Discovery of a Novel 2,3,11,11A-Tetrahydro-1h-pyrazino[1,2-b]isoquinoline-1,4(6h)-dione Series Promoting Neurogenesis of Human Neural Progenitor Cells

A novel neurogenic compound (1), discovered from a mouse neural progenitor cell (NPC) screen, showed profound neurogenic effect on human NPCs. Synthesis and SAR of this novel 2,3,11,11a-tetrahydro-1H-pyrazino[1,2-b]isoquinoline-1,4(6H)-dione series are described. Compound 20 is brain penetrable in rodents, and promotes neurogenesis in wild type mice, therefore it is a good tool molecule to study neurogenesis induction as a potential treatment for conditions associated with neurogenesis impairment diseases.