MAINTENANCE AND OPERATION OF A SYNTHETIC PEPTIDE FACILITY

国家儿童健康与发展研究所的避孕和生殖健康分支支持一个化学合成设施，该设施为分支开发安全有效的避孕剂的方案提供核心服务。该设施向政府提供药品、化学品、化学中间体、类固醇以及光学纯和/或已拆分的非天然氨基酸，这些物质的对映体过量超过99%，或者在商业上无法获得，或者价格过高，供政府进一步开发避孕药具。 具体目标： 化学合成的领域包括：1）口服活性类固醇，包括;{不含17 -乙炔基乙醇的雌激素，口服活性和长效雄激素，例如，睾丸酮bucyclate和7 cm，11 p..二甲基-19-去甲睾酮丁环酸酯和十一酸酯，口服活性7 α-甲基-19-去甲睾酮（MENT）类似物，和孕酮受体调节剂（PRM），例如，CDB-2914，21-取代的类似物，例如，CDB 4124（第二代）和新的衍生物（第三代）与C11 B-4-芳基和C17-α取代基的组合; 2）与牛血清白蛋白以及组胺缀合物连接的类固醇半抗原，用于放射免疫测定（RIA）的开发; 3)用于RIA作为示踪剂和用于代谢研究的放射性标记化合物; 4）杂环化合物，包括二核苷和六氢茚并吡啶非对映体;和5）烷基化亚氨基糖。承包商维护和操作化学合成设施（CSF），能够（l）快速合成实验室规模的数量（1至5克）在小动物中进行初步避孕研究所需的特定化合物，（2）合成相对较大的量政府提供的用于全面抗生育测试的某些药物（不超过1公斤），包括根据现行良好生产规范（cGMP）进行的临床前和临床研究;（3）合成化学品和/或化学中间体（最多< 1 kg），用于其他正在进行的化学品。（4）利用~ 3 H、I~C和~（1251）放射性标记合成化合物，用于药物动力学和代谢研究。

The Contraception and Reproductive Health Branch of the NICHD supports a Chemical Synthesis Facility (CSF) that provides services central to the Branch's programs to develop safe and effective contraceptive agents. This Facility provides the Government with drugs, chemicals, chemical intermediates, steroids, and optically pure and/or resolved unnatural amino acids possessing >99% enantipmeric excess, which are either commercially unavailable or unduly expensive, for further contraceptive development by the Government. Specific Aims: The areas of chemical synthesis include: 1) orally active steroids, including;{ estrogens without 17 -ethynyla1cohol, orally active and long ¿acting androgens, e.g., testosterone bucyclate and 7cm, 11 p..dimethyl-19~nortestosterone bucyclate & undecanoate, orally active 7&a-methyI-19¿nortestosterone (MENT) analogs, and progesterone receptor modulators (PRM),e.g., CDB-2914, 21-suhstituted analogs, e.g., CDB4124 (2nd generation) and novel derivatives (3rd generation) in combination of substititon at CllB-4-aryl and C17&a; 2) steroid haptens linked to bovine serum a1bumin as well as to histamine conjugates for the development of radioimmunoassay (RIA.); 3)radiolabeled compounds for RIA as tracers and for metabolism studies; 4) heterocyclic compounds including seconucleosides and hexahydroindenopyridine diastereomers ; and 5) alkylated iminosugars. The Contractor maintains and operate a Chemical Synthesis Facility (CSF) capable of (l) rapidly synthesizing laboratory scale quantities (1 to 5 grams) of specific chemical compounds required for initial contraceptive investigation in small animals, (2) synthesizing relatively larger quantities (up to <1 kg) of Some drugs for comprehensive antifertility testing by the Government, including preclinical and clinical studies under current Good Manufacturing Practices (cGMP); (3) synthesizing chemicals and/or chemical intermediates (up to < 1 kg) for use in other ongoing chemical. peptide and related contracts and other synthetic chemical contract programs; and (4) radiolabeled synthesis of compounds using 3H, I~C and 1251 for pharmacokinetics and metabolism studies.