Neurogen Corporation

Merrell Pharmaceuticals, Inc.

Novartis International Pharmaceutical, Ltd.

Hoechst Marion Roussel

Aventis Pharmaceuticals Inc.

Pfizer Corporation

Merrell Dow Pharmaceuticals

Other

Novartis Ag

George D Maynard

Jun Yuan

Alan J Hutchison

John M Kane

Elizabeth M Kudlacz

Timothy Paul Burkholder

Linghong Xie

Manuka Ghosh

Kyungae Lee

Albert A Carr

Kevin S Currie

Hsien C Cheng

Mark W Dudley

Scott A Mitchell

Stanislaw Rachwal

Nian Liu

He Zhao

George P Luke

Qin Guo

Bingsong Han

Pamela Ann Albaugh

Bertrand Leo Chenard

Linda M Gustavson

Raymond F Horvath

John M Peterson

James William Darrow

Braulio Santiago

Andrew Y Thurkauf

Kenneth Shaw

Christopher R Dalton

Guiying Li

Tieu-Binh Le

Peter Hrnciar

Guolin Cai

Xiao-shu He

Yang Gao

Larry D Bratton

Yuelian Xu

Daniel Yohannes

Xiaojun Liu

Ling Hong Xie

Robert W DeSimone

Kevin J Hodgetts

Spiros Liras

James E Krause

Martin Patrick Allen

Xiaoyan Zhang

Robbin M Brodbeck

Zihong Guo

Lawrence Albert Vincent

Vinod Kumar Singh

Arthur Nagal

Zhe-Quing Wang

Richard Lew

Christopher John O'Donnell

Taeyoung Yoon

Jennifer N Tran

Stephane De Lombaert

Harry Brielmann

Suoming Zhang

Xiao Shu He

LuYan Zhang

Tieu-Bihn Le

Larry Don Bratton

John D Kane

Vinod Singh

Xie Ling Hong

Pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds analogues of the formula: wherein R, R, R, E, Z, Z, Z, and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds of the invention bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds, which are useful as probes for the localization of C5a receptors.

Pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds

The present invention provides compounds of Formula (I) or (II) salt form or prodrug thereof, wherein variables are defined herein, that are modulators of metalloproteases such as matrix metalloproteases (MMPs) and ADAMs. The compounds or compositions described herein can be used to treat diseases associated with metalloprotease activity including, for example, arthritis, cancer, cardiovascular disorders, skin disorders, inflammation or allergic conditions. 

3-aryl-5,6-disubstituted pyridazines

4,5-disubstituted-2-arypyrimidines of Formula I and Formula II are provided: wherein R, R, R, R, R, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula I and II bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 4,5-disubstituted-2-arylpyrimidines, which are useful as probes for the localization of C5a receptors.

4,5-disubstituted-2-aryl pyrimidines

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

1-aryl-4-substituted isoquinoline or 1-aryl-3,4-disubstituted isoquinoline analogues of Formula I and Formula II, as follows: wherein R, R, R, R, R, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula I and II bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 1-aryl-4-substituted isoquinolines or 1-aryl-3,4-disubstituted isoquinolines, which are useful as probes for the localization of C5a receptors.

1-aryl-4-substituted isoquinolines

3-substituted-6-aryl pyridines of Formula I are provided: wherein R, R, R, R, R, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula I bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 3-substituted-6-aryl pyridines, which are useful as probes for the localization of C5a receptors.

3-substituted-6-aryl pyridines

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 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. 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 GABAreceptors in tissue sections.

Benzimidazole and pyridylimidazole derivatives

4,5-disubstituted-2-arylpyrimidines of Formula I and Formula II are provided: wherein R, R, R, R, R, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula I and II bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 4,5-disubstituted-2-arylpyrimidines, which are useful as probes for the localization of C5a receptors.

3-substituted-6-aryl pyridines of Formula I are provided: wherein R, R, R, R, R, A and Ar are defined herein. Such compounds are ligands of C5a receptor. Preferred compounds of Formula I bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 3-substituted-6-aryl pyridines, which are useful as probes for the localization of C5a receptors.

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 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. 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 GABAreceptors in tissue sections.

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 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 receptos. 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.

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

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Clinton, CT, United States of America

George D Maynard