Synthesis and molecular design of fused deazaflavin-steroid derivatives for biological and pharmacological activities

本研究是合成结构上同时具有两种不同生理或药理活性的稠合化合物。作为药物活性分子设计的一个新尝试，本论文通过对5-脱氮黄素类和甾体类杂合化合物的生物活性增强或新的生物活性的期待，提出了杂合化合物的合成方案，并对杂合化合物的生物活性进行了探索。以上是我在研究期间所取得的研究成果，我们成功地合成了同时具有去氮黄素和甾体结构的杂合化合物。在这些合成中，我们建立了两种简单的合成方法。即第一种方法是在对甲苯磺酸存在下，3-吗啉雄烯与适当的6-氨基-5-甲酰基嘧啶缩合。第二种方法是2-羟基亚甲基的类似缩合 ...更多信息 屈他诺龙与适当的6-氨基嘧啶衍生物。我们尝试了与嘧啶衍生物的缩合反应，不仅与雄甾烷酮，而且与睾酮或胆固醇衍生物。因此，该反应已被用于制备所需的杂合化合物，如脱氮黄素-雄甾烷和脱氮黄素-甾烯。我们成功地合成了杂合化合物，建立在脱氮黄素和类固醇结构在同一时间。在这些合成中，我们建立了两种简单的合成方法。即第一种方法是在对甲苯磺酸存在下，3-吗啉雄烯与适当的6-氨基-5-甲酰基嘧啶缩合。第二种方法是2-羟亚甲基雄甾烷酮与适当的6-氨基嘧啶衍生物的类似缩合。我们尝试了与嘧啶衍生物的缩合反应，不仅与雄甾烷酮，而且与睾酮或胆固醇衍生物。因此，该反应已被用于制备所需的杂合化合物，如去氮杂黄素-雄甾烷和去氮杂黄素-雄甾烯。我们检查了在这里制备的杂合化合物的抗球虫活性作为生物活性的搜索之一。因此，一些杂合化合物显示出比用作阳性对照的氯苯胍更有效的抗球虫活性。因此，这些杂合化合物的生物和药理活性的良好结果将是预期的。少

This research is synthesis of the fused compounds that include two different existent physiological or pharmacological activities structurally at the same time. As a new trial in the active molecular design for drugs, I have made the plan for synthesis of such hybrid compounds like 5-deazaflavins and steroids, by expecting the bioactive potentiation or new bioactivities in the new hybrid compounds, and further I have done the search for the bioactivity of those new hybrid compounds. I describe the above research result that I got in the research period.We succeeded in the synthesis of the hybrid compounds that build in deazaflavin and steroid structures structurally at the same time. In these syntheses, we established the two kinds of simple synthetic methods. Namely the first method was the condensation of 3-morpholinoandrostene with appropriate 6-amino-5-formylpyrimidines in the presence of p-toluenesulfonic acid. The second method was the similar condensation of 2-hydroxymethylenean … More drostanolone with appropriate 6-aminopyrimidine derivatives. We tried the condensation reaction with the pyrimidine derivative and not only androstanolone but also testosterone or cholesterol derivative. The reaction has consequently been useful for the preparation of the desired hybrid compounds such as deazaflavin-androstanes and deazaflavin-cholestenes.We succeeded in the synthesis of the hybrid compounds that build in deazaflavin and steroid structures structurally at the same time. In these syntheses, we established the two kinds of simple synthetic methods. Namely the first method was the condensation of 3-morpholinoandrostene with appropriate 6-amino-5-formylpyrimidines in the presence of p-toluenesulfonic acid. The second method was the similar condensation of 2-hydroxymethyleneandrostanolone with appropriate 6-aminopyrimidine derivatives. We tried the condensation reaction with the pyrimidine derivative and not only androstanolone but also testosterone or cholesterol derivative. The reaction has consequently been useful for the preparation of the desired hybrid compounds such as deazaflavin-androstanes and deazaflavin-cholestenes.We examined the anti-coccidiosis activity for the hybrid compounds prepared here as one of search for the biological activities. Thus, some of the hybrid compounds showed more potent anti-coccidiosis activity than that of robenidine that was used as the positive control. Hereafter, the good result of the biological and pharmacological activities for these hybrid compounds will be expected. Less