Harcken, Christian; Riether, Doris; Kuzmich, Daniel; Liu, Pingrong; Betageri, Raj; Ralph, Mark; Emmanuel, Michel; Reeves, Jonathan T.; Berry, Angela; Souza, Donald; Nelson, Richard M.; Kukulka, Alison; Fadra, Tazmeen N.; Zuvela-Jelaska, Ljiljana; Dinallo, Roger; Bentzien, Jorg; Nabozny, Gerald H.; Thomson, David S. published the artcile< Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects>, Application In Synthesis of 20744-39-2, the main research area is nonsteroidal glucocorticoid receptor agonist antiinflammatory reduced bone side effect.
Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain “”diazaindole”” moieties and display different transcriptional regulatory profiles in vitro and are considered “”dissociated”” between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of the R enantiomers of I and II. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclin. in vivo model.
Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Application In Synthesis of 20744-39-2.
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem