SYNTHESIS AND EVALUATION OF A BRAIN-TARGETED CATECHOL DERIVATIVE AS APOTENTIAL NGF-INDUCER

A novel brain-targeted catechol derivative was designed for the potent ial in vivo induction of nerve growth factor (NGF) biosynthesis within the central nervous system (CNS) after its peripheral administration. The dihydropyridine-pyridinium salt moiety integrated in the structur e of the catechol and conferred the brain-selective delivery property to the molecule. After preliminary in vitro evaluation of this brain-t argeted derivative and its pyridinium metabolite, in vivo tissue distr ibution studies demonstrated the selective and sustained delivery of t he compound of interest to the brain of a rat. Furthermore, the signif icant in vitro biological activity of the novel catechol derivative th at was demonstrated in the L-M cell line is encouraging for the expect ed NGF-inducing activity of this novel catechol derivative in vivo.