度洛西汀及其衍生物的合成研究-应用化学专业论文.docxVIP

SYNTHESIS STUDIES ON DULOXETINE AND ITS ANALOGUES ABSTRACT In this thesis, Duloxet ine as antidepressa nt and its analogues were synthesized. Duloxet ine [(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 and norepinephrine dual-reutake. Duloxet ine also can be used for treating other symptoms such as urinary incontinence, diabetic periphera l neuropathic pain and fibromya lgia. Duloxet ine has some features such as improved efficacy, tolerability, safety, faster recovery, fewer side effects tha n other antidepressa nt in the clinica l invest igations. On the basis of the invest igation about the synthetic met hods of duloxet ine which is a promising chiral med icine, an economica l and reasonable synthetic route was studied and process optimiza tion. Duloxet ine hydrochlor ide was synthesized by steps of reaction Mannich reachtion, reduct ion, separation, ethrication, demet hylation and salifica tion from 2-acetylthiophene plus dimet hyla mine hydrochlor ide and paraforma ldehyde. To develop new antidepressa nts, duloxet ine analogues were designed based on the biologica l theor y of electronic emission and struct ure combination two met hods; one met hod is that a new compound was designed based on the biologica l theor y of elect ronic emission , duloxet ine was used as the mot her. The other is that duloxetine reacts with acyl chlor ide obtaining target compounts, and with chloroacetyl chlor ide obtaining chloro- acetylaminos compounds, then, treated with aromatic piperazid ines by N-alkyl reaction synthesizing target compounds. The analogues were character ized by MS NMR, and the results are satisfied. KEY WORDS: antidepressa nt, duloxet ine, process optimization, synthesis 原创性声明 本人郑重声明 :所呈交的学位论文，是本人在导师指导下，进行研究工 作所取得的成果。除文中已经注明引用的内容外 ，本学位论文不包含任何他 人或集体 己经发表的作品内容，也不包含本人为获得 其他学位而使用过的 材 料。对本论文所涉及的研究工作做出贡献的其他个人或集体 ，均己在文中以 明确方式标明。本学位论文原创性声明的法律责任由本 人承担. 位论文作者签名:有多 日期:，，0/