Abstract: Disclosed are compounds of the formula: wherein X, Q, W and are as defined herein. These compounds are agonists, antagonists or inverse agonists for GABAA brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAA brain receptors and are therefore useful in the diagnosis and treatment of anxiety, depression, Down Syndrome, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABAA receptors in tissue samples.
Type:
Application
Filed:
December 3, 2004
Publication date:
July 14, 2005
Applicant:
Neurogen Corporation, A Corporation of the State of Delaware
Abstract: This invention relates to benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds, all of which may be described by of Formula I The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABAA receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Novel processes for preparing compounds of Formula I are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABAA receptors in tissue sections.
Type:
Grant
Filed:
December 21, 2001
Date of Patent:
July 12, 2005
Assignee:
Neurogen Corporation
Inventors:
Guiying Li, John M. Peterson, Pamela Albaugh, Kevin S. Currie, Guolin Cai, Linda M. Gustavson, Kyungae Lee, Alan Hutchison, Vinod Singh, George D. Maynard, Jun Yuan, Ling Hong Xie, Manuka Ghosh, Nian Liu
Abstract: Substituted tetrahydroisoquinolines and related compounds are provided. Such compounds are ligands that may be used to modulate C5a receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological C5a receptor activation in humans, domesticated companion animals and livestock animals.
Type:
Grant
Filed:
April 15, 2004
Date of Patent:
July 12, 2005
Assignee:
Neurogen Corporation
Inventors:
Kyungae Lee, Scott A. Mitchell, Robert Ohliger, LuYan Zhang, He Zhao, Kevin S. Currie
Abstract: Substituted ring-fused imidazole derivatives that bind to GABAA receptors are provided. Such compounds may be used to modulate ligand binding to GABAA receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals and livestock animals. Compounds provided herein may be administered alone or in combination with one or more other CNS agents to potentiate the effects of the other CNS agent(s). Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for detecting GABAA receptors (e.g., receptor localization studies).
Type:
Grant
Filed:
May 15, 2003
Date of Patent:
July 12, 2005
Assignee:
Neurogen Corporation
Inventors:
George D. Maynard, Jun Yuan, George P. Luke, Kevin Currie
Abstract: Disclosed are compounds of the formula: or pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof, wherein R1, R2, R3, X, Q1 and Q2 are defined herein, which compounds are ligands for neurokinin receptors, in particular NK-3 receptors, and are therefor useful in the treatment of a wide range of diseases or disorders including, but not limited to depression, anxiety, psychosis, obesity, pain, Parkinson's disease, Alzheimer's disease, neurodegenerative diseases, movement disorders, respiratory diseases, inflammatory diseases, neuropathy, immune disorders, migraine, biliary disfunction, and dermatitis.
Type:
Grant
Filed:
April 3, 2002
Date of Patent:
May 17, 2005
Assignee:
Neurogen Corporation
Inventors:
Jun Yuan, George D. Maynard, Alan Hutchison
Abstract: This invention relates to low molecular weight, non-peptidic, non-peptidomimetic, organic molecules that act as modulators of mammalian complement C5a receptors, preferably ones that act as high affinity C5a receptor ligands and also to such ligands that act as antagonists or inverse agonists of complement C5a receptors. Preferred compounds of the invention possess some or all of the following properties in that they are: 1) multi-aryl in structure, 2) heteroaryl in structure, 3) a pharmaceutically acceptable oral dose can provide a detectable in vitro effect, 4) comprise fewer than four or preferably no amide bonds, and 5) capable of inhibiting leukocyte chemotaxis at nanomolar or sub-nanomolar concentrations. This invention also relates to pharmaceutical compositions comprising such compounds and the use of such compounds in treating a variety of inflammatory and immune system disorders. Additionally, this invention relates to the use such compounds as probes for the localization of C5a receptors.
Type:
Grant
Filed:
June 12, 2003
Date of Patent:
April 26, 2005
Assignee:
Neurogen Corporation
Inventors:
Andrew Thurkauf, Xiao-shu He, He Zhao, John Peterson, Xiaoyan Zhang, Robbin Brodbeck, James Krause, George Maynard, Alan Hutchison
Abstract: This invention provides novel human capsaicin receptors and the nucleotide sequences encoding these receptors. Also provided are vectors encoding these receptors and mammalian and non-mammalian cells expressing these vectors. Further provided are assays for identifying compounds that modulate capsaicin receptors and diagnostic assays for capsaicin receptor polymorphisms and aberrant capsaicin receptor expression.
Abstract: This invention relates to cycloalkylpyrrole-3-carboxylic acid derivatives and heterocycloalkylpyrrole-3-carboxylic acid derivatives that bind with high selectively and/or high affinity to the benzodiazepine site of GABAA receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in the treatment of central nervous system (CNS) diseases. This invention also relates to the use of these cycloalkylpyrrole-3-carboxylic acid derivatives and heterocycloalkylpyrrole-3-carboxylic acid derivatives in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the detection of GABAA receptors in tissue samples.
Type:
Grant
Filed:
April 24, 2002
Date of Patent:
March 1, 2005
Assignees:
Pfizer Inc, Neurogen Corporation
Inventors:
Daniel Yohannes, George Maynard, Xiaojun Liu
Abstract: Substituted biaryl amides of Formula I are provided. Such compounds are ligands that may be used to modulate C5a receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological C5a receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.
Type:
Grant
Filed:
March 27, 2003
Date of Patent:
February 22, 2005
Assignee:
Neurogen Corporation
Inventors:
Yang Gao, Alan J. Hutchison, Wallace C. Pringle, Andrew Thurkauf, Taeyoung Yoon, He Zhao
Abstract: Compounds of Formula I are provided, as are methods for their preparation. The variables Z1, Z2, Z3, R4, R5, R6, R7, R8 and Ar in the above formula are defined herein. Such compounds may be used to modulate ligand binding to GABAA receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals and livestock animals. Compounds provided herein may be administered alone or in combination with one or more other CNS agents to potentiate the effects of the other CNS agent(s). Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for detecting GABAA receptors (e.g., receptor localization studies).
Type:
Application
Filed:
July 23, 2004
Publication date:
February 17, 2005
Applicant:
Neurogen Corporation, A Corporation of the State of Delaware
Inventors:
Linghong Xie, Bingsong Han, Yuelian Xu, George Maynard, Bertrand Chenard, Kenneth Shaw, Yang Gao
Abstract: Heterocyclic compounds such as 3,4,5,6-tetrahydro-2,3,10-triaza-benzo[e]azulene-1-carboxylic acid arylamides, 5,7-Dihydro-6H-pyrazolo[3,4-h]quinoline-9-carboxylic acid arylamides, 5,7-Dihydro-6H-pyrazolo[3,4-h]quinazoline-9-carboxylic acid arylamides, 2,4,5,6-Tetrahydro-1,2,6,7-tetraaza-as-indacene-8-carboxylic acid arylamides and related compounds are disclosed. These compounds are highly selective agonists, antagonists or inverse agonists for GABAA brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAA brain receptors and are therefore useful in the treatment of anxiety, depression, sleep and seizure disorders, overdose with benzodiazepine drugs, Alzheimer's dementia, and for enhancement of memory. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Intermediates useful for the synthesis of pyrazolecarboxylic acid arylamides are also provided.
Type:
Grant
Filed:
February 7, 2003
Date of Patent:
February 8, 2005
Assignee:
Neurogen Corporation
Inventors:
George Maynard, Jun Yuan, Stanislaw Rachwal
Abstract: Disclosed are compounds of the formula:
wherein X, Q, W and
are as defined herein. These compounds are agonists, antagonists or inverse agonists for GABAA brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAA brain receptors and are therefore useful in the diagnosis and treatment of anxiety, depression, Down Syndrome, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABAA receptors in tissue samples.
Abstract: The present invention also provides a general method to whereby mono-, bi-, or tricyclic heterocycles may be modified to obtain potent antagonists at the NPY1 receptor.
Type:
Application
Filed:
November 10, 2003
Publication date:
November 18, 2004
Applicants:
NEUROGEN CORPORATION, PFIZER INC.
Inventors:
Raymond F. Horvath, Jennifer N. Tran, Stephane De Lombaert, Kevin J. Hodgetts, Philip A. Carpino, David A. Griffith
Abstract: Disclosed are compounds of the formula:
wherein
R1 represents optionally substituted aryl, heteroaryl, arylalkyl, or cycloalkyl groups; X, Z, and Y are optionally substituted nitrogen or carbon atoms; R3 and R4 are organic or inorganic substitutents which may together form ring structutes; m is zero, one or two; and R5 and R6 are are organic or inorganic substituents;
and the pharmaceutically acceptable addition salts thereof,
which compounds are highly selective partial agonists or antagonists at brain dopamine receptor subtypes or prodrugs thereof and are useful in the diagnosis and treatment of affective disorders such as schizophrenia and depression as well as certain movement disorders such as Parkinsonism.
Type:
Grant
Filed:
March 18, 2002
Date of Patent:
September 28, 2004
Assignee:
Neurogen Corporation
Inventors:
Andrew Thurkauf, Raymond F. Horvath, Jun Yuan, John M. Peterson
Abstract: Disclosed are diaryl piperazines and related compounds. These compounds are selective modulators of capsaicin receptors, including human capsaicin receptors, that are, therefore, useful in the treatment of a chronic and acute pain conditions, itch and urinary incontinence. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of capsaicin receptors and as standards in assays for capsaicin receptor binding and capsaicin receptor mediated cation conductance. Methods of using the compounds in receptor localization studies are given.
Type:
Application
Filed:
March 12, 2004
Publication date:
September 9, 2004
Applicant:
Neurogen Corporation
Inventors:
Rajagopal Bakthavatchalam, Alan Hutchison, Robert W. DeSimone, Kevin J. Hodgetts, James E. Krause, Geoffrey G. White
Abstract: 1 Certain 2-substituted quinazolin-4-ylamine analogues are provided. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.
Type:
Application
Filed:
December 12, 2003
Publication date:
August 12, 2004
Applicant:
Neurogen Corporation
Inventors:
Rajagopal Bakthavatchalam, Charles A. Blum, Harry Brielmann, Timothy M. Caldwell, Stephane De Lombaert, Kevin J. Hodgetts, Xiaozhang Zheng