5-Functionalized indazoles as glucocorticoid receptor agonists

Mei Bai; Grant Carr; Russell J Deorazio; Thomas D Friedrich; Svetlana Dobritsa; Kevin Fitzpatrick; Peter R Guzzo; Douglas B Kitchen; Michael A Lynch; Denise Peace; Mohammed Sajad; Alexander Usyatinsky; Mark A Wolf

doi:10.1016/j.bmcl.2010.04.012

5-Functionalized indazoles as glucocorticoid receptor agonists

Bioorg Med Chem Lett. 2010 May 15;20(10):3017-20. doi: 10.1016/j.bmcl.2010.04.012. Epub 2010 Apr 11.

Authors

Mei Bai¹, Grant Carr, Russell J Deorazio, Thomas D Friedrich, Svetlana Dobritsa, Kevin Fitzpatrick, Peter R Guzzo, Douglas B Kitchen, Michael A Lynch, Denise Peace, Mohammed Sajad, Alexander Usyatinsky, Mark A Wolf

Affiliation

¹ AMRI, Albany, NY 12212-5098, USA.

PMID: 20427184
DOI: 10.1016/j.bmcl.2010.04.012

Abstract

An indazole based series of glucocorticoid receptor agonists is reported. The SAR exploration of this scaffold yielded compounds with nanomolar affinity for the glucocorticoid receptor with indications of selectivity for the preferred transrepression mechanism; in vivo efficacy was observed in the mouse LPS induced TNFalpha model for compound 28.

MeSH terms

Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / pharmacology
Indazoles / chemical synthesis
Indazoles / chemistry*
Indazoles / pharmacology
Mice
Receptors, Glucocorticoid / agonists*
Receptors, Glucocorticoid / metabolism
Tumor Necrosis Factor-alpha / metabolism

Substances

Anti-Inflammatory Agents
Indazoles
Receptors, Glucocorticoid
Tumor Necrosis Factor-alpha