Abstract: (Heterocycloalkyl)methyl azole derivatives of Formula (I) are provided: Formula I wherein A is oxygen, sulfur, or NR; J and K and each L are independently oxygen, sulfur, NH, or CH2; and the remaining variables are defined herein. Such compounds are modulators of C5a receptors, and preferably bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. Also provided herein are pharmaceutical compositions comprising such compounds, as well as methods for using such compounds in treating a variety of inflammatory and immune system disorders.
Type:
Application
Filed:
June 30, 2004
Publication date:
July 13, 2006
Applicant:
Neurogen Corporation
Inventors:
Suoming Zhang, He Zhao, Yang Gao, Andrew Thurkauf, George Maynard, Bertrand Chenard, Robert Ohliger, John Peterson
Abstract: 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:
Grant
Filed:
January 17, 2003
Date of Patent:
July 11, 2006
Assignee:
Neurogen Corporation
Inventors:
Rajagopal Bakthavatchalam, Charles A. Blum, Harry Brielmann, Timothy M. Caldwell, Stephane De Lombaert, Kevin J. Hodgetts, Xiaozhang Zheng
Abstract: This invention relates to novel compounds, compositions, and methods for the treatment of physiological disorders associated with an excess of neuropeptide Y.
Type:
Grant
Filed:
November 10, 2003
Date of Patent:
July 11, 2006
Assignees:
Neurogen Corp., Pfizer, Inc.
Inventors:
Raymond F. Horvath, Jennifer Tran, Stéphane De Lombaert, Kevin J. Hodgetts, Philip A. Carpino, David A. Griffith
Abstract: The invention provides compounds of Formula (I) that bind to GABAA receptors. In the above formula, variables 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).
Abstract: Methods are provided that are useful in assaying compounds for cognitive enhancing properties, anxiolytic properties, hypnotic properties, or antidepressant properties. These methods involve determining the in vitro efficacy and EC50 of the compounds at defined series of cloned GABAA subtype receptors composed of specific variants of ?, ?, and ? subunits in order to develop and an activity profile for each compound. Optionally, the binding affinities of the compounds at GABAA receptors are also determined. As an additional step the in vivo effects of the compounds may be tested in animal models.
Type:
Grant
Filed:
November 9, 2001
Date of Patent:
June 13, 2006
Assignee:
Neurogen Corporation
Inventors:
John Tallman, Dorothy Gallager, Kenneth Shaw, Geoffrey White, Marci Crandall, James Cassella, Lavanya Rajachandran, Pamela Albaugh
Abstract: Disclosed are compounds of the formula: and the pharmaceutically acceptable salts thereof, wherein W, Q, X, X1, Y and Z are as defined herein. These compounds bind with high selectivity and/or high affinity to the benzodiazepine site of GABAA receptors and are therefore useful in the treatment of central nervous system (CNS) diseases and as probes for the localization of GABAA receptors in tissue samples. Also disclosed are intermediates useful in the preparation of these compounds.
Type:
Grant
Filed:
January 28, 2003
Date of Patent:
May 30, 2006
Assignee:
Neurogen Corporation
Inventors:
Jun Yuan, Pamela Albaugh, Kenneth Shaw, Alan Hutchison
Abstract: Substituted biaryl quinolin-4-ylamine analogues of Formula I 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 such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.
Type:
Application
Filed:
October 12, 2005
Publication date:
May 25, 2006
Applicant:
Neurogen Corporation
Inventors:
Rajagopal Bakthavatchalam, Timothy Caldwell, Bertrand Chenard, Kevin Hodgetts, Scott Capitosti
Abstract: Substituted biphenyl-4-carboxylic acid arylamide analogues capable of modulating receptor activity, are provided. Such ligands may be used to modulate receptor activity in vivo or in vitro, and are particularly useful in the treatment of pain and other conditions associated with receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for receptor localization studies.
Type:
Application
Filed:
December 19, 2003
Publication date:
May 11, 2006
Applicant:
Neurogen Corporation
Inventors:
Rajagopal Bakthavatchalam, Charles Blum, Harry Brielmann, James Darrow, Stephane DeLombaert, Taeyoung Yoon, Xiaozhang Zheng
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:
June 14, 2004
Date of Patent:
May 9, 2006
Assignee:
Neurogen Corporation
Inventors:
Jun Yuan, George Maynard, Alan Hutchison
Abstract: Disclosed are compounds of formula (I) or pharmaceutically acceptable non-toxic salts or pharmaceutically acceptable solvates thereof wherein: (II) represents (a), (b), (c) or (d) and W, X, Y, A, B, C, D, E are variables as described herein. These compounds are highly selective agonists or antagonists at NK3 receptors or prodrugs thereof. The novel tachykinin NK-3 receptor antagonists contained in this invention have potential utility in the treatment of a broad array of disorders and diseases of the central nervous system (CNS) and periphery in mammals in which activation of NK-3 receptors is of importance.
Type:
Grant
Filed:
March 10, 2000
Date of Patent:
May 2, 2006
Assignee:
Neurogen Corporation
Inventors:
Jun Yuan, George Maynard, Alan Hutchison
Abstract: Substituted 2-cyclohexyl-4-phenyl-1H-imidazole derivatives capable of modulating NPY5 receptor activity, are provided. Such compounds may be used to modulate NPY binding to NPY5 receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of disorders (e.g., eating disorders such as obesity or bulimia, psychiatric disorders, diabetes and cardiovascular disorders such as hypertension) in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such compounds for detecting NPY5 receptors.
Type:
Grant
Filed:
October 21, 2002
Date of Patent:
April 25, 2006
Assignee:
Neurogen Corporation
Inventors:
Charles A. Blum, Harry L. Brielmann, Stephane De Lombaert, Xiaozhang Zheng
Abstract: Substituted 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 2, 2003
Date of Patent:
April 18, 2006
Assignee:
Neurogen Corporation
Inventors:
George Maynard, Linda M. Gustavson, Bingsong Han
Abstract: Disclosed are compounds of the formula and the pharmaceutically acceptable salts thereof where the variables R1, R2, A, R4, R5, R6, R6?, n, and W are defined herein. These compounds bind to the benzodiazepine site of GABAA receptors are provided and, therefore can 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.
Type:
Grant
Filed:
March 9, 2004
Date of Patent:
March 7, 2006
Assignee:
Neurogen Corporation
Inventors:
Guiying Li, John Peterson, Pamela Albaugh
Abstract: Arylpyrazine compounds are provided, including arylpyrazines that can bind with high affinity and high selectivity to CRF1 receptors, including human CRF1 receptors. The invention thus includes methods for treatment of disorders and diseases associated with CRF1 receptors, including CNS-related disorders and diseases, particularly affective disorders and diseases, and acute and chronic neurological disorders and diseases.
Type:
Grant
Filed:
February 16, 2001
Date of Patent:
February 7, 2006
Assignee:
Neurogen Corporation
Inventors:
Taeyoung Yoon, Ping Ge, Raymond F. Horvath, Stephane DeLombaert, Kevin J. Hodgetts, Dario Doller, Cunyu Zhang
Abstract: Substituted imidazolylmethyl pyridine and pyrazine 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 7, 2003
Date of Patent:
January 3, 2006
Assignee:
Neurogen Corporation
Inventors:
Linghong Xie, Manuka Ghosh, George Maynard
Abstract: Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein the A, B, C, D, X, R1, R2, R3, R4, R5, and R6, are variables defined herein, which 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 diagnosis and treatment of anxiety, Down Syndrome, sleep, cognitive and seizure disorders, depression, overdose with benzodiazepine drugs, and enhancement of memory and alertness.
Type:
Grant
Filed:
June 30, 2003
Date of Patent:
December 6, 2005
Assignee:
Neurogen Corporation
Inventors:
Robert W. DeSimone, Alan Hutchison, Kenneth Shaw, Daniel L. Rosewater
Abstract: Disclosed are compounds of the formula: or the pharmaceutically acceptable addition salts thereof wherein: R1 is halogen or C1-C4 alkyl; and R2 and R3 are the same or different and represent hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, alkylthio, hydroxy, amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino, or R2 and R3 together represent a 4 carbon alkenylene moiety that together with the phenyl ring to which they are attached form a naphthyl moiety, which compounds are useful in the treatment of neuropsycological diseases such as schizophrenia, psychotic depression and mania.
Abstract: Arylpyrimidinone compounds that act as selective modulators of CRF 1 receptors are provided. These compounds are useful in the treatment of a number of CNS and periphereal disorders, particularly stress, anxiety, depression, cardiovascular disorders, and eating disorders. 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 CRF receptors and as standards in assays for CRF receptor binding. Methods of using the compounds in receptor localization studies are given.
Abstract: Melanin concentrating hormone receptor ligands (especially 1-benzyl-4-aryl-piperazines, 1-benzyl-4-aryl-piperidines and related compounds), capable of modulating MCH receptor activity, are provided. Such ligands may be used to modulate MCH binding to MCH receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of metabolic, feeding and sexual disorders in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for detecting MCH receptors (e.g., receptor localization studies).
Type:
Grant
Filed:
May 21, 2002
Date of Patent:
October 11, 2005
Assignee:
Neurogen Corporation
Inventors:
Alan Hutchison, Linda M. Gustavson, John M. Peterson, Dario Doller, Timothy M. Caldwell, Taeyoung Yoon, Wallace C. Pringle, Yiping Shen, Cheryl Steenstra
Abstract: The invention provides 4-imidazol-1-ylmethyl pyrimidine of the formula that bind to GABAA receptors. In the above formula, R1, R2 R3, R4, R5, R6 and Ar 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:
Grant
Filed:
November 6, 2003
Date of Patent:
October 4, 2005
Assignee:
Neurogen Corp.
Inventors:
Linghong Xie, Bingsong Han, Yuelian Xu, George D. Maynard