Synthesis of non-GMP Small Molecules

增加的ARRA资金将用于合成和获得文献中已知的抗癌剂；这些可以在国家癌症研究所S抗癌计划中进一步研究。 开发治疗计划(DTP)的任务是开发新的合成和特色化的天然产品作为潜在的抗癌药物。为了完成这项任务，合同将致力于癌症治疗和诊断部(DCTD)和NIH其他部门各种计划所需的小分子合成。该合同将为药物开发计划的早期阶段提供必要的合成支持。用于合成的小分子包括各种结构类别，例如碳环类、杂环类、类固醇类似物和天然产物。它们起源于DCTD、生物评估委员会(BEC)以及其他NCI和NIH项目的下一个倡议。在这些计划的范围内，还进行了一系列有限的类似物的合成，以改善先导化合物的效力和药效学性质，其中核心化学已得到很好的证实或较少有文献记载。剩下的10%的工作是由NCI、NIH发起的。所有重新合成的化合物和中间体的纯度和鉴定都是通过最先进的物理化学方法确定的。合成量从200毫克到100克不等。该合同的总体目标将是癌症NEXT计划所需的高纯度化合物的非GMP化学合成，以及生物评估委员会推荐的化合物。新合同将用于使用并行合成方法合成活性单一化合物引线及其类似物，NCI计划有时会要求这样做。

The addition of ARRA funds will be utilized for synthesis and acquisition of the anticancer agent known in the literature; those can be further studied in the NCI¿s anticancer program. The mission of the Developmental Therapeutics Program (DTP) is the development of novel synthetic and characterized natural products as potential anti-cancer agents. Towards this mission the contract will be devoted to the synthesis of small molecules needed by the various programs of the Division of Cancer Treatment and Diagnosis (DCTD), and other NIH divisions. This contract will provide essential synthesis support for the early stages of the drug development program. The small molecules assigned for the syntheses encompass a variety of structural classes; e.g., carbocyclics, heterocyclics, steroid analogs, and natural products. They originate from the NExT initiative of the DCTD, Biological Evaluation Committee (BEC), and other NCI, and NIH programs. Under the scope of the these programs, the synthesis of a limited series of analogs in order to improve the potencies and pharmacodynamic properties of the lead compound, where the core chemistry is either well established or less documented, were also undertaken. The remaining 10% of the work has originated other NCI, NIH programs. The purity and identity of all resynthesized compounds and intermediates were established by state-of-the-art physico-chemical methods. The quantities synthesized would vary from 200 mg to 100 grams. The overall objective of the contract will be the ¿Non-GMP¿ chemical synthesis of compounds of good purity needed for the cancer NExT program, and compounds arising from recommendation of the Biological Evaluation Committee. The new contract will be utilized for the purpose of synthesis of active single compound leads and their analogs using parallel synthesis methodology, as sometimes required by the NCI programs.