一个自动化纳米级反应选和微分子级合成流程的平台
Damith Perera1, Joseph W Tucker2, Shalini Brahmbhatt3
1Pfizer Worldwide Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, CA 92121, USA. sanjeewadamith.perera@pfizer.com paul.f.richardson@pfizer.com neal.sach@pfizer.com.
概括
这项研究介绍了纳米分子级快速反应优化的自动化流合成平台. 该系统通过有效选和合成复杂的药物中间体来加速药物发现.
科学领域:
- 有机化学
- 化学工程
- 制药科学
背景情况:
- 复杂的药物中间体稀缺, 阻碍了药物的发现.
- 对于有效的研究来说,微毫克级反应的优化至关重要.
- 现有的方法缺乏小规模合成的速度和整合性.
研究的目的:
- 开发基于流量的自动化合成平台,用于纳米级反应选和微分子级合成.
- 将快速选和合成整合到一个单一的模块化单元中,使用商业组件.
- 验证该平台在药物研究中的效率和适用性.
主要方法:
- 设计和组装一个自动流合成平台从商用组件.
- 纳米级反应选和微分子级合成能力.
- 在高温下在各种反应条件下使用木-米亚拉合验证该系统.
主要成果:
- 在 24 小时内成功选了 5760 个纳米分子级的苏苏基-米亚拉合反应 (> 1500 个反应/天).
- 为反应变量探索生成了广泛的液体染色体质谱数据.
- 通过多次注射产生所需材料的微分子量,并在毫克尺度上复制最佳条件.
结论:
- 开发的自动流平台可以在亚毫克尺度上有效和快速优化化学反应.
- 这种系统加速了复杂药物中间体的发现和合成.
- 该平台为小规模合成和反应选提供了模块化和多功能解决方案.
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