New indazole derivatives as phosphodiesterase type 4 inhibitors

Abstract

This patent discloses a series of indazole derivatives that exhibit activity as inhibitors of phosphodiesterase type 4 (PDE4) and consequently antagonism of tumour necrosis factor a (TNF-α) release. As such, these compounds would be expected to be useful for the treatment of autoimmune diseases such as asthma, rheumatoid arthritis and septic shock. The novel feature that distinguishes these molecules from closely related PDE4 inhibitors developed by SmithKline Beecham is the indazole functionality. This acts as an effective isostere of the 3-methoxy, 4-cyclopentoxy motif observed in many rolipram-like PDE4 inhibitors (rolipram, compound 1). Standard assay protocols for the field are employed; however, no biological data are presented.

• asthma
• phosphodiesterase
• tumour necrosis factor