Synthesis Studies On Duloxetine And Its Analogues

In this thesis, Duloxetine as antidepressa nt and its analogues were synthesized.Duloxetine [(S)-N-methyl-3-(naphthalene-1-yloxy)-3-(thiophen-2-yl)-propan-1-amine], as antidepressa nt, is a potent and bala nced in hitibitor of serotonin andnorepinephrine dual-reutake. Duloxetine also can be used for treating other symptomssuch as urinary incontinence, diabetic periphera l neuropathic pain and fibromya lgia.Duloxetine has some features such as improved efficacy, tolerability, safety, fasterrecovery, fewer side effects tha n other antidepressa nt in the clinica l investigations.On the basis of the investigation about the synthetic methods of duloxetine whichis a promising chiral med icine, an economica l and reasonable synthetic route wasstudied and process optimiza tion. Duloxetine hydrochloride was synthesized by stepsof reaction Mannich reachtion, reduction, separation, ethrication, demethylation andsalifica tion from 2-acetylthiophene plus dimethyla mine hydrochloride andparaforma ldehyde.To develop new antidepressa nts, duloxetine analogues were designed based onthe biologica l theory of electronic emission and structure combination two methods;one method is that a new compound was designed based on the biologica l theory ofelectronic emission , duloxetine was used as the mother. The other is that duloxetine reactswith acyl chloride obtaining target compounts, and with chloroacetyl chloride obtaining chloroacetylaminoscompounds, then, treated with aromatic piperazid ines by N-alkyl reactionsynthesizing target compounds. The analogues were characterized by MS & NMR, andthe results are satisfied.