新型非典型DAT抑制剂 (S) -CE-123的过程开发和扩展
Eduardo R Perez Gonzalez1, Bernhard Reck2, Predrag Kalaba3
1Fine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), Presidente Prudente 19060-080, São Paulo, Brazil.
ACS omega
|March 25, 2024
概括
研究人员成功地将新型DAT抑制剂 (S-CE-123) 的合成规模扩大到1公斤的临床前批量. 过程修改改善了药物开发的产量,纯度 (>99%) 和反体过量 (95%).
科学领域:
- 药用化学 医学化学
- 过程化学 过程化学
- 药物开发 药物开发
背景情况:
- 大规模合成和千克实验室生产对于先进的药物开发至关重要.
- (S) -CE-123是一种非典型的多巴胺载体 (DAT) 抑制剂,是需要临床前评估的有希望的候选者.
- 过程转移和扩展对于推进候选药物至关重要.
研究的目的:
- 详细介绍了成功的扩大规模和过程优化,用于合成1公斤 (S) -CE-123.
- 为大规模生产适应和实施卡根不对称氧化协议.
- 克服扩展过程中遇到的挑战,提高产品质量.
主要方法:
- 在四步合成中,应用卡根协议对不对称的硫化物到硫氧化物的氧化.
- 最终合成步骤的代优化,包括处理和染色学净化.
- 引入额外的洗步骤以提高产量和反体纯度.
主要成果:
- 一个1公斤重的 (S-CE-123) 临床前批次的成功合成.
- 达到高产品纯度超过99%.
- 获得了最终产品的95%的反体过剩值.
结论:
- 经过修改的合成工艺使 (S-CE-123) 的高效和可扩展的生产成为可能.
- 过程优化成功地解决了扩大规模的挑战,提高了产量和反体过剩.
- (S-CE-123) 的1公斤批量符合临床前药物开发的严格纯度要求.
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