Neurogen Corporation

Pfizer Corporation

Novartis International Pharmaceutical, Ltd.

Linghong Xie

George D Maynard

Bingsong Han

Yang Gao

Yuelian Xu

Manuka Ghosh

Jun Yuan

George P Luke

Kevin S Currie

Scott A Mitchell

Bertrand Leo Chenard

John M Peterson

Kyungae Lee

Ping Ge

Stanislaw Rachwal

Lawrence Albert Vincent

Daniel Yohannes

Xiaojun Liu

Zhe-Quing Wang

Arthur Nagal

Joseph W Ochterski

Alan J Hutchison

Andrew Y Thurkauf

Pamela Ann Albaugh

Kenneth Shaw

He Zhao

Jiong Lan

Guiying Li

Timothy M Caldwell

Nian Liu

Wallace C Pringle

Vinod Kumar Singh

Robert Ohliger

Xiao Shu He

Suoming Zhang

LuYan Zhang

The invention provides packaged pharmaceutical preparations of Aryl substituted imidazoles, pyrazoles, pyridizines and related compounds of the Formula where the variables are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of the invention act bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in treating a variety of inflammatory and immune system disorders.

Aryl imidazoles and related compounds as C5a receptor modulators

Dipiperazinyl ketones and related analogues are provided, as are methods for their preparation and use. Such compounds may generally be used to modulate ligand binding to histamine H3 receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of disorders in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and therapeutic methods are provided, as are methods for using such ligands for detecting histamine H3 receptors (e.g., receptor localization studies).

Dipiperazinyl ketones and related analogues

Piperazinyl oxoalkyl tetrahydroisoquinolines and related analogues of the Formula: are provided, in which variables are as described herein. Such compounds may be used to modulate ligand binding to histamine H3 receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) and other 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 histamine H3 receptors (e.g., receptor localization studies).

Piperazinyl oxoalkyl tetrahydroisoquinolines and related analogues

Thiazole amides, imidazole amides and related analogues of the Formula: are provided, in which variables are as described herein. Such compounds may be used to modulate ligand binding to histamine H3 receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) and other 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 histamine H3 receptors (e.g., receptor localization studies).

Thiazole amides, imidazole amides and related analogues

The invention provides compounds of Formula (I) that bind to GABAreceptors. In the above formula, variables are defined herein. Such compounds may be used to modulate ligand binding to GABAreceptors 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 GABAreceptors (e.g., receptor localization studies) 

Aryl acid pyrimidinyl methyl amides, pyridazinyl methyl amides and related compounds

Disclosed are compounds of the formula and the pharmaceutically acceptable salts thereof wherein R, Ar, A, n, Rand Rare defined herein. These compounds are highly selective agonists, antagonists or inverse agonists for GABAbrain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAbrain 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 also disclosed.

Substituted fused pyrroleoximes and fused pyrazoleoximes

Compounds of Formula I are provided, as are methods for their preparation. The variables Z, Z, Z, R, R, R, R, Rand Ar in the above formula are defined herein. Such compounds may be used to modulate ligand binding to GABAreceptors 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 GABAreceptors (e.g., receptor localization studies).

Imidazo-pyrimidines and triazolo-pyrimidines: benzodiazepine receptor ligands

The invention provides imidazol-1-ylmethyl pyridazine derivatives of the formula: that bind to GABAreceptors. In the above formula, R, RR, R, R, Rand Ar are defined herein. Such compounds may be used to modulate ligand binding to GABAreceptors 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 GABAreceptors (e.g., receptor localization studies).

Imidazol-1-ylmethyl pyridazine derivatives

Substituted imidazolylmethyl pyridine and pyrazine derivatives that bind to GABAreceptors are provided. Such compounds may be used to modulate ligand binding to GABAreceptors 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 GABAreceptors (e.g., receptor localization studies).

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The invention provides 4-imidazol-1-ylmethyl pyrimidine of the formulathat bind to GABAreceptors. In the above formula, R, RR, R, R, Rand Ar are defined herein. Such compounds may be used to modulate ligand binding to GABAreceptors 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 GABAreceptors (e.g., receptor localization studies).

4-imidazol-1-ylmethyl-pyrimidine derivatives

Disclosed are heterocyclic compounds of the formulaand the pharmaceutically acceptable salts thereof wherein the variables A, V, Y, J, E, X, T, G, Q, W, Z, b, n and m are defined herein. These compounds are highly selective agonists, antagonists or inverse agonists for GABAbrain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAbrain receptor.

Heterocyclic compounds as ligands of the GABAA receptor

This invention relates to heteroaryl substituted fused bicyclic heteroaryl compounds, such as heteroaryl substituted imidazopyridines, imidazopyrazines, imidazopyridizines, imidazopyrimidines, and imidazothiazoles, which may be described by Formula I or Formula II: The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABAreceptors. 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. Processes for preparing compounds of Formula I and Formula II are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I or Formula II 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 GABAreceptors in tissue sections.

Heteroaryl substituted fused bicyclic heteroaryl compound as GABAA receptor ligands

Substituted fused pyrroleimines and pyrazoleimines

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Guilford, CT, United States of America

Linghong Xie