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
  • 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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