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
