Merck Sharp + Dohme Corp.

Merck + Co., Inc.

Lieber Institute, Inc.

The Johns Hopkins University

Lieber Institute for Brain Development

Sunesis Pharmaceuticals, Inc.

Merk & Co., Inc.

Lieber Institute Inc. Dba Lieber Institute for Brain Development

James C Barrow

Harold G Selnick

Philippe G Nantermet

Yifang Huang

Glen E Ernst

Scott E Wolkenberg

Michael Steven Poslusney

Scott T Harrison

Craig Alan Coburn

Shaun R Stauffer

Zhi-Qiang Yang

Nathan R Kett

Pankaj Jay Pasricha

Peter J Manley

Zhijian Zhao

Kenneth E Rittle

Shawn J Stachel

B Wesley Trotter

Philip E Sanderson

Thomas S Reger

Donnette D Staas

James J Mulhearn

Kausik K Nanda

William D Shipe

Hemaka Anthony Rajapakse

Joseph P Vacca

Matthew G Stanton

Bruce D Dorsey

Christopher D Cox

Peter D Williams

Terry A Lyle

Richard C Isaacs

Thomas M Connolly

Craig William Lindsley

John Howard Hutchinson

Roger M Freidinger

Linghang Zhuang

Mark T Bilodeau

Paul J Coleman

Melissa S Egbertson

Wenjin Yang

Steven D Young

Christopher S Burgey

Dominique Swinnen

Michael J Breslin

Lou Anne Neilson

Lekhanh O Tran

Catherine M Wiscount

Zhiqiang Yang

Amy Zartman

Georgia B McGaughey

Daniel Weinberger

Jeffrey Melamed

Ingrid Price Buchler

Kenneth J Stauffer

Jeffrey W Schubert

Kelly-Ann S Schlegel

ZhiQiang Yang

Phung L Ngo

Keith P Moore

Melody McWherter

Yiwei Li

David L Williams

John C Hartnett

Youheng Shu

Jennifer R Davis

Matthew M Morrissette

Eric Hostetler

Mary Beth Young

Andrew M Stern

Marikki Laiho

David Wisnoski

Wanli Lu

Bruce Fahr

Wesley B Trotter

Kellie Cutrona

Kyle A Robinson

Rowena V Cube

Phung Le Ngo

Florian Montel

Sabine Defays

Pablo De León

Kristen L Glass

Mark B Nolt

Philippe G Nanterment

Zhijan Zhao

Ingrid Buchler

Yoheng Shu

Laureen Colis

Cyrille Sur

Sara Sanders

Mattahew G Stanton

Phung Le Bondiskey

Glen Ernst

Pablo De LÉON

Sarah Sanders

Michael S Poslusney

Pyridine carboxamide compounds for inhibiting NaV1.8 and methods for treating a condition, disease, or disorder associated with an increased NaV1.8 activity or expression are disclosed.

Pyridine carboxamide compounds for inhibiting NAV1.8

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof, or an N-oxide thereof) of formula (I), which are positive allosteric modulators of one or more GABA-A receptors, e.g., which are peripherally restricted, positive allosteric modulators of one or more GABA-A receptors; e.g., which are positive allosteric modulators of one or more GABA-A receptors and which selectively target the peripheral nervous system and organs of the body, and which do not substantially pass through the blood-brain barrier. Said compounds are useful e.g., for the treatment of systemic diseases of the body, e.g., diseases in which modulation of one or more peripherally restricted GABA-A receptors is beneficial (e.g., diseases or disorders which are mediated by GABA-A neuronal activity. This disclosure also features pharmaceutical compositions containing the chemical entities described herein as well as methods of using same for the treatment of systemic diseases of the body.

Substituted benzopyrazolo[1,5-a][1,4]diazepines as GABA positive allosteric modulators

Pyridazine compounds for inhibiting NaV1.8 and methods for treating a condition, disease, or disorder associated with an increased NaV1.8 activity or expression are disclosed.

Pyridazine compounds for inhibiting Nav1.8

The present invention provides compounds and compositions which are positive allosteric modulators of GABA-A receptors that selectively target the peripheral nervous system and organs of the body, and which do not pass through the blood-brain barrier. The compounds and compositions of the present invention are useful for treatment of diseases or disorders which are mediated by GABA-A neuronal activity, such as, for example, visceral pain, gut motility, irritable bowel syndrome, functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance.

Peripherally restricted GABA positive allosteric modulators for the treatment of irritable bowel syndrome and other ailments of the peripheral nervous system

RNA polymerase I (Pol I) is a dedicated polymerase for the transcription of the 47S ribosomal RNA precursor subsequently processed into the mature 5.8S, 18S and 28S ribosomal RNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. Based on the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides were synthesized as inhibitors of Pol I and activators of the destruction of RPA194, the Pol I large catalytic subunit protein. The present invention identifies a set of bioactive compounds, including purified stereoisomers, that potently cause RPA194 degradation that function in a tightly constrained chemical space. Pharmaceutical compositions comprising these compounds and their uses in cancer and other Pol I related diseases is also provided.

Compounds which inhibit RNA polymerase, compositions including such compounds, and their use

Compounds that inhibit COMT enzyme and pharmaceutical compositions comprising the same are provided herein. Methods of treating various psychiatric and neurological disorders with the compounds and pharmaceutical compositions described herein are also provided.

COMT inhibiting methods and compositions

The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia. 

The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved.

Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders

The present invention is directed to triazolopyridinone compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

Triazolopyridinone PDE10 inhibitors

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Harleysville, PA, United States of America

James C Barrow