抗病毒药物2,5,6-三取代-4(3H)嘧啶酮衍生物的合成及诱导干扰素活性

In order to search for more ideal antiviral drugs,21 substituted pyriiT1idinone derivatives were designed and synthesized,among which 11 were not reported before. The cheinicalstructures were characterized by elemen tal and spectral analysis. The serum interferon - inducing activity was tested in mice. All 2-amino-5-bromo-6-substituted-4-(3H)pyrimidinone compounds were shown to have interferon inducing activity.The corresponding substituted pyrimidine thiones were less active.The new compounds of 6-sulfophenyl derivatives are soluble in、water, but the interferon-inducing activity are not higher than the original compound of ABPP.     

抗病毒药物2，5，6-三取代－4（3H）嘧啶酮衍生物的合成及诱导干扰素活性

抗病毒药物２，５，６-三取代－４（３Ｈ）嘧啶酮衍生物的合成及诱导干扰素活性刘新泳，徐丽君（山东医科大学药学系济南２５００１２）取代嘧啶酮类化合物是一类小分干扰素诱导剂，有抗病毒、抗肿瘤、杀菌抑霉、诱导干扰素和白介素、免疫调节等多种生物活性（１）。目前?..     

Chemotherapy of viral infections

Summary As indicated in Table 1, two approaches have been taken to the development of antiviral chemotherapeutic agents. Both have met with some success although the availability of effective chemotherapeutic agents for the treatment of virus infections is very limited. This situation should change in the near future as more specific, direct inhibitors of virus replication are identified and better ways are developed for stimulating specific and nonspecific host defense mechanisms. Although the discussion of host defenses centered upon the interferon system, there are a variety of other nonspecific host defense mechanisms that are also important including macrophages, lymphocyte subpopulations, and other as yet poorly defined soluble mediators.     

New pyrimidinone and fused pyrimidinone derivatives as potential anticancer chemotherapeutics

A series of novel substituted pyrimidinones and fused pyrimidinones (compounds 3 – 18 ) were synthesized starting with oxiranylmethanone 2 . The in vitro cytotoxicity against a human breast adenocarcinoma (MCF‐7) cell line was investigated and most of the tested compounds showed potent cytotoxic activity against the MCF‐7 cell line comparable to the activity of the commonly used anticancer drug cisplatin. Treatment of MCF‐7 cells with increasing doses (2, 5, 10, and 20 µg/mL) of the tested compounds revealed that the activity of superoxide dismutase and the level of hydrogen peroxide were significantly increased, while the activities of catalase and glutathione peroxidase and the levels of reduced glutathione were significantly lowered compared with control MCF‐7 cells. In general, derivatives 11 and 16 revealed the highest anticancer activity among the tested compounds.     

取代嘧啶酮类抗病毒药物的研究 Ⅰ.2,5,6-三取代-4(3H)嘧啶酮衍生物的合成

设计合成了13个2,5,6-三取代-4(3H)嘧啶酮类衍生物,其中6个是未见文献报道的化合物,化学结构由元素分析、红外光谱证实,并对化合物的抗病毒和诱导干扰素活性进行了初步试验。     

嘧啶酮类化合物的诱导干扰素作用

对新合成的一系列嘧啶酮衍生物,进行了诱导小鼠血清干扰素活性实验。结果表明:凡是2-氨基-5-溴-6-取代-4(3H)嘧啶酮结构的化合物都是活性较强的干扰素诱导剂,其它取代形式则无效或活性降低。新合成的6-对磺酸苯基衍生物,有较高的水溶性,但诱生血清干扰能力降低。所有新合成的化合物诱导干扰素能力都不及 ABPP.     

取代嘧啶酮类抗病毒药物的研究──Ⅲ．嘧啶酮衍生物诱导血清及组织干扰素活性实验

设计合成了１５个取代嘧啶酮衍生物，进行了诱导小鼠血清和组织器官干扰素的活性实验。结果表明，ＡＢＰＰ和ＡＢＭＰ是活性很强的干扰素诱导剂，而相对应的取代嘧啶硫酮化合物ＡＢＰＰＴ和ＡＢＭＰＴ则诱导活性降低；２位氨基是活性必需基因，２位肼基则无效；化合物６－对磺酸笨嘧啶酮类化合物水溶性强，诱导干扰素能力低；其它化合物血清和组织中诱导干扰素能力均不及ＡＢＰＰ和ＡＢＭＰ。