Spiro azepane-oxazolidinones as Kv1.3 potassium channel blockers: WO2010066840

Abstract

This article evaluates a patent application from Solvay Pharmaceuticals, which claims spiro azepane-oxazolidinones as novel blockers of the voltage-gated potassium channel Kv1.3 for the treatment of diabetes, psoriasis, obesity, transplant rejection and T-cell mediated autoimmune diseases such as rheumatoid arthritis and MS. The patent describes a new chemotype of Kv1.3 blockers and thus illustrates the growing interest of the pharmaceutical industry in Kv1.3 as a target of immunosuppression and metabolic disorders. This article briefly summarizes the chemistry and biological data provided in the patent and then compares the new compounds to Kv1.3 blockers previously disclosed by both academia and pharmaceutical companies.

Figure 1

Exemplary compounds and their Kv1.3 blocking activity in rubidium flux.

Figure 2

Structures of Kv1.3 blockers.

Scheme 1

General synthetic route.