Synthesis of Non-GMP Small Molecules

开发治疗学计划（DTP）的使命是开发新型合成和表征的天然产物作为潜在的抗癌剂。为了实现这一使命，该合同将致力于合成癌症治疗和诊断部（DCTD）和NIH其他部门的各种计划所需的小分子。 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。指定用于合成的小分子包括多种结构类别;例如，碳环化合物、杂环化合物、类固醇类似物和天然产物。它们来自快速获取干预开发（RAID），快速获取NCI发现资源（R*A*N*D）计划，生物评估委员会（BEC），运营委员会（OC）建议以及其他NCI和NIH计划。约90%的合成工作涉及这一合同起源于目前的RAID和R*A*N*D计划，并从校外申请人。在R*A*N*D计划的范围内，还进行了有限系列类似物的合成，以改善先导化合物的效价和药效学特性，其中核心化学是公认的或记录较少。其余10%的工作是应OC和其他NCI，NIH项目的要求而开展的。所有再合成化合物和中间体的纯度和鉴别均通过最先进的物理化学方法确定。合成的量从200毫克到100克不等。 该合同的总体目标将是癌症项目所需的高纯度化合物的非GMP化学合成，例如RAID和R*A*N*D项目所要求的合成化合物，以及生物评估委员会推荐的化合物。现有合同不用于合成组合文库或由此类文库产生的先导物。根据R*A*N*D计划的要求，新合同将用于使用平行合成方法合成活性单一化合物先导化合物及其类似物

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 Rapid Access To Intervention Development (RAID), Rapid Access to NCI Discovery Resources ( R*A*N*D) programs, Biological Evaluation Committee (BEC), Operating Committee (OC) recommendations, and other NCI, and NIH programs. About 90% of the synthesis work involved in this contract originated from the current RAID and R*A*N*D programs, and from extramural applicants. Under the scope of the R*A*N*D program, 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 upon the request of the OC and 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 program, such as synthetic compounds prompted by the RAID and R*A*N*D programs, and compounds arising from recommendation of the Biological Evaluation Committee. The existing contract is not utilized for the synthesis of combinatorial libraries or leads resulting from such libraries. 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 R*A*N*D program