Glaxo Wellcome Inc.

Smithkline Beecham Corporation

Glaxosmithkline LLC

Glaxo Group Limited

Glaxo Wellcomeinc.

Timothy Mark Willson

Steven Anthony Kliewer

Jon Loren Collins

Milana Dezube

Curt Dale Haffner

Elizabeth Ellen Sugg

Patrick Reed Maloney

Jurgen M Lehmann

Jerzy Ryszard Szewczyk

Marcos Sznaidman

Millard Hurst Lambert, Iii

Ronald George Sherrill

Michael Lawrence Sierra

Jeffrey Alan Oplinger

Christopher Joseph Aquino

Huaqiang Eric Xu

Gavin Charles Hirst

Marcus Brackeen

Brad Richard Henke

Daniel David Sternbach

Stacey A Jones

Esther Yu-Hsuan Chao

Christopher P Holmes

Istvan Kaldor

Robert Anthony Mook

David Norman Deaton

Grady Evan Boswell

Eugene Lee Stewart

Matthew J Sharp

James Martin Lenhard

Sharon Davis Boggs

Peter W Jeffs

Julie Beth Stimmel

Adam Michael Fivush

John Mark O'Callaghan

Derek James Parks

Ludwig William Stuart

Zhengdong Wu

Jeffrey Edmond Cobb

Greg Alan Erickson

Traci Mansfield

Steven Gerard Blanchard

Tanya Momtahen

Edward Martin Suh

James Mood Chapman, Jr

Peter Jonathan Brown

The present invention relates to a novel human orphan nuclear receptor that binds to a cytochrome P-450 monooxygenase (CYP) promoter and that is activated by compounds that induce CYP gene expression. The invention further relates to nucleic acid sequences encoding such a receptor, to methods of making the receptor and to methods of using the receptor and nucleic acid sequences encoding same. The invention also relates to non-human animals transformed to express the human receptor and to methods of using such animals to screen compounds for drug interactions and toxicities.

Orphan nuclear receptor

The invention relates to methods for the treatment or prevention of an LXR mediated disease or condition, including cardiovascular disease and atherosclerosis, novel compounds of formula (I) for use in such methods and pharmaceutical compositions comprising compounds for use in such methods. 

Purine derivatives as liver X receptor agonists

Pregnane X receptor method

Methods for the treatment of cholestatic liver disease and reduction and prevention of hepatic injury resulting from cholestasis via administration of a FXR ligand are provided.

Compositions and methods for hepatoprotection and treatment of cholestasis

The present invention includes nuclear receptor heterodimer and nuclear receptor-coactivator peptide assays for identifying ligands for nuclear receptors, utilizing scintillation proximity and fluorescence resonance energy transfer (FRET), and methods of using identified ligands.

Use of FXR ligands

Activator of PPAR delta

Compounds of Formula (1) are disclosed. These compounds include selective activators of human PPAR delta.

Activators of PPAR delta

The present invention discloses novel PPAR gamma ligands of Formula (I) and pharmaceutically acceptable salts and solvates thereof. The present invention also discloses a method for treating osteoporosis by administration of a PPAR gamma antagonist.

Thiazole derivatives as PPAR gamma ligands

The present invention discloses compounds of formula (I), and tautomeric forms, pharmaceutically acceptable salts, or solvates thereof. Preferably, the compounds of the invention are dual activators of hPPAR&ggr; and hPPAR{acute over (&agr;)}.

Substituted oxazoles and thiazoles derivatives as hPPAR&ggr; and hPPAR&agr; activators

Novel compounds of Formula (1) and esters, salts, and physiologically functional derivatives thereof are disclosed. Methods for preparing and using the compounds are also disclosed. Many of these compounds are selective activators of PPAR alpha. The compounds are particularly useful for treating obesity.

Chemical compounds

A compound having formula (I), wherein A is selected from the group consisting of: (i) phenyl, wherein said phenyl is optionally substituted by one or more halogen atoms, C,alkyl, C,alkoxy, C,fluoroalkoxy, nitrile, or &mdash;NR,R,where R,and R,are independently hydrogen or C,alkyl; (ii) a 5- or 6-membered hetrocyclic group containing at least one heteroatom selected from oxygen, nitrogen and sulfur; and (iii) a fused bicyclic ring (a), wherein ring C represents a heterocyclic group as defined in point (ii) above, which bicyclic ring is attached to group B via a ring atom of ring C; B is selected from the group consisting of: (iv) C,alkylene; (v) &mdash;MC,alkylene or C,alkyleneMC,alkylene, wherein M is O, S, or &mdash;NR,wherein R,represents hydrogen or C,alkyl; (vi) a 5- or 6-membered heterocyclic group containing at least one nitrogen heteroatom and optionally at least one further heteroatom selected from oxygen, nitrogen and sulfur and optionally substituted by C,alkyl; and (vii) Het-C,alkylene, wherein Het represents a heterocyclic group as defined in point (vi) above; Alk represents C,alkylene; R,represents hydrogen or C,alkyl; Z is selected from the group consisting of: (viii) &mdash;(C,alkylene) phenyl, which phenyl is optionally substituted by one or more halogen atoms; and (ix) &mdash;NR,R,, wherein R,represents hydrogen or C,alkyl, and R,represents &mdash;Y&mdash;(C&boxH;O)&mdash;T&mdash;R,, or &mdash;Y&mdash;(CH(OH))&mdash;T&mdash;R,.

Substituted 4-hydroxy-phenylalcanoic acid derivatives with agonist activity to PPAR-gamma

Novel non-steroidal ligands for the estrogen receptor which possess tissue-dependent estrogenic and antiestrogenic activity as well as methods for making the same and their applications in treating a variety of disease states.

Non-steroidal ligands for the estrogen receptor

Oxoazepine derivatives

Use of agonists of the peroxisome proliferator activated receptor alpha

The present invention provides radiolabeled 5-{4-[2-(Methyl-pyridine-2-yl-amino)-ethoxy]-benzyl}-thiazolidine-2,4-dion e. In another aspect, the present invention provides a method for determining whether a compound does or does not interact directly with PPAR-gamma, comprising the step of specifically binding a radiolabeled compound of this invention to the ligand binding domain of PPAR-gamma.

Activators of the nuclear orphan receptor peroxisome

Growing community of inventors

Durham, NC, United States of America

Timothy Mark Willson