Discovery And Optimisation Of Potent And Highly Subtype Selective Na(V)1.8 Inhibitors With Reduced Cardiovascular Liabilities

Voltage-gated sodium channels, in particular Na(v)1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we describe the discovery and optimisation of a Na(v)1.8 inhibiting phenyl imidazole series that delivers chemical equity that possesses high potency and selectivity and is capable of demonstrating good oral pharmacokinetics.