Neurogen Corporation

Pfizer Corporation

John M Peterson

Alan J Hutchison

Andrew Y Thurkauf

Jun Yuan

Raymond F Horvath

George D Maynard

Charles A Blum

Robert W DeSimone

Linda M Gustavson

Wallace C Pringle

Dario Doller

Guiying Li

Pamela Ann Albaugh

Xiao-shu He

Timothy M Caldwell

Yiping Shen

Cheryl K Steenstra

Taeyoung Yoon

Yang Gao

Linghong Xie

James E Krause

Xiaoyan Zhang

Helen Yin

Joseph W Ochterski

Richard Lew

Bingsong Han

Kevin S Currie

Scott A Mitchell

Kenneth Shaw

He Zhao

Guolin Cai

Kyungae Lee

Manuka Ghosh

Ping Ge

Robbin M Brodbeck

Bertrand Leo Chenard

Rajagopal Bakthavatchalam

Jiong Lan

George P Luke

Kevin J Hodgetts

Spiros Liras

Yuelian Xu

Harry Brielmann

Martin Patrick Allen

Nian Liu

James G Tarrant

Robert Ohliger

Ling Hong Xie

Vinod Kumar Singh

Mary-Margaret E O'Donnell

Christopher Mach

Vinod Singh

Xie Ling Hong

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

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

Compounds of Formula I are provided, in which variables are as described herein:  Such compounds 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).

Substituted 1-benzyl-4-substituted piperazine analogues

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).

Melanin concentrating hormone receptor ligands: substituted 1-benzyl-4-aryl piperazine analogues

Melanin concentrating hormone receptor ligands (especially substituted 2-(4-benzyl-piperazin-1-ylmethyl)-1H-benzoimidazole analogues), 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).

Melanin concentrating hormone receptor ligands: substituted 2-(4-benzyl-piperazin-1-ylmethyl)- and 2-(4-benzyl-diazepan-1-ylmethyl)-1H-benzoimidazole analogues

Disclosed are compounds of the formulaand the pharmaceutically acceptable salts thereof where the variables R, R, A, R, R, R, R', n, and W are defined herein. These compounds bind to the benzodiazepine site of GABAreceptors are provided and, therefore can 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.

(Oxo-pyrazolo[1,5a]pyrimidin-2-yl)alkyl-carboxamides

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

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.

High affinity small molecule C5a receptor modulators

Certain 4-aminomethyl-2-substituted imidazole derivatives and 2-aminomethyl-4-substituted imidazole derivatives; new classes of dopamine receptor subtype specific ligands

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, preferably human C5a receptors, Preferred compounds of the invention possess one or more, and preferably two or more, three or more, four or more, or all of the following properties in that they are; 1) multi-aryl in structure (having a plurality of un-fused or fused aryl groups), 2) heteroaryl in structure, 3) orally available in vivo (such that a sub-lethal or preferably a pharmaceutically acceptable oral dose can provide a detectable in vitro effect such as a reduction of C5a-induced neutropenia), 4) comprised of fewer than four, preferably fewer than three, or fewer than two, or no amide bonds, and 5) capable of inhibiting leukocyte chemotaxis at nanomolar concentrations and preferably at sub-nanomolar concentrations. Specifically exemplified representative compounds include, but are not limited to optionally substituted arylimidazoles, optionally substituted arylpyridyls, optionally substituted aryl-substituted cycloalkylimidazoles, optionally substituted arylpyrazoles, optionally substituted benzimidazoles, optionally substituted aryl-substituted tetrahydroisoquinolines, and optionally substituted biaryl carboxamides. 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. Additionally, this invention relates to the use such compounds as probes for the localization of C5a receptors.

(Oxo-pyrazolo&lsqb;1,5a&rsqb;pyrimidin-2-yl) alkyl-carboxamides

Imidazopyridines and related derivatives as selective modulators of bradykinin B2 receptors

Aryl and hetroaryl fused aminoalkyl-imidazole derivatives: selective modulators of bradykinin B2 receptors

Growing community of inventors

Durham, CT, United States of America

John M Peterson