Study On Design, Synthesis And Bioactivity Of 7H-thiazolo [3, 2-b][1, 2, 4]Triazin-7-one Derivatives

Alzheimer’s Disease(AD), is a disease of the central nervous system, a degenerative disease, with the progressing cognitive disorder and the decrescence of memory. AD is one type of senile dementia,can seriously injury the physical health of AD patients,with the aggravation of social ageing phenomena, AD gradually become a rigorous and complicated problem clinically and socially. The main pathophenomenon is cerebral atrophy,β-amyloid and neurofibrillary tangles of the brain tissue.Pathology study found that cholinergic nerve had a retrogression change in the brain of AD patients, and the AD patients’symptom could be improved when the concentration of ACh was increased.Acetylcholinesterase is the most critical enzyme during the nerve conduction of the organism. It is found between the cholinergic synapse, it promotes the hydrolysis of the neurotransmitter acetylcholine at the cholinergic synapses with liberation of choline.Because of its central role in the neurotransmission system, the AChE has been attractive target for the rational design of mechanism-based inhibitors.Firstly phenylglyoxylic acid was made from styrene by oxidation, then 3,4-dihydro-6-phenyl-3-thio-1,2,4-triazin-5(2H)-one was synthesized, then a condensation withα-chloroaceto phenone derivatives to form 18 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives.Target compounds were characterized by 1H-NMR, IR, GC-MS and LC-MS,among them 17 compounds were not yet reported in the literature.According to the Ellman experiments, in comparison to the huperzine A, the inhibitory acetylcholineterase activities of the target compounds were tested. Some of the target compounds such as 6-phenyl-3-(4-hydroxyphenyl)-7H-thiazolo[3,2-b][1,2,4]triazin-7-one (YL03),6-phenyl-3-(2-hydroxy-4-methylphenyl)-7H-thiazolo[3,2-b][1,2,4]triazin-7-one(YL08),3,6-diphenyl-7H-thiaz olo[3,2-b][1,2,4]triazin-7-one (YL10),6-phenyl-3-(4-hydroxy-3-methylphenyl)-7H-thiazolo[3,2-b] [1,2,4]triazin-7-one (YL12),6-phenyl-3-{4-[(2-diethylamino)-2-oxoethoxy]phenyl}-7H-thiazolo [3,2-b][1,2,4]triazin-7-one (YL13),6-phenyl-3-{4-[(2-dimethylamino)-2-oxoethoxy]phenyl}-7H-thiazolo[3,2-b][1,2,4]triazin-7-one (YL14),6-phenyl-3-{4-[2-(4-morpholinyl)-2-oxoethoxy]phenyl} -7H-thiazolo[3,2-b][1,2,4]triazin-7-one (YL16),6-phenyl-3-{4-[2-(4-piperidinyl)ethoxy]phenyl}-7H-thiazolo[3,2-b][1,2,4]triazin-7-one (YL18)showed inhibitory activity on acetylcholineterase. The structure and inhibitory activity relationship of target compounds were surveyed.