Synthetic Bioactive Molecules Section, LBC, NIDDK, NIH, 8 Center Drive, Room 404, Bethesda, Maryland 20892, United States.
Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
J Med Chem. 2021 Apr 8;64(7):3508-3545. doi: 10.1021/acs.jmedchem.0c01808. Epub 2021 Mar 25.
Over the years, researchers in drug discovery have taken advantage of the use of privileged structures to design innovative hit/lead molecules. The α-ketoamide motif is found in many natural products, and it has been widely exploited by medicinal chemists to develop compounds tailored to a vast range of biological targets, thus presenting clinical potential for a plethora of pathological conditions. The purpose of this perspective is to provide insights into the versatility of this chemical moiety as a privileged structure in drug discovery. After a brief analysis of its physical-chemical features and synthetic procedures to obtain it, α-ketoamide-based classes of compounds are reported according to the application of this motif as either a nonreactive or reactive moiety. The goal is to highlight those aspects that may be useful to understanding the perspectives of employing the α-ketoamide moiety in the rational design of compounds able to interact with a specific target.
多年来，药物发现研究人员利用优势结构来设计创新的命中/先导分子。α-酮酰胺基序存在于许多天然产物中，它已被药物化学家广泛利用来开发针对广泛的生物靶标的化合物，从而为众多病理状况提供了临床潜力。本文的目的是提供对该化学部分作为药物发现中的优势结构的多功能性的深入了解。在简要分析其物理化学特性和合成方法以获得它之后，根据该基序作为非反应性或反应性部分的应用，报告了基于α-酮酰胺的化合物类别。目标是突出那些可能有助于理解在合理设计能够与特定靶标相互作用的化合物中使用α-酮酰胺部分的观点的方面。
