2. Academic Validation
  3. Nonsteroidal dissociated glucocorticoid agonists containing azaindoles as steroid A-ring mimetics

Nonsteroidal dissociated glucocorticoid agonists containing azaindoles as steroid A-ring mimetics

  • J Med Chem. 2010 Sep 23;53(18):6681-98. doi: 10.1021/jm100751q.
Doris Riether 1,  Christian Harcken,  Hossein Razavi,  Daniel Kuzmich,  Thomas Gilmore,  Jörg Bentzien,  Edward J Pack,  Donald Souza,  Richard M Nelson,  Alison Kukulka,  Tazmeen N Fadra,  Ljiljana Zuvela-Jelaska,  Josephine Pelletier,  Roger Dinallo,  Mark Panzenbeck,  Carol Torcellini,  Gerald H Nabozny,  David S Thomson
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Department of Immunology and Inflammation, and Drug Discovery Support, Boehringer-Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877, USA. [email protected]
PMID: 20735001 DOI: 10.1021/jm100751q
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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