Discovery of Levodopa Prodrug ONO-2160

Abstract

Levodopa known as prodrug of dopamine is one of the most powerful agent for treating Parkinson’s disease (PD). However, pharmacokinetic (PK) profile of Levodopa has issue of its metabolism in peripheral caused short duration. To address this PK issue, we inspired to make Levodopa prodrug to improve Levodopa duration in plasma. We synthesized more than 700 compounds and evaluated dog PK study to find ONO-2160 that had good PK profile in animals. ONO-2160 and dopa decarboxylase inhibitor (DCI) combination showed long duration in both dogs and rodents. ONO-2160 and DCI combination also showed good PK profiles in healthy volunteers and PD patients in Phase I study.