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

本研究是在结构上同时包含两种不同存在的生理或药理活性的融合化合物的合成。作为药物活性分子设计的新尝试，我对5-去氮黄素、类固醇等杂化化合物的合成进行了计划，期待新杂化化合物的生物活性增强或新的生物活性，并对这些新杂化化合物的生物活性进行了研究。我描述了我在研究期间所获得的上述研究成果。我们成功地合成了在结构上同时包含去氮黄素和类固醇结构的杂化化合物。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的存在下，用适当的6-氨基-5-甲酰基嘧啶缩合3- morpholinoandrost烯。第二种方法是用合适的6-氨基嘧啶衍生物缩合2-羟亚甲基。我们尝试了嘧啶衍生物和雄甾酮衍生物以及睾酮或胆固醇衍生物的缩合反应。因此，该反应可用于制备所需的杂化化合物，如去氮黄酮-雄甾烯和去氮黄酮-胆甾烯。我们成功地合成了在结构上同时包含去氮黄素和类固醇结构的杂化化合物。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的存在下，用适当的6-氨基-5-甲酰基嘧啶缩合3- morpholinoandrost烯。第二种方法是2-羟亚甲基雄甾酮与合适的6-氨基嘧啶衍生物进行缩合反应。我们尝试了嘧啶衍生物和雄甾酮衍生物以及睾酮或胆固醇衍生物的缩合反应。因此，该反应可用于制备所需的杂化化合物，如去氮黄酮-雄甾烯和去氮黄酮-胆甾烯。我们对所制备的杂合物进行抗球虫活性检测，作为寻找其生物活性的手段之一。因此，一些杂交化合物的抗球虫活性比作为阳性对照的罗苯定更强。今后，这些杂交化合物的生物学和药理活性将得到良好的结果。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