The Broad Institute, Inc.

Massachusetts Institute of Technology

The General Hospital Corporation

Wyeth

The General Hospital Corporation D/b/a Massachusetts General Hospital

Yan-Ling Zhang

Edward Holson

Florence Fevrier Wagner

Michel Weiwer

Stephen J Haggarty

Michael C Lewis

Li-Huei Tsai

Jennifer Q Pan

Michelle Palmer

Edward Scolnick

Qihong Xu

Bridget K Wagner

Tracey Lynn Petryshen

Luka Dordevic

Morten Lundh

Douglas Wilson

Bruce Follows

Jinbo Lee

Zhao-Kui Wan

Steve Yikkai Tam

Michael J Smith

Kenneth W Foreman

David V Erbe

Steven J Kirincich

Weixin Xu

Florence Fevrier

Jun-Jun Wu

Michael Lewis

Steven Haggarty

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.

Dopamine D2 receptor ligands

The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R, R, R, Rand t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.

Inhibitors of histone deacetylase

The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X, X, X, X, X, W, W, W, and Ware as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting &#x3b2;-cells and improving insulin resistance. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals.

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0-arrestin pathway and/or on the cAMP pathway.

The invention relates to a compound of Formula I:F&#x2014;X-L-X&#x2014;P&#x2014;X-G&#x2003;&#x2003;(Formula I).

Fluorescent substrates for determining lysine modifying enzyme activity

The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X, X, X, X, X, W, W, W, and Ware as described. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting &#x3b2;-cells and improving insulin resistance. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals. 

Protein tyrosine phosphatases (PTPases) such as PTP1B can play a role in regulating a wide variety of cellular responses such as insulin signaling. Substituted thiophene compounds such as, for example, 2-carboxyl, 3-carboxymethoxy, 5-aryl substituted thiophenes, can inhibit PTP1B and thereby induce greater insulin sensitivity. Accordingly, PTP1B inhibition can provide an alternate treatment for PTPase-mediated disorders such as diabetes.

Inhibitors of protein tyrosine phosphatase 1B

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Lexington, MA, United States of America

Yan-Ling Zhang