SYNTHESIS OF ANTIFOLS AND MECHANISM-BASED INHIBITORS

该项目的长期目标是开发一种新的 抗叶酸剂的化学分类。 具体目标是制备潜在的抗叶酸剂， 氨甲蝶呤上的杂环 甲氨蝶呤（即，蝶啶）被嘧啶并（4，5-d）取代 嘧啶环系统，其与蝶啶是异构体。 的 还原环的存在使得酶过程不同于 DHFR更有可能是目标。 其中一些化合物将 包括在杂环和侧链位点上的N-C连接。 这项调查的理由是需要提供一个代理人 与氨甲喋呤相比， 抗肿瘤化疗剂。 这些化合物的形成主要是由于 标准化学方法。 特别强调， 将被放置在曼尼希反应，以准备一些 目标分子以及一些前体。 通常的 分析和光谱学的化学表征将是 用于所有新结构。 生物学评价将 由可接受和认可的实验室进行，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.