Janssen Pharmaceutica Nv

Johnson & Johnson Pharmaceutical Research & Development, LLC

Dionisios Rentzeperis

Frank A Lewandowski

Cynthia M Milligan

Marta Cristina Abad

Michael Gaul

Lily Lee Searle

Ludmila A Barnakova

Gilles C Bignan

Alexander Y Kim

John O'Neill

Hossein B Askari

The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

Substituted phenoxy N-alkylated thiazolidinediones as estrogen related receptor-&#x3b1; modulators

The crystal structure of the ligand binding domain of ERR-&#x3b1; in complex with a ligand that forms a reversible thioether bond to Cys325 of ERR-&#x3b1;, methods to measure dissociation rates for ligands that form reversible covalent bonds, and methods to design ligands that form reversible covalent bonds for use as modulators of ERR-&#x3b1; activity are disclosed. The crystal structure and methods provide a novel molecular mechanism for modulation of the activity of ERR-&#x3b1; and provide the basis for rational drug design to obtain potent specific ligands for use as modulators of the activity of this new drug target.

Methods to measure dissociation rates for ligands that form reversible covalent bonds

Substituted phenoxy aminothiazolones as estrogen related receptor-&#x3b1; modulators

Co-crystallization of ERR-&#x3b1; with a ligand that forms a reversible covalent bond

A method for the identification of novel compounds that interact and stabilize the ligand binding domain of estrogen-related receptor gamma (ERR&#x3b3;), a methodology for producing diffraction quality crystal structures in the presence of antagonist and agonist ligands, including Bisphenol A, and the identification of novel biologically-active compounds that have an effect on the transcriptional-activating activity of ERR&#x3b3; are disclosed.

Crystallized structure of estrogen related receptor gamma in complex with bisphenol A

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Dionisios Rentzeperis