Synthetic Method Optimization Of Some PDE10A Enezyme Inhibitors

Phosphodiesterase10A is a kind of Dual specificity Phosphodiesterase. Clinical evidence showed that PDE10A inhibitors have anti-schizophrenia activity. It is effective to not only positive symptoms, but also negative symptoms to some extent.The three novel PDE10A inhibitors (PDEIOA-Inhibitor1, Inhibitor2, Inhibitor3) are developed by some pharmaceuitical companies in these years. The PDE1OA-IC50value is less than0.5μM. This paper optimized the synthetic routes for the three inhibitors. After exploration, the total yield for inhibitor1was improved to20%from1.8%, although the total synthetic steps and the longest linear synthetic steps have not been shortened. As for the inhibitior2, the total synthetic steps are shortened to5steps from10steps; the longest linear synthetic steps are shortened to4from7steps and then the total yield for inhibitor2have been improved to65%from7.5%. As for the inhibitior3, the total synthetic steps are shortened to7steps from10steps; the longest linear synthetic steps are shortened to4from6steps and then the total yield for inhibitor3have been improved to28%from0.8%. This paper achieved the goal that the target compounds can be obtained with a good yield in grams scale in a short time.