Primary Studies On The Synthesis Of HUP-LA And Its Characteristics Of Degradation In Vitro

Alzheimer's disease (AD) is a progressive neuro-degenerative disorder characterized by impairments of memory and disturbances of at least other cognitive domain .The incidence of this disease is rising with the age, that in persons age 80 and older is approximately 20%. This disease becomes one of three main diseases causing the old sick with the aging of the world population. Unfortunately the cause of AD is still unclear, so there is not special effective drug to therapy, Up to now remaining the function of degenerative cholinergic neurons is the key to study of AD treatment . So the drug development is focus on cholinesterase inhibitors (ChEI).the well-known blood-brain barrier (BBB) is a main transport barrier of drug entry into the Central Nervous System(CNS). For the brain differing from other organs , there are lots of potential promising drugs are blocked outside or can't be kept in the brain enough time to work . So it is great necessary to study and develop targeting drug delivery for CNS's diseases.we choose the huperzine A , the model drug, to combined with linoleic acid (LA),the necessary polyunsaturated fatty acid. Theprodrug, HUP-LA, is synthesized by esterifying the huperzine A with LA in the presence of DCC and DMAP. The structure of the prodrug was confirmed by UV, IR, MS^ 'H-NMI^ 13C-NMR.This research has studied the prodrug degradation in different PBS ,mouse plasma and mouse tissue homogenate in vitro. These studies show this prodrug is not stable, especially in acidic condition and in mouse plasma.In conclusion, we successfully synthesis a new prodrug , HUP-LA, and primary study some fundamental characters about it's degradation in vitro, and give basic and useful theoretical reference for future study.