Neurotropic Pyrimidine Heterocyclic Compounds. I. The Newly Synthesized Pyrimidine Compounds Promote Neurite Outgrowth of GOTO and Neuro 2a Neuroblastoma Cell Lines, and Potentiate Nerve Growth Factor (NGF)-Induced Neurite Sprouting of PC 12 Cells

From the study using cultured human and mouse neuroblastoma cells, we found that a new type of synthetic bicyclic pyrimidine compounds possessing piperazine moiety strongly promoted neurite outgrowth in neuroblastoma cell lines human GOTO and mouse neuro 2a. The most effective compounds of these 2-piperazinopyrimidine derivatives possessing nerve growth factor (NGF)-like activity were 2-piperazino-6-oxo-5, 6-dihydro(7H)pyrrolo[2, 3-d]pyrimidine and 2-piperadino-6-methyl-5-oxo-5, 6-dihydro(7H)pyrrolo[3, 4-d]pyrimidine. The piperazinopyrimidine compounds were also shown to potentiate NGF-induced neurite sprouting of rat pheochromocytoma PC12 cells. The compounds were more effective in cell cultures than isopropylaminopyrimidine (isaxonine) which had been previously developed and then withdrawn. We discussed the merit of the method of the screening of neurotropic compounds by neurite sprouting activity in cultured neuroblastoma cells.