Neurogen Corporation

Other

The Cleveland Clinic Foundation

Pfizer Corporation

Guiying Li

Pamela Ann Albaugh

Alan J Hutchison

Manuka Ghosh

Jun Yuan

George D Maynard

Linda M Gustavson

John M Peterson

Kyungae Lee

Nian Liu

Kevin S Currie

Scott A Mitchell

Guolin Cai

George P Luke

Robert H Silverman

Paul F Torrence

Ling Hong Xie

Spiros Liras

Martin Patrick Allen

Vinod Kumar Singh

Wei Hao Xiao

Nick Mario Cirino

Bertrand Leo Chenard

Mark R Player

Linghong Xie

Dario Doller

Wallace C Pringle

James G Tarrant

John K Cowell

Seiji Kondo

Mary-Margaret E O'Donnell

Vinod Singh

Xie Ling Hong

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 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.

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

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 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

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.

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

The present invention relates to chimeric molecules comprising an oligonucleotide complementary to a region of the ribonucleotide component of telomerase attached to an activator of RNase L (&ldquo;activator-antisense complex&rdquo;) which specifically cleaves the ribonucleotide portion of a telomerase enzyme. The present invention relates to methods of inhibiting telomerase enzymatic activity with activator-antisense complexes targeted to the RNA component of telomerase. The present invention further relates to methods of treating malignant neoplastic disease, wherein the malignant cells contain a telomerase activity that is necessary for the growth of the malignant cells.

RNase L activators and antisense oligonucleotides effective to treat telomerase-expressing malignancies

The present invention relates to methods of inhibiting infection by RNA viruses with complexes of an activator of RNase L and an oligonucleotide that is capable of binding to the genome, antigenome or mRNAs of a negative strand RNA virus to specifically cleave the genomic or antigenomic RNA strand of the virus. In accordance with the present invention, the methods and complexes of the invention may be applied to target any negative strand RNA virus. The invention in one embodiment relates to a covalently linked complex of an oligonucleotide that is capable of binding to the genomic or antigenomic template RNA strand of a negative strand RNA virus and/or binding to an mRNA of a viral protein (an &ldquo;antisense oligonucleotide&rdquo;) coupled to an activator of RNase L. In a preferred embodiment of the present invention, the oligonucleotide component of the complex is complementary to a region of the viral genomic RNA strand characterized by repeated or consensus sequences.

RNase L activators and antisense oligonucleotides effective to treat RSV infections

The invention concerns a compounds and methods for treating infection with Respiratory Syncytial Virus. The compounds comprise an antisense portion, which is complementary to a normally single stranded portion of the RSV antigenomic strand (the mRNA strand), a linker and a oligonucleotide activator of RNase L, a ubiquitous non-specific RNase. The method comprised forming a complex of an activated RNase L and the antisense molecule. The application teaches methods of determining which portions of the RSV antigenomic strand are normally single-stranded. The application teaches that an antisense oligonucleotide having the sequence of residues 8281-8299 of the RSV genome is particularly useful to practice the invention and provides in vitro results superior to those obtainable with the conventional drug of choice, ribavirin.

RNase L activators and antisense oligonucleotides effective to treat RSV

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Branford, CT, United States of America

Guiying Li