Ardelyx, Inc.

Kosan Biosciences Incorporated

Pfizer Corporation

Bristol-Myers Squibb Compnay

Christopher Carreras

Jeffrey William Jacobs

Dominique Charmot

Michael Robert Leadbetter

Noah Bell

Marc Navre

Jason Gustaf Lewis

Eric Labonte

Tao Chen

Han-Ting Chang

Nicholas Reich

Yaoquan Liu

Daniel V Santi

Mark A Burlingame

Gary W Ashley

David C Myles

Brian Walter Metcalf

Robert G McDaniel

Yandong Li

Dean R Dragoli

Hong Fu

Matthew John Siegel

Yue Chen

Irina Dotsenko

Andrew King

Ingrid Langsetmo

Simon James Shaw

Yong Li

Jeffrey Jacobs

Susan Dillon

Eduardo J Rodriguez

Hao Zheng

Ying He

Xunxiang Du

Johan Oslob

Jason Lewis

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. The methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein. More particularly, the method comprises administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that inhibits NHE-3, -2 and/or -8 mediated antiport of sodium and/or hydrogen ions in the GI tract and is designed to be substantially impermeable to the layer of epithelial cells, or more specifically the epithelium of the GI tract. As a result of the compound being substantially impermeable, it is not absorbed and is thus essentially systemically non-bioavailable, so as to limit the exposure of other internal organs (e.g., liver, heart, brain, etc.) thereto. The present disclosure is still further directed to a method wherein a mammal is administered such a compound with a fluid-absorbing polymer, such that the combination acts as described above and further provides the ability to sequester fluid and/or salt present in the GI tract.

Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders

Provided are non-NHE3-binding agents having activity as phosphate transport/uptake inhibitors in the gastrointestinal tract, including in the small intestine, methods for their use as therapeutic or prophylactic agents, and related methods of drug discovery.

Compounds and methods for inhibiting phosphate transport

Provided are NHE3-binding and/or NHE3-modulating agents having activity as phosphate transport inhibitors, including inhibitors of phosphate transport in the gastrointestinal tract and the kidneys, and methods for their use as therapeutic or prophylactic agent.

NHE3-binding compounds and methods for inhibiting phosphate transport

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

The present disclosure is directed to compounds of the structure (X):CoreL-NHE)&#x2003;&#x2003;(X)wherein: wherein: wherein:

Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorder

Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein X, Y, A, Rand Rare as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein X, Y and A are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein X, Y, Rand Rare as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

The present disclosure is directed to compounds and methods for treating irritable bowel syndrome, chronic kidney disease and end stage renal disease by administering to a subject in need thereof a compound or a pharmaceutically acceptable salt thereof, wherein the compound has the structure 

The present disclosure is directed to compounds of the structure (X): wherein: wherein: wherein:

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Belmont, CA, United States of America

Christopher Carreras