Ferreira Leonardo G, Andricopulo Adriano D
Laboratorio de Quimica Medicinal e Computacional, Centro de Pesquisa e Inovacao em Biodiversidade e Farmacos, Instituto de Física de Sao Carlos, Universidade de Sao Paulo, Av. Joao Dagnone 1100, 13563-120, Sao Carlos, SP, Brazil.
Curr Top Med Chem. 2017;17(20):2260-2270. doi: 10.2174/1568026617666170224113437.
Fragment-based drug discovery (FBDD) is a broadly used strategy in structure-guided ligand design, whereby low-molecular weight hits move from lead-like to drug-like compounds. Over the past 15 years, an increasingly important role of the integration of these strategies into industrial and academic research platforms has been successfully established, allowing outstanding contributions to drug discovery. One important factor for the current prominence of FBDD is the better coverage of the chemical space provided by fragment-like libraries. The development of the field relies on two features: (i) the growing number of structurally characterized drug targets and (ii) the enormous chemical diversity available for experimental and virtual screenings. Indeed, fragment-based campaigns have contributed to address major challenges in lead optimization, such as the appropriate physicochemical profile of clinical candidates. This perspective paper outlines the usefulness and applications of FBDD approaches in medicinal chemistry and drug design.
基于片段的药物发现（FBDD）是结构导向配体设计中广泛使用的策略，通过该策略，低分子量的活性化合物从类先导化合物转变为类药物化合物。在过去15年中，这些策略成功地融入工业和学术研究平台，发挥了越来越重要的作用，为药物发现做出了卓越贡献。FBDD目前受到关注的一个重要因素是类片段库对化学空间有更好的覆盖。该领域的发展依赖于两个特点：（i）结构已明确的药物靶点数量不断增加，以及（ii）可用于实验和虚拟筛选的巨大化学多样性。事实上，基于片段的研究活动有助于应对先导化合物优化中的重大挑战，例如临床候选药物合适的物理化学性质。这篇观点文章概述了FBDD方法在药物化学和药物设计中的用途及应用。
