Synthesis of Non-GMP Small Molecules

非 GMP 小分子的合成

• 批准号: 8014331
• 负责人: MARY TANGA
• 金额: $ 90.9万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-29 至 2011-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8014331
• 关键词: Antineoplastic Agents; Arts; Biological; Biological Factors; Chemicals; Chemistry; Combinatorial Synthesis; Contracts; Development; Developmental Therapeutics Program; Division of Cancer Treatment and Diagnosis; Evaluation; Extramural Activities; Heterocyclic Steroids; Lead; Libraries; Malignant Neoplasms; Methodology; Methods; Mission; Pharmacodynamics; Property; Rapid Access to Intervention Development; Recommendation; Resources; Series; Staging; United States National Institutes of Health; Work; analog; chemical synthesis; drug development; improved; novel; programs; small molecule; steroid analog

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

发育治疗计划（DTP）的任务是开发新型合成和将天然产物作为潜在的抗癌剂的特征。为了实现这一任务，合同将致力于癌症治疗和诊断分区（DCTD）和其他NIH划分所需的小分子的综合。 该合同将为药物开发计划的早期阶段提供基本的综合支持。为合成的小分子包括各种结构类别；例如，碳循环，杂环，类固醇类似物和天然产物。它们源自快速进入干预开发（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NCI计划。该合同涉及的合成工作中约有90％来自当前的突袭和R*a*n*d程序，以及壁外应用。在R*a*n*d程序的范围下，合成了有限系列的类似物，以改善铅化合物的能力和药效学特性，在该化合物中，还进行了核心化学的建立良好或文化较少的情况。其余10％的工作源自OC和其他NCI，NIH计划的要求。所有重新合成化合物和中间体的纯度和身份都是通过最先进的物理化学方法建立的。合成的数量将从200 mg到100克不等。 合同的总体目的是``非GMP？non-GMP？取得了癌症计划所需的良好纯度化合物的化学合成，例如由RAID和RAID和R*A*n*d程序引起的合成化合物，以及由生物学评估委员会的建议引起的化合物。现有合同不用于合成组合图书馆或由此类库产生的潜在客户。新合同将用于使用平行综合方法的活性单个化合物铅及其类似物的目的，如r*a*a*n*d程序所要求的那样