SYNTHESIS OF ANTIFOLS AND MECHANISM-BASED INHIBITORS

该项目的长期目标是开发一种新的 抗叶酸的化学类别。 具体目的是制备潜在的抗叶酸盐基 甲氨蝶呤上的杂环 甲氨蝶呤(即蝶啶)被嘧啶(4，5-d)取代 嘧啶环系，与蝶啶同分异构体。这个 还原环的存在使酶的过程不同于 Dhfr更有可能成为收购目标。其中一些化合物将 包括杂环和侧链位置上的N-C连接。 这项调查的理由是需要提供一名特工 与甲氨蝶呤相比，不良副作用更少 抗肿瘤化疗药物。 这些化合物的形成主要是由 标准化学方法学。特别是，非常强调 会放在曼尼奇反应上准备一些 靶分子以及一些前体分子。和往常一样 分析和光谱分析的化学表征将是 适用于所有新结构。生物评价将会是 由可接受和认可的实验室进行，例如 美国国家癌症研究所。

The project's long term objectives are the development of a new chemical class of antifolates. The specific aim is the preparation of potential antifolates based loosely on methotrexate in which the heterocyclic ring of methotrexate (i.e., pteridine) is replaced by the pyrimido(4,5-d) pyrimidine ring system, which is isomeric with pteridine. The presence of a reduced ring makes an enzyme process other than DHFR a more likely target. Some of these compounds will include N-C linages at both the heterocyclic and side chain sites. The rationale for this investigation is the need to provide an agent with fewer unwanted side effects than methotrexate as an antitumor chemotherapeutic agent. The formation of these compounds will result primarily from standard chemical methodology. In particular, heavy emphasis will be placed on the Mannich reaction to prepare some of the target molecules as well as some of the precursors. The usual chemical characterization of analysis and spectroscopy will be employed for all new structures. Biological evaluation will be conducted by acceptable and accredited laboratories, such as the National Cancer Institute.