Nonsteroidal Dissociated Glucocorticoid Agonists Containing Azaindoles as Steroid A-Ring Mimetics
Journal of Medicinal Chemistry2010Vol. 53(18), pp. 6681–6698
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Doris Riether, Christian Harcken, Hossein Razavi, Daniel Kuzmich, Thomas D. Gilmore, Jörg Bentzien, Edward J. Pack, Donald Souza, Richard M. Nelson, Alison Kukulka, Tazmeen N. Fadra, Ljiljana Žuvela-Jelaska, Josephine Pelletier, Roger Dinallo, Mark Panzenbeck, Carol Torcellini, Gerald Nabozny, David Thomson
Abstract
Syntheses and structure-activity relationships (SAR) of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain azaindole moieties as A-ring mimetics and display various degrees of in vitro dissociation between gene transrepression and transactivation. Collagen induced arthritis studies in mouse have demonstrated that in vitro dissociated compounds (R)-16 and (R)-37 have steroid-like anti-inflammatory properties with improved metabolic side effect profiles, such as a reduced increase in body fat and serum insulin levels, compared to steroids.
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