Design,Synthesis And Evaluation Of Antidepressant And Anti-inflammatory Activity Of Quinoxalinone Heterocyclic Derivatives

Quinoxaline derivatives are an important class of heterocyclic compounds,in which N replaces two carbon atoms of the naphthalene ring.In pharmaceutical chemistry and pharmacology,they have absorbed a great deal of attention due to their wide spectrum of biological properties.Part 1,antidepressant activity.Depression is a common psychological disease which seriously affects the physically and mentally healthy life.Depression affects negatively the health-related qruality of life,increases suicide risk and costs of medical care.A series of 5-alkyl-tetrazolo[1,5-a]quinoxaline-4(5H)-one(5a-5t)and heterocyclic compounds 7,9,13-17 were synthesized by condensation,chlorination,hydrazine generation and alkylation reaction.In vivo antidepressant activity of 27 compounds was screened to use the forced swimming test and tail suspension test in mice and the reference drug was fluoxetine.Open field test evaluated the effect of false positive.Pharmacological in vivo tests showed that most compounds of 5a-5t showed antidepressant activity,especially 5-hexyltetrazolo[1,5-?]quinoxalin-4(5H)-one(5d)exhibited stronger activity and decreased the immobility time by 64.27%at dose of 50 mg/kg(FXT,%DID/59.71%).Heterocycles of 5d,7,9 13-17 in the FST exhibited tetrazole was the most significant antidepressant activity active group.5d showed dose-dependency by the dose-effect relationship tests for the doses of 50,25 and 10 mg/kg.The result of 5d in open-field tests indicated it had no significant effect on the locomotor activity compared with the control group.It means that the antidepressant activity of 5d are not the effect of central nervous system stimulant properties and confirms further the antidepressant activity.Part 2,anti-inflammatory activity.Non-steroidal anti-inflammatory drugs are the most prescribed group of drugs in the world.NSAIDs are largely used for the treatment of a huge variety of clinical conditions in order to relieve symptoms related to inflammation.But NSAIDs have a large side effect by the widely used,for example a potential increased risk of gastrointestinal and upper gastrointestinal complications.An ongoing demand for finding anti-inflammatory drugs with high safety and reduce adverse effects,we started from o-phenylenediamine and designed 5-alkyl-4-oxo-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoxa-line-1-carboxamide(14a-14t)about structural transfonnation of compounds IV.In vitro anti-inflammatory activity is in screening for compounds 14a-14t.All the chemical structures of 47 compounds in the two parts were confirmed by Infrared Spectrum,Nuclear Magnetic Resonance and Mass Spectrometry.