Yale University

Glaxosmithkline Intellectual Property Development Limited

Cambridge Enterprise Limited University of Cambridge

William L Jorgensen

Richard J Bucala

Karen S Anderson

Pawel Dziedzic

Vinay Trivedi-Parmar

Jose Cisneros

Joseph Schlessinger

Andrew D Hamilton

Craig M Crews

Joelle Le

John David Harling

Denton Wade Hoyer

Sebastien Andre Campos

Ian Edward David Smith

Afjal Hussain Miah

Peter C Gareiss

Julien Michel

Anke G Roth

Dennis Buckley

Alessio Ciulli

Juliana Ruiz-Caro

Inge Van Molle

Jeffrey Gustafson

Hyun-Seop Tae

The compounds of Formula I described herein regulate activity of JAK2 by specifically binding to the JAK2 pseudokinase domain, JH2, and are useful as therapeutic agents in the treatment or amelioration of myeloproliferative disorders. Also provided herein are methods of treating myeloproliferative disorders, and methods of making compounds of Formula I.

Selective JAK2 pseudokinase ligands and methods of use

In one aspect, the invention comprises compounds that bind and inhibit macrophage migration inhibitory factor. In another aspect, the invention provides methods of treating, ameliorating, and/or preventing inflammatory disease, neurological disorders and cancer using the compounds of the invention.

Pyrazole-containing macrophage migration inhibitory factor inhibitors

The invention provides novel heterocyclic compounds, pharmaceutical compositions and methods of treatment that modulate levels of MIF expression and treat disorders associated with high or low levels of MIF expression.

MIF modulators

In one aspect, the invention comprises compounds that bind and inhibit macrophage migration inhibitory factor. In another aspect, the invention provides methods of treating inflammatory disease, neurological disorders and cancer using the compounds of the invention.

The present disclosure describes biaryl triazole compounds, as well as their compositions and methods of use. The compounds inhibit the activity of macrophage migration inhibitory factor and are useful for the treatment of diseases, e.g., inflammatory diseases and cancer.

Biaryltriazole inhibitors of macrophage migration inhibitory factor

The present invention provides novel inhibitors of MIF tautomerase activity. In certain embodiments, the compounds of the invention are useful in treating or preventing inflammatory and/or auto-immune diseases. In other embodiments, the compounds of the invention are useful in reversing, ameliorating, and/or preventing tumor growth. In yet other embodiments, the compounds of the invention are useful in reversing, ameliorating, and/or preventing angiogenesis.

Macrophage migration inhibitory factor inhibitors, and methods of making and using same

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and/or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an E3 ubiquitin ligase

The present invention includes novel compositions useful for preventing or treating an HIV-1 infection in a subject in need thereof. The present invention further includes a novel method of preventing or treating an HIV-1 infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of the invention. In one embodiment, the subject is further administered at least one additional therapeutic agent.

Compositions and methods of treating HIV-1 infections using same

The present invention is directed to novel catechol diether compounds, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV 1 and 2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.

Catechol diethers as potent anti-HIV agents

The present invention is directed to novel nanomolar and picomolar inhibitors of HIV reverse transcriptase, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV-1 and HIV-2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.

Compounds and methods for treating HIV infections

The present invention relates to compounds according to the formula I: Where Ris H or an optionally OH-substituted C-Calkyl; Ris OR, an optionally substituted Ccarbocyclic group which may be saturated or unsaturated (including aromatic) or an optionally substituted heterocyclic group; Ris an optionally substituted C-Chydrocarbyl group or an optionally substituted heterocyclic group; R, Rand Rare each independently H, an optionally substituted C-Calkyl group (preferably CH, CHCHor CF), halogen (preferably F, Cl, Br), OR, CN, NO, a C-Cthioether, a C-Cthioester group, an optionally substituted COR group, an optionally substituted COR group or an optionally substituted OCOR group (preferably Ris H); R is H or an optionally substituted C-Calkyl group; RHET is an optionally substituted heterocyclic group; and pharmaceutically acceptable salts, solvates or polymorphs thereof. 

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Deep River, CT, United States of America

William L Jorgensen