"市场"中的自然产品:合成与生物学之间的交互
Benjamin J Huffman1, Ryan A Shenvi1
1Department of Chemistry , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States.
Journal of the American Chemical Society
|January 26, 2019
概括
自然产品 (NP) 类似物是药物发现的关键,由于合成处理能力的提高,它们比自然产品具有优势. 开发NP类似物扩大化学多样性以发现和临床进展.
科学领域:
- 医学化学
- 药物发现
- 有机合成
背景情况:
- 药物发现依赖于选化合物集合,平衡多样性,物理化学性质,复杂性和合成可访问性.
- 自然产品在多样性,可取性和复杂性方面表现出色,但往往缺乏合成可处理性.
- 学术研究的重点是合成NP的线索和类型,以克服合成的挑战.
研究的目的:
- 突出天然产品类型和NP衍生药物的发展.
- 探索NP类型如何影响复合分析和支架设计.
- 强调NP类型在扩大药物发现的化学多样性的好处.
主要方法:
- 审查自然产品模拟开发的历史例子和成功的NP衍生药物.
- 对NP类型的结构和合成设计进行分析.
- 研究基于NP架构的专注库,以保持理想的分子性质.
主要成果:
- 在已批准的药物中,天然产品类型占主导地位,而不是NP本身.
- NP类型可以改变物理化学特性,解决NP中的核心不稳定性等局限性.
- 专注的NP模拟库保持了区分NP空间的关键分子特性,在临床进展中提供了统计优势.
结论:
- 自然产品类型提供了一个可行的策略,可以利用NP的复杂性,同时提高合成的可访问性.
- 开发NP类似物可以防止化学物质的同质性,并扩大选库中的分子多样性.
- 通过模拟开发加速合成NP动机对于高效的发现和药物开发至关重要.
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