Harvard College

Organix, Inc.

Other

The General Hospital Corporation

University of Washington

Northeastern University

Beth Israel Deaconess Medical Center, Inc.

Fred Hutchinson Cancer Center

The Beth Israel Hospital Association

Hydra Biosciences, Inc.

The United States Government As Represented by the Department of Veterans Affairs

Oregon Health & Science University

Key Pharmaceuticals, Inc.

Massachusetts Institute of Technology

Fred Hutchinson Cancer Research Center

Peter C Meltzer

Bertha K Madras

Paul Blundell

Raj Kumar Razdan

Howard Paul Sard

Richard J Sharpe

Kenneth A Arndt

Zhengming Chen

Jayhong A Chong

Alan J Fischman

Glenn R Larsen

Christopher Fanger

Dennis John Underwood

Amy Ripka

Magdalene M Moran

Manfred Weigele

Xiaoguang Zhen

Stephen J Galli

Anu Mahadevan

William C Lumma

David R Elmaleh

Graham Johnson

Robert N Hanson

Alun G Jones

Julian Simon

Edwin W Rubel

David W Raible

Ashfaq Mahmood

Mario D Gonzalez

Weishi Miao

Pinglang Wang

Alan L Davison

Aaron Janowsky

Stephen L Galli

Jotham W Coe

Shanghao Liu

Bertha C Madras

Alan Davison

Alan G Jones

Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

Compounds and methods for preventing or treating sensory hair cell death

Disclosed herein are compounds that bind to the vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions comprising those compounds, and methods of treatment using said compounds and pharmaceutical compositions.

VMAT inhibitory compounds

The present application relates to compounds and methods for treating pain and other conditions related to TRPV3.

Compounds for modulating TRPV3 function

The present application relates to compounds of Formula I as defined herein, and methods for treating pain and other conditions related to TRPV3.

Substituted pyrimido 4.5-d pyrimidin-4-one compounds for modulating TRPV3 function

A method of diagnosing attention deficient-hyperactivity disorder (ADHD) in a human patient by assessing the level of dopamine transporter in at least one region of the patient's central nervous system, where an elevated level of dopamine transporter in the patient is indicative of ADHD. In embodiments of the invention, assessment of dopamine transporter levels includes assessing binding of a dopamine transporter ligand to the dopamine transporters using PET or SPECT.

Methods for diagnosing and monitoring treatment ADHD by assessing the dopamine transporter level

The present invention provides novel tropane compounds and methods for their use.

Tropane compounds

This invention to antagonists that inhibit transporters and receptors. The invention also relates to partial inhibitors of transporters and receptors that allow partial transport or partial binding of a compound to the transporter or receptor. The invention also relates to compounds that differentially prevent transport or binding through a transporter or to a receptor. The invention also relates to the use of these compounds for treating certain diseases and disorders.

Therapeutic compounds

New tropane analogs that bind to monoamine transporters are described, particularly, 8-aza, 8carbo and 8-oxo tropanes having 6- or 7-hydroxyl or ketone substituents. The compounds of the present invention can be racemic, pure R-enantiomers, or pure S-enantiomers. Certain preferred compounds of the present invention have a high selectivity for the DAT versus the SERT. Also described are pharmaceutical therapeutic compositions comprising the compounds formulated in a pharmaceutically acceptable carrier and a method for inhibiting 5-hydroxy-tryptamine reuptake of a monoamine transporter by contacting the monoamine transporter with a 5-hydroxytryptamine reuptake inhibiting amount of a compound of the present invention. Preferred monoamine transporters for the practice of the present invention include the dopamine transporter, the serotonin transporter and the norepinephrine transporter.

Tropane analogs and methods for inhibition of monoamine transport

Radiopharmaceutical compounds are disclosed. A tropane compound is linked through the N atom at the 8-position to a chelating ligand capable of complexing technetium or rhenium to produce a neutral labeled complex that selectively binds to the dopamine transporter over the serotonin transporter with a ratio of 10 or more. These compounds can be prepared as separate diastereoisomers as well as a mixture of diastereoisomers. Also disclosed are radiopharmaceutical kits for preparing the labeled radiopharmaceutical compounds.

Boat tropanes

Featured compounds have high monoamine transport affinity and are characterized by one of the following two general formulas set out above. The compounds bind selectively or non-selectively to monoamine transporters. The compounds are useful to treat various medical indications including attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke, and narcolepsy.

Compounds with high monoamine transporter affinity

The present invention relates to the therapeutic use of non-amine tropane analogues that bind to the SERT to treat neuropsychiatric disorders.

Serotonin transport inhibitors

New tropane analogs that bind to monoamine transporters are described, particularly, 8-aza, 8carbo and 8-oxo tropanes having 6- or 7-substituents. The compounds of the present invention can be racemic, pure R-enantiomers, or pure S-enantiomers. Certain preferred compounds of the present invention have a high selectivity for the DAT versus the SERT. Also described are pharmaceutical therapeutic compositions comprising the compounds formulated in a pharmaceutically acceptable carrier and a method for inhibiting 5-hydroxy-tryptamine reuptake of a monoamine transporter by contacting the monoamine transporter with a 5-hydroxytryptamine reuptake inhibiting amount of a compound of the present invention. Preferred monoamine transporters for the practice of the present invention include the dopamine transporter, the serotonin transporter and the norepinephrine transporter.

Growing community of inventors

Lexington, MA, United States of America

Peter C Meltzer