| Literature DB >> 21963986 |
Raj Betageri1, Thomas Gilmore, Daniel Kuzmich, Thomas M Kirrane, Jörg Bentzien, Dieter Wiedenmayer, Younes Bekkali, John Regan, Angela Berry, Bachir Latli, Alison J Kukulka, Tazmeen N Fadra, Richard M Nelson, Susan Goldrick, Ljiljana Zuvela-Jelaska, Don Souza, Josephine Pelletier, Roger Dinallo, Mark Panzenbeck, Carol Torcellini, Heewon Lee, Edward Pack, Christian Harcken, Gerald Nabozny, David S Thomson.
Abstract
We report a SAR of non-steroidal glucocorticoid mimetics that utilize indoles as A-ring mimetics. Detailed SAR is discussed with a focus on improving PR and MR selectivity, GR agonism, and in vitro dissociation profile. SAR analysis led to compound (R)-33 which showed high PR and MR selectivity, potent agonist activity, and reduced transactivation activity in the MMTV and aromatase assays. The compound is equipotent to prednisolone in the LPS-TNF model of inflammation. In mouse CIA, at 30 mg/kg compound (R)-33 inhibited disease progression with an efficacy similar to the 3 mg/kg dose of prednisolone.Entities:
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Year: 2011 PMID： 21963986 DOI： 10.1016/j.bmcl.2011.09.018
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823