Abstract: An improved process for the preparation of trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where 1,6-heptadien-4-ol is converted in eight operations to the desired products, as well as an improved process for the preparation of (2R-trans) and trans(.+-.)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrah ydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide by a novel synthesis where 4-methyl-3-oxo-N-phenylpentanamide is converted in eight operations to the desired product or alternatively 4-fluoro-.alpha.-[2-methyl-1-oxopropyl]-.gamma.-oxo-N,.beta.-diphenylbenze nebutaneamide is converted in one step to the desired product, and additionally, 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 from (R)-4-cyano-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]butanoic acid, as well as other valuable intermediates used in the processes.
Type:
Grant
Filed:
November 14, 1991
Date of Patent:
June 23, 1992
Assignee:
Warner-Lambert Company
Inventors:
Donald E. Butler, Carl F. Deering, Alan Millar, Thomas N. Nanninga, Bruce D. Roth
Abstract: Substituted indoles 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.
Abstract: Substituted 1,2,3,6-tetrahydropyridines 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, antipsychotic, and antihypertensive agents as well as for treating hyperprolactinaemia-related conditions and central nervous system disorders.
Type:
Grant
Filed:
June 28, 1991
Date of Patent:
June 9, 1992
Assignee:
Warner-Lambert Company
Inventors:
Bradley W. Caprathe, Juan C. Jaen, Lawrence D. Wise
Abstract: Substituted tetrahydropyridines 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, antipsychotic, and antihypertensive agents as well as for treating hyperprolactinaemia-related conditions and central nervous system disorders.
Type:
Grant
Filed:
June 17, 1991
Date of Patent:
June 2, 1992
Assignee:
Warner-Lambert Co.
Inventors:
Juan C. Jaen, David G. Nickell, Donna M. Reynolds, Sarah J. Smith, Lawrence D. Wise, David J. Wustrow
Abstract: An improved process for the preparation of (4R-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate is described where a hydroxy ester derivative is converted in two steps to the desired product, as well as valuable intermediates used in the process.
Abstract: An improved process for the preparation of trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where 1,6-heptadien-4-ol is converted in eight operations to the desired products, as well as an improved process for the preparation of (2R-trans) and trans-(.+-.)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetra hydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]1H-pyrrole-3-carboxamide by a novel synthesis where 4-methyl-3-oxo-N-phenylpentanamide is converted in eight operations to the desired product or alternatively 4-fluoro-.alpha.-[2-methyl-1-oxopropyl]-.gamma.-oxo-N,.beta.-diphenylbenze nebutaneamide is converted in one step to the desired product, and additionally, 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 from (R)-4-cyano-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]butanoic acid, as well as other valuable intermediates used in the processes.
Type:
Grant
Filed:
October 9, 1990
Date of Patent:
March 17, 1992
Assignee:
Warner-Lambert Company
Inventors:
Donald E. Butler, Carl F. Deering, Alan Millar, Thomas N. Nanninga, Bruce D. Roth
Abstract: The instant invention concerns a novel process for the preparation of 1-aminomethyl-1-cyclohexaneacetic acid (gabapentin), a known compound useful for treating certain cerebral diseases such as epilepsy and dizziness.
Type:
Grant
Filed:
August 21, 1990
Date of Patent:
February 25, 1992
Assignee:
Godecke Aktiengesellschaft
Inventors:
Wolfram Geibel, Johannes Hartenstein, Wolfgang Herrmann, Joachim Witzke
Abstract: Substituted piperazines 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, antipsychotic, and antihypertensive agents as well as for treating hyperprolactinaemia-related conditions and central nervous system disorders.
Type:
Grant
Filed:
September 20, 1990
Date of Patent:
February 18, 1992
Assignee:
Warner-Lambert Company
Inventors:
Juan C. Jaen, David G. Nickell, Donna M. Reynolds, Sarah J. Smith, Lawrence D. Wise, David J. Wustrow
Abstract: An improved process for the preparation of [1S-(1R*,2S*,3R*)]-N-(4-morpholinylsulfonyl)-L-phenylalanyl-3-(2-amino-4-t hiazolyl)-N-[(1-cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl]-L-alaninamid e is described where the key intermediate, 3-(2-amino-4-thiazolyl)-L-alanine is converted without protecting the aminothiazole group to the desired compound, as well as valuable intermediates used in the process.
Type:
Grant
Filed:
April 23, 1991
Date of Patent:
February 18, 1992
Assignee:
Warner-Lambert Company
Inventors:
Daniel T. Belmont, Valerie Hendrickson, Mark J. Hoekman
Abstract: Processes for the preparation of cyclic amino acid derivatives useful in the treatment of cerebral diseases such as epilepsy are disclosed. Novel intermediates useful in processes are also disclosed.
Type:
Grant
Filed:
August 21, 1990
Date of Patent:
November 26, 1991
Assignee:
Godecke Aktiengesellschaft
Inventors:
Klaus Steiner, Wolfgang Herrmann, Gunter Crone, Charles S. Combs
Abstract: Substituted furans and derivatives thereof are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as centrally acting muscarinic agents and are useful as analgesic agents for the treatment of pain, as sleep aids and as agents for treating the symptoms of senile dementia, Alzheimer's disease, Huntington's chorea, tardive, dyskinesia, hyperkinesia, mania, or similar conditions of cerebral insufficiency characterized by decreased cerebral acetylcholine production or release.
Abstract: Substituted-hetero-cyclopentanones and cyclopentenones and derivatives thereof are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as centrally acting muscarinic agents and are useful as analgesic agents for the treatment of pain, as sleep aids and as agents for treating the symptoms of senile dementia, Alzheimer's disease, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, or similar conditions of cerebral insufficiency characterized by decreased cerebral acetylcholine production or release.
Abstract: Substituted isoxazolidin-3-ones and derivatives thereof are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as centrally acting muscarinic agents and are useful as analgesic agents for the treatment of pain, as sleep aids and as agents for treating the symptoms of senile dementia, Alzheimer's disease, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, or similar conditions of cerebral insufficiency characterized by decreased cerebral acetylcholine production or release.
Abstract: Oxazolidin-2-ones and 1,2,4-oxadiazolin-5-ones substituted in the 4-position of the oxazolidin-2-one ring and the 3-position of the 1,2,4-oxadiazolin-5-one ring with a 5- or 6-member heteroaromatic, a bicyclic heteroaromatic group or a 5- or 6-member heterocyclic group either directly or via a one or two carbon bridge and derivatives thereof are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as centrally acting muscarinic agents and are useful as analgesic agents for the treatment of pain, as sleep aids and as agents for treating the symptoms of senile dementia, Alzheimer's disease, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, or similar conditions of cerebral insufficiency characterized by decreased cerebral acetycholine production or release.
Abstract: An improved process for the preparation of statine, the phenyl analog of statine, the cyclohexyl analog of statine and derivatives thereof is described, as well as other valuable intermediates used in the process.
Abstract: Novel large-ring diamine platinum(II) and platinum(IV) complexes which are useful in inhibiting the growth of malignant neoplasms, as well as novel pharmaceutical compositions and methods of use, as well as processes for their manufacture are herein described.
Abstract: Substituted cyclohexanols and 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, antipsychotic, and antihypertensive agents as well as for treating hyperprolactinaemia-related conditions and central nervous system disorders.
Type:
Grant
Filed:
May 2, 1990
Date of Patent:
September 10, 1991
Assignee:
Warner-Lambert Co.
Inventors:
Bradley W. Caprathe, Juan C. Jaen, Sarah J. Smith, Lawrence D. Wise
Abstract: Substituted tetrahydropyridines 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, antipsychotic, and antihypertensive agents as well as for treating hyperprolactinaemia-related conditions and central nervous system disorders.
Type:
Grant
Filed:
September 20, 1990
Date of Patent:
September 3, 1991
Assignee:
Warner-Lambert Co.
Inventors:
Juan C. Jaen, David G. Nickell, Donna M. Reynolds, Sarah J. Smith, Lawrence D. Wise, David J. Wustrow
Abstract: An improved process for the preparation of trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where 1,6-heptadien-4-ol is converted in eight operations to the desired products, as well as an improved process for the preparation of (2R-trans) and trans-(.+-.)-5-(4-fluorophenyl)-2-(1-methylethyl)-N-4-diphenyl-1-[2-tetrah ydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide by a novel synthesis where 4-methyl-3-oxo-N-phenylpentanamide is converted in eight operations to the desired product or alternatively 4-fluoro-.alpha.-[2-methyl-1-oxopropyl]-.gamma.-oxo-N,.beta.-diphenylbenze nebutaneamide is converted in one step to the desired product, and additionally, 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 from (R)-4-cyano-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]butanoic acid, as well as other valuable intermediates used in the processes.
Type:
Grant
Filed:
February 1, 1989
Date of Patent:
March 26, 1991
Assignee:
Warner-Lambert Company
Inventors:
Donald E. Butler, Carl F. Deering, Alan Millar, Thomas N. Nanninga, Bruce D. Roth
Abstract: Novel prodrugs or depot derivatives of 1,2,3,4-tetrahydro-9-acridinamine are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as analgesic agents for the treatment of pain, as sleep aids and as agents for treating the symptoms of senile dementia, Alzheimer's disease, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, or similar conditions of cerebral insufficiency characterized by decreased cerebral acetylcholine production or release.
Type:
Grant
Filed:
July 31, 1989
Date of Patent:
March 12, 1991
Assignee:
Warner-Lambert Company
Inventors:
Jeffrey A. Kester, Walter H. Moos, Anthony J. Thomas