D4 receptors, and to pharmaceutically acceptable compositions that contain a dopamine D4 receptor antagonist.
Type:
Grant
Filed:
August 11, 1997
Date of Patent:
July 13, 1999
Assignee:
Warner-Lambert Company
Inventors:
Stephen Joseph Johnson, Suzanne Ross Kesten, Lawrence David Wise, David Juergen Wustrow
Abstract: The present invention relates to compounds that are inhibitors of interleukin-1.beta. converting enzyme that have the Formula II ##STR1## This invention also relates to a method of treatment of stroke, inflammatory diseases, septic shock, reperfusion injury, Alzheimer's disease, shigellosis, and to a pharmaceutically acceptable composition that contains a compound that is an inhibitor of interleukin-1.beta. converting enzyme.
Inventors:
Hamish John Allen, Kenneth Dale Brady, Bradley William Caprathe, Paul Galatsis, John Lodge Gilmore, Sheryl Jeanne Hays, Robert Vincent Talanian, Nigel Walker, Joseph Scott Warmus
Abstract: This invention relates to compounds that are antagonists of dopamine D4 receptors, and to methods of treating psychosis and schizophrenia using a compound that is an antagonist of dopamine D4 receptors.
Type:
Grant
Filed:
August 8, 1997
Date of Patent:
June 29, 1999
Assignee:
Warner-Lambert Company
Inventors:
David Thomas Connor, Stephen Joseph Johnson, Suzanne Ross Kesten, Steven Robert Miller, Paul Charles Unangst, Lawrence David Wise
Abstract: This invention relates to compounds that are antagonists of dopamine D4 receptors having Formula I below ##STR1## This invention also relates to methods of treating psychosis and schizophrenia using a compound that is an antagonist of dopamine D4 receptors, and to pharmaceutically acceptable compositions that contain a dopamine D4 receptor antagonist.
Abstract: Novel methods of using thiazolidinone derivatives and related antihyperglycemic agents to treat populations at risk for developing noninsulin-dependent diabetes mellitus (NIDDM) and complications arising therefrom are disclosed In one embodiment, the compounds of the invention are used to treat polycystic ovary syndrome in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus. In another embodiment, the compounds of the invention are used to treat gestational diabetes in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus.
Type:
Grant
Filed:
May 15, 1997
Date of Patent:
February 23, 1999
Assignee:
Warner-Lambert Company
Inventors:
Tammy Antonucci, Dean Lockwood, Rebecca Norris
Abstract: The invention relates to diazepinoindoles of formula: ##STR1## in which R is hydrogen, lower alkyl or lower alkoxy; A is aryl or nitrogen-containing heteroaryl, each of which is optionally substituted by from one to three groups of halogen, lower alkyl, haloalkyl, lower alkoxy and acetamido, or their racemic forms, isomers or pharmaceutically acceptable salts, wherein for the racemic forms of the (S) configuration, A is not phenyl, haloalkyl, or 2-indolyl when R is hydrogen, and for the racemic forms of the (R) configuration, A is not 2-indolyl when R is hydrogen. Also, the invention relates to a method for inhibiting cyclic nucleotide phosphodiesterase activity by administering these compounds to a subject in an amount which is therapeutically effective to inhibit cyclic nucleotide phosphodiesterase activity.
Abstract: New 2-(arylalkenyl)azacycloalkane derivatives which are ligands for sigma receptors, of the formula (I) ##STR1## in which: Ar is aryl or heteroaryl, optionally mono- to trisubstituted,m has the value 1 or 2,n has the value 1 to 3,R is phenyl, or cycloalkyl containing 3 to 7 carbon atoms,their isomers and their addition salts. Medicinal drugs which are antipsychotic agents and are useful in gastroenterology.
Type:
Grant
Filed:
June 7, 1996
Date of Patent:
December 15, 1998
Assignee:
Institut de Recherche Jouveinal
Inventors:
Alain Pierre Calvet, Henry Jacobelli, Jean-Louis Junien, Pierre Riviere, Fran.cedilla.ois-Joseph Roman
Abstract: A method of making (.+-.)-3-(aminomethyl)-5-methylhexanoic acid that comprises condensing isovaleraldehyde with ##STR1## to form primarily ##STR2## reacting the ##STR3## with a cyanide source to form ##STR4## decarboxylating the ##STR5## to form ##STR6## hydrolyzing the ##STR7## with an alkali or alkaline earth metal hydroxide to form an alkali or alkaline earth metal carboxylate salt; and hydrogenating the alkali or alkaline earth metal carboxylate salt to form (.+-.)-3-(aminomethyl)-5-methylhexanoic acid, wherein R.sub.1 and R.sub.2 are the same or different and are hydrogen, C.sub.1 -C.sub.6 alkyl, aryl, benzyl, or C.sub.3 -C.sub.6 cycloalkyl. The present invention also provides a method of making (.+-.
Type:
Grant
Filed:
February 6, 1997
Date of Patent:
November 24, 1998
Assignee:
Warner-Lambert Company
Inventors:
Todd Michel Grote, Brian Keith Huckabee, Thomas Mulhern, Denis Martin Sobieray, Robert Daniel Titus
Abstract: Novel inhibitors of protein:farnesyl transferase enzyme are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in controlling tissue proliferative diseases, including cancer and restenosis.
Type:
Grant
Filed:
June 27, 1996
Date of Patent:
November 3, 1998
Assignee:
Warner-Lambert Company
Inventors:
Gary Louis Bolton, Mark Wallace Creswell, John Cooke Hodges, Michael William Wilson
Abstract: The present invention provides a method of making quinolone carboxylic acids or naphthyridine carboxylic acids in free base form, the method comprising dissolving a quinolone carboxylic acid salt or naphthyridine carboxylic acid salt in a solvent system to form a solution; combining the solution containing the quinolone carboxylic acid salt or naphthyridine carboxylic acid salt with a calcium salt in an amount in the range of about 0.01% to about 5.0% by weight of the quinolone carboxylic acid salt or naphthyridine carboxylic acid salt and a base, the combination resulting in the formation of a precipitate; and collecting the precipitate. Also provided is a solid bulk pharmaceutical chemical composition comprising 7-(3-amino-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-o xoquinoline-3-carboxylic acid or 7-?3-S-(2-S-aminopropionylamino)pyrrolidin-1-yl!-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid; and calcium in an amount in the range of 0.001% to about 1.
Type:
Grant
Filed:
September 30, 1996
Date of Patent:
July 21, 1998
Assignee:
Warner-Lambert Company
Inventors:
Gary Jay Dozeman, Kenneth Thomas Porter, James Norton Wemple
Abstract: The present invention is a pharmaceutical composition having a combination of an uricosuric agent such as probenecid or the like and an excitatory amino acid antagonist useful for treating a disease advantageously affected by treatment with an excitatory amino acid antagonist.
Type:
Grant
Filed:
December 31, 1996
Date of Patent:
June 16, 1998
Assignee:
Warner-Lambert Company
Inventors:
Christopher Franklin Bigge, Graham Johnson, Charles Price Taylor, Jr., Devin Franklin Welty
Abstract: Inhibitors of protein:farnesyl transferase enzyme are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in controlling tissue proliferative diseases, including cancer and restenosis.
Type:
Grant
Filed:
June 21, 1996
Date of Patent:
June 9, 1998
Assignee:
Warner-Lambert Company
Inventors:
Gary Louis Bolton, Alfred Campbell, Richard Gowan, John Cooke Hodges, Donald Hupe, Daniele Leonard, Tomi Sawyer, Judith Sebolt-Leopold, Francis J. Tinney
Abstract: Pharmaceutically useful compounds having ACAT inhibitory activity of the formula ##STR1## wherein n is 0, 1, or 2, for X other than tetrazole and n=2 then R.sub.2 .dbd.R.sub.3 .dbd.H; R.sub.1 is phenyl, substituted phenyl, naphthyl, substituted naphthyl, a heteroaromatic group or a hydrocarbon group having from one to 18 carbon atoms; R.sub.2 and R.sub.3 are hydrogen, halo, hydroxy, alkyl, alkenyl, cycloalkyl, phenyl, substituted phenyl, a heteroaryl, or form a spiroalkyl group; X is a heteromonocyclic 5-membered ring containing one to four heteroatoms, said heteroatoms being nitrogen, oxygen or sulfur, and combination thereof; and R.sub.4 is a hydrocarbon group having from one to 20 carbon atoms are described as well as methods of their manufacture.
Type:
Grant
Filed:
January 21, 1997
Date of Patent:
December 2, 1997
Assignee:
Warner-Lambert Company
Inventors:
Helen Tsenwhei Lee, Patrick Michael O'Brien, Joseph Armand Picard, Claude Forsey Purchase, Jr., Bruce David Roth, Drago Robert Sliskovic, Andrew David White