Genzyme Corporation

Bradford Hirth

Craig S Siegel

John L Kane, Jr

Shuang Qiao

John M Williams

Scott F Sneddon

Sharon R Nahill

Elina Makino

Hans-Peter Biemann

Elyse Bourque

Fred Vinick

Yibin Xiang

Cassandra Celatka

John P Leonard

Mary A Cromwell

Seng H Cheng

Andrew Charles Good

John Marshall

Ronald K Scheule

Markus Metz

Zhong Zhao

Frederic Vinick

Thomas A Natoli

James W Lillie

Hanlan Liu

Bing Wang

Oxana Beskrovnaya

Paul Mason

Herve Husson

Thomas O'Shea

Mario A Cabrera-Salazar

Katherine Jancsics

Renato Sklerj

Fazeela Morshed

Lingyun Li

Renato Skerlj

Michael R Angelastro

Sukanthini Thurairatnam

Kwon Yon Musick

Lisa M Cuff

Renato Tony Skerlj

Sungtaek Lim

Robert H Barker, Jr

Jill Gregory

Andrew Janjigian

Yong-Mi Choi

James Pribish

John Jiang

Marko J Pregel

John Leonard

Sachin Maniar

Mark Munson

Katherine Jancisics

Ronald Scheule

Mario Cabrera-Salazar

Andrew Good

Thomas Natoli

The invention relates to inhibitors of glucosylceramide synthase (GCS) of the Formula I: represented by the following structural formula or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein, useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer.

Glucosylceramide synthase inhibitors

Described herein is a compound of Formula (I), and pharmaceutically acceptable salts thereof. Also described herein are compositions and the use of such compositions in methods of treating a variety of diseases and conditions, in particular Krabbe's Disease (KD) and Metachromatic leukodystrophy (MLD).

UDP glycosyltransferase inhibitors and methods of use

The invention relates to inhibitors of glucosylceramide synthase (GCS), such as Compound of Formula I, shown below, as defined herein, useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer. 

The present invention provides compounds which are modulators of TNF-&#x3b1; signaling and methods of use thereof for treating a patient having a TNF-&#x3b1; mediated condition. The compounds can be represented by the following structural formulas: 

Modulators of TNF-&#x3b1; signaling

Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.

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The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.

Novel mechanism-based inhibitors of S-adenosyl-L-methionine decarboxylase are provided. These compounds of formula (1) inhibit the life cycle of trypanosomes, and are useful to treat subjects infected with African trypanosomes. The invention includes pharmaceutical compositions and methods of using the compounds of formula (1).

Inhibitors of S-adenosyl-L-methionine decarboxylase

Modulators of TNF-&#x3b1;signaling

Tetrahydroisoquinoline derivatives, pharmaceutical compositions comprising them and methods of treating disease are disclosed herein. The disclosed compounds are useful in the treatment and prevention of diseases mediated by chloride channel activity and/or protein trafficking, including, but not limited to, diseases associated with impaired mucociliary clearance such as cystic fibrosis, bronchitis, emphysema, and the like.

Tetrahydroisoquinoline derivatives for treating protein trafficking diseases

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Littleton, MA, United States of America

Bradford Hirth