新型甾体D环并杂环类化合物的合成及体外抗肿瘤活性研究

发布时间：2018-04-18 08:33

本文选题：甾体杂环 + 去氢表雄酮[17　；参考：《郑州大学》2014年硕士论文

【摘要】：甾体A环或D环与杂环稠合后形成的甾体杂环类化合物，通常具有良好的生物活性，因而受到药物化学家的广泛关注。此外，噻唑结构单元作为活性基团，广泛存在于天然和人工合成具有药理活性的化合物中。本论文以廉价易得的去氢表雄酮为起始原料（DHEA），将噻唑类结构单元引入甾体母核，通过与各种醛缩合并经还原，合成一类新型去氢表雄酮D环并噻唑环亚胺类及亚胺还原类化合物，并对其生物学活性进行初步评。目前，主要研究工作如下： 1.以DHEA为起始原料，通过16-溴代去氢表雄酮与氨基硫脲之间的缩合成环反应，经结晶过滤即可高效经济的得到D-环稠合的2-氨基-噻唑去氢表雄酮，是一种方便有效合成D-环稠合噻唑环的方法。 2.以2-氨基-噻唑去氢表雄酮为底物，合成一系列新型去氢表雄酮D环并[17,16-d]噻唑，去氢表雄酮D环并[1,2-b]吡啶和去氢表雄酮D环并[17,16-d]噻唑并[2,1-b]咪唑类化合物。体外抗癌活性研究表明，大多数化合物对EC109、EC9706和MGC803细胞系具有较好的抑制作用。 3.首次合成一系列新型甾体D环并杂环类化合物。所有甾体杂环化合物的结构都经1H NMR、13C NMR和HRMS确证。
[Abstract]:The steroidal heterocyclic compounds formed by the thickening of A or D rings with heterocycles usually have good biological activity and have been widely concerned by pharmacologists.In addition, thiazole structural units, as active groups, widely exist in natural and synthetic compounds with pharmacological activities.In this paper, the thiazole structural unit was introduced into the steroidal parent nucleus from the cheap and easily available dehydroepiandrosterone (DHEAA), which was condensed with various aldehydes and reduced.A class of novel dehydroepiandrosterone D-ring thiazolyl ring imines and imines were synthesized and their biological activities were preliminarily evaluated.At present, the main research work is as follows:1.Using DHEA as the starting material, 2-aminothiazole-dehydroepiandrosterone (DHEA) was synthesized by condensation reaction between 16-bromodehydroepiandrosterone and thiosemicarbazone through crystallization filtration, and then the 2-aminothiazole dehydroepiandrosterone was obtained efficiently and economically.It is a convenient and effective method for the synthesis of D-ring fused thiazole ring.2.Using 2-aminothiazole-dehydroepiandrosterone as the substrate, a series of new dehydroepiandrosterone D-ring [17o16-d] thiazole, dehydroepiandrosterone D-ring and [1o2-b] pyridine and dehydroepiandrosterone D-ring and [17o16-d] thiazolidazole [2zolidazole] imidazole compounds were synthesized.The antitumor activity of most compounds on EC109 cell line EC9706 and MGC803 cell line was studied in vitro.3.A series of new steroid D-ring heterocyclic compounds were synthesized for the first time.The structures of all steroidal heterocyclic compounds were confirmed by 1H NMR 13C NMR and HRMS.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5;R96

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