Smithkline Beecham Corporation

Glaxosmithkline Intellectual Property Development Limited

Yale University

Glaxo Group Limited

Smithkline Beechum P.l.c.

Cambridge Enterprise Limited University of Cambridge

John David Harling

Mervyn Thompson

Barry S Orlek

Ian Edward David Smith

Afjal Hussain Miah

Sebastien Andre Campos

Frank Peter Harrington

Linda N Casillas

Savvas Kleanthous

Mark David Rackham

Ian Edward Smith

Thomas H Brown

Laramie Mary Gaster

Michael S Hadley

Craig M Crews

Alan D Borthwick

Paul John Beswick

Dennis Buckley

Joelle Le

Vipulkumar Kantibhai Patel

Robert William Ward

Nigel Stephen Watson

William L Jorgensen

Robert John Young

Millard Hurst Lambert, Iii

Jag Paul Heer

Denton Wade Hoyer

Juliet Kay Simpson

Julien Michel

Peter C Gareiss

Hyun-Seop Tae

Anke G Roth

Alessio Ciulli

Inge Van Molle

Wendy Rebecca Irving

Jeffrey Gustafson

Dentin Wade Hoyer

Craig Crews

William Jorgensen

The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.

Conjugates comprising RIPK2 inhibitors

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

Compounds

1AP E3 ligase directed proteolysis targeting chimeric molecules

A compound of formula (I): or a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.

Benzothiophene derivatives as estrogen receptor inhibitors

The invention relates to compounds of formula (I): wherein substituents are as defined.

3-sulfonylamino-pyrrolidine-2-one derivatives as inhibitors of factor Xa

A compound of formula (I) or a pharmaceutically acceptable salt, solvate, or hydrolysable ester thereof, Wherein:

Chemical compounds

The invention relates to novel isoquinolines and their use as anticonvulsants and in the treatment of a variety of disorders.

Compounds of formula (I) or a pharmaceutically acceptable salt thereof:

Triarylimidazole derivatives as cytokine inhibitors

The invention relates to novel isoquinolines and their use as anticonvulsant and in the treatment of a variety of disorders.

Tetrahydronaphthyridinyl-carboxamides having anti-convulsant activity

This invention relates to novel substituted isoquinoline derivatives and their use as anticonvulsants.

Substituted isoquinoline derivatives and their use as anticonvulsivants

Substituted isoquinoline derivatives and their use as inticonvulsants

Compounds of formula (I) and pharmaceutically acceptable salts and solvates: where R is hydrogen, C alkyl (optionally substituted by hydroxy or C alkoxy), phenyl-C alkyl-, C alkenyl, C alkynyl; R is hydrogen or, up to three substituents selected from halogen, NO , CN, N , CF O&mdash;, CF S&mdash;, CF SO &mdash;, CF CO&mdash;, C alkyl, C alkenyl, C alkynyl, C perfluoroalkyl, C cycloalkyl, C cycloalkyl-C alkyl-, C alkyl, C alkylCO&mdash;, C cycloalkylO&mdash;, C cycloalkylCO&mdash;, C cycloalkyl-C alkylO&mdash;, C cycloalkyl-C alkylCO&mdash;, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C alkyl-, C alkylS&mdash;, C alkylSO &mdash;, (C alkyl) NSO &mdash;, (C alkyl)NHSO &mdash;, (C alkyl) NCO&mdash;, (C alkyl)NHCO&mdash; or CONH ; or &mdash;NR R where R is hydrogen or C alkyl, and R is hydrogen, C alkyl, formyl, &mdash;CO C alkyl or &mdash;COC alkyl; or two R groups together form a carbocyclic ring that is saturated or unsaturated, optionally interrupted by O or NH; R groups and R groups are each independently hydrogen or C alkyl and/or the two R groups and/or the two R groups together form a C spiroalkyl group, provided that at least one R or R group is not hydrogen; and X is selected from hydrogen, halogen, cyano, alkyl and alkoxy, are useful in the treatment and prophylaxis of epilepsy, migraine, and other disorders.

Growing community of inventors

Stevenage, United Kingdom

John David Harling