Structural Simplification of Natural Products

被引：193
作者：
Wang, Shengzheng [1 ,2 ]
Dong, Guoqiang [1 ]
Sheng, Chunquan [1 ]
机构：
[1] Second Mil Med Univ, Sch Pharm, Dept Med Chem, 325 Guohe Rd, Shanghai 200433, Peoples R China
[2] Fourth Mil Med Univ, Sch Pharm, Dept Med Chem, 169 Changle West Rd, Xian 710032, Shaanxi, Peoples R China
来源：
CHEMICAL REVIEWS | 2019年 / 119卷 / 06期
基金：
中国国家自然科学基金; 国家重点研发计划;
关键词：
BIOLOGY-ORIENTED SYNTHESIS; ISOZYME-SELECTIVE INHIBITORS; VERATRUM-CALIFORNICUM DURAND; MACROCYCLIC KETONE ANALOGS; TOPOISOMERASE-I INHIBITORS; STREPTOMYCES SP A92-308110; CELL-MIGRATION INHIBITORS; DIVERTED TOTAL-SYNTHESIS; 1ST MEMBRANE STEP; KINASE-C AFFINITY;
D O I：
10.1021/acs.chemrev.8b00504
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Natural products (NPs) are important sources of clinical drugs due to their structural diversity and biological prevalidation. However, the structural complexity of NPs leads to synthetic difficulties, unfavorable pharmacokinetic profiles, and poor drug-likeness. Structural simplification by truncating unnecessary substructures is a powerful strategy for overcoming these limitations and improving the efficiency and success rate of NP-based drug development. Herein, we will provide a comprehensive review of the structural simplification of NPs with a focus on design strategies, case studies, and new technologies. In particular, a number of successful examples leading to marketed drugs or drug candidates will be discussed in detail to illustrate how structural simplification is applied in lead optimization of NPs.
引用
收藏
页码：4180 / 4220
页数：41
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