Smithkline Beecham Corporation

Millard Hurst Lambert, Iii

Rodolfo Cadilla

Michael Lawrence Sierra

Daniel David Sternbach

Marcos Sznaidman

Huaqiang Eric Xu

Timothy Mark Willson

Stephen William Rafferty

Romain Luc Marie Gosmini

Curt Dale Haffner

Patrick Reed Maloney

Brad Richard Henke

Esther Yu-Hsuan Chao

Paul John Beswick

Vipulkumar Kantibhai Patel

John David Harling

Philip Stewart Turnbull

Amy Tsai Lu

Barry George Shearer

Paul Kenneth Spearing

Savvas Kleanthous

Juliet Kay Simpson

Guangcheng Kevin Liu

Jennifer Susan Smith

Christopher J Apolito

Randy K Bledsoe

David D McKee

Valerie Gail Montana

Kenneth H Pearce

Pierette Banker

Thomas B Stanley

Christopher J Delves

Ronnie Lee Hale

Michael Vance Milburn

Jeffrey Edmond Cobb

The present invention provides a compound of formula (I): 

Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors

The present invention provides combinations of compounds of formula (I) and other therapeutic agents for the treatment of PPAR related diseases. 

Thiazole derivatives for treating PPAR related disorders

Compounds of formula (1) or a pharmaceutically acceptable salt, solvate, acid isostere, or hydrolyzable ester thereof, are disclosed. Methods of making and using the compounds are also disclosed. In particular methods for treating diseases or conditions associated with one or more of human PPAR alpha, gamma, or delta ('hPPARs') comprising administration of a therapeutically effective amount of a compound of formula (1), are disclosed 

hPPARs activators

A method of modifying a test nuclear receptor (NR) polypeptide is disclosed. The method provides a test NR polypeptide sequence having a characteristic that is targeted for modification; aligning the test NR polypeptide sequence with at least one reference NR polypeptide sequence for which an X-ray structure is available; building a three-dimensional model for the test NR polypeptide using the three-dimensional coordinates of the X-ray structure(s) of at least one reference polypeptide and its sequence alignment with the test NR polypeptide sequence; examining the three-dimensional model of the test NR polypeptide sequence for characteristic differences with the reference polypeptide; and mutating at least one amino acid residue in the test NR polypeptide sequence at a characteristic difference, whereby the test NR polypeptide is modified.

Crystallized glucocorticoid receptor ligand binding domain polypeptide and screening methods employing same

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

Chemical compounds

The present invention provides compounds of formula (I). These compounds are used for the treatment of PPAR related diseases

Triazine derivatives of formula (I), which exhibit pharmacological activity at estrogen receptors alpha (ER alpha) and beta (ER beta) are described herein. The described invention also includes compositions and medicaments containing the triazine derivatives as well as processes for the preparation and use of such compounds, compositions and medicaments.

Piperazinyltriazines as estrogen receptor modulators

Activator of PPAR delta

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

Activators of PPAR delta

A method is disclosed for rational design of a PPAR, FXR, LXR-alpha, or LXR-beta antagonist comprising chemical modification of a PPAR, FXR, LXR-alpha, or LXR-beta agonist to: a) prevent formation of a hydrogen bond between the agonist and tyrosine or histidine, or tryptophan involved in receptor activation; and/or b) displace the tyrosine or histidine, or tryptophan involved in receptor activation from its agonist bound position. Preferably, little or no additional changes are made in the structure of the agonist so that the resulting antagonist is a close structural analogue of the agonist. Specific examples of PPAR gamma antagonists designed and prepared using the method of this invention are compounds of Formula (I) or (II), or pharmaceutically acceptable salts or solvates thereof, where in Formula (I) X is O, S, or NH; and R is methyl, ethyl, n-propyl, i-propyl, cyclopropyl, n-butyl, phenyl, or &mdash;CH OCH and wherein in Formula (II) X is C or N; and R is methyl, ethyl, n-propyl, i-propyl, &mdash;CH OCH , or &mdash;CO CH .

Oxazole PPAR antagonist

Growing community of inventors

Durham, NC, United States of America

Millard Hurst Lambert, Iii