Wake Forest University

The United States of America, As Represented by the Secretary, Department of Health and Human Services

S Bruce King

Leslie B Poole

Jacquelyn S Fetrow

James B Mitchell

David A Wink

Mark Thomas Gladwin

Murali Krishna Cherukuri

Daniel B Kim-Shapiro

Freddie R Salsbury, Jr

Wilmarie Flores-Santana

Karin D Scarpinato

Daniel A Sweeney

Disclosed are nitroxide modified NSAID compounds of the formula (I) or a pharmaceutically acceptable salt or enantiomer thereof:  in which R, R, R, R, R, R, R, R, R, R, R, and n are defined herein and pharmaceutical compositions thereof. Further disclosed is a method of treating or preventing various disorders, such as inflammation, cancer, diabetes, a cardiovascular disorder, weight gain, polyps, and/or chronic pain, in a patient comprising administering an effective amount of a compound or pharmaceutically acceptable salt or enantiomer of formula (I). A method of imaging the compound or pharmaceutically acceptable salt or enantiomer of formula (I) in the body of the animal is also provided.

Nitroxide modified non-steroidal anti-inflammatory compounds and uses thereof in the treatment and prevention of diseases or disorders

Provided herein are methods of treating hemolysis by administering an active compound in an amount sufficient to treat said hemolysis. It has been found that nitroxyl donors or similar compounds preferentially react with cell-free OxyHb, as compared to OxyHb encapsulated in a red blood cell, and reacts with MetHb to form iron-nitrosyl Hb or nitrite bound MetHb. It has also been found that such compounds reduce cell-free Hb and hemolysis. Active compounds are also contemplated for use in combination therapies, for example, in combination with the administration of red blood cells and/or an agent that promotes hematopoiesis, or in combination with the administration of a nitric oxide donor.

Methods of treatment for hemolysis

The present invention provides compounds of Formula I: wherein: Ris a label (e.g., a detectable group and an anti-tumor agent); L is present or absent and when present is a linking group; and x represents an integer from 1 to 10; or a pharmaceutically acceptable salt thereof. The compounds are useful for, among other things, identifying cysteine sulfenic acids in proteins and monitoring oxidative damage in proteins and cells. Adduct formation can be detected using analytical methods such as electrospray ionization mass spectrometry and fluorescence.

Method for detecting compounds containing sulfenic acid using a 1,3-cyclohexanedione-based probe

Active compounds of Formula I are described: wherein: Rand Rare each independently C1-C4 alkyl; or Rand Rtogether form a C2-C7 alkylene chain; and Z is a non-steroidal anti-inflammatory drug (NSAID); along with pharmaceutically acceptable salts and prodrug thereof, and methods of using the same.

C-nitroso-derived nitroxyl donors

A method of treating cancer in a subject in need thereof comprises administering said subject reserpine, yohimbine, an analog thereof, or a pharmaceutically acceptable salt or prodrug thereof, in an amount effective to treat the cancer. Compounds and compositions useful for carrying out the method are also described.

Chemotherapeutic for inducing an MSH2-dependent apoptotic pathway

The present invention provides a method of synthesizing compounds of Formula I: wherein: Ris a label (e.g., a detectable groups; an anti-tumor agents); L is present or absent and when present is a linking group; and x represents an integer from 1 to 10; or a pharmaceutically acceptable salt thereof. the compounds are useful for, among other things, identifying cysteine sulfenic acids in proteins and monitoring oxidative damage in proteins and cells.

Method of synthesizing 1,3-cyclohexadione derived reagents useful for detection or isolation of sulfenic acid-containing compounds

The present invention provides compounds of Formula I: wherein: Ris a label (e.g., a detectable groups; an anti-tumor agent)s; L is present or absent and when present is a linking group; and x represents an integer from 1 to 10; or a pharmaceutically acceptable salt thereof. the compounds are useful for, among other things, identifying cysteine sulfenic acids in proteins and monitoring oxidative damage in proteins and cells.

Method for detecting target compounds containing sulfenic acids using new reagents

Active compounds of Formula (I) are described: wherein: Rand Rare each independently C1-C4 alkyl; or Rand Rtogether form a C2-C7 alkylene chain; and Z is a non-steroidal anti-inflammatory drug (NSAID); along with pharmaceutically acceptable salts and prodrug thereof, and methods of using the same.

The present invention provides compounds of Formula I: wherein: Ris a label (e.g., a detectable groups; an anti-tumor agent)s; L is present or absent and when present is a linking group; and x represents an integer from 1 to 10; or a pharmaceutically acceptable salt thereof. The compounds are useful for, among other things, identifying cysteine sulfenic acids in proteins and monitoring oxidative damage in proteins and cells.

Growing community of inventors

Walnut Cove, NC, United States of America

S Bruce King