2-Phenyl-3-pyridinyl substituted 7-azaindoles as inhibitors of mitogen-activated protein kinase

Abstract

This patent application describes a class of fused pyrrole derivatives that are reported to inhibit the release of the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α) in a cellular assay and modulate the inflammatory effects in an arthritis-induced animal model. As such, these compounds could have therapeutic utility in diseases such as arthritis and asthma. In addition, these molecules are claimed as glucagon inhibitors and therefore, could have a beneficial effect on patients with high levels of hepatic glucose production. The compounds claimed in this application, while not described as p38 mitogen-activated protein kinase (MAPK) inhibitors, contain some of the same pharmacophores as a series of potent p38 MAPK inhibitors recently described by SmithKline Beecham.

• anti-inflammatory
• cytokines
• mitogen-activated protein kinase
• p38
• tumour necrosis factor