A minimalist fragment approach for the design of natural-product-like synthetic scaffolds

Abstract

Chemistry groups involved in drug discovery continue to devote their efforts to improving compound design with the aim of identifying new drug candidates. Many crucial factors must be considered, including: chemical stability, synthetic difficulty, chemical complexity and diversity, ADMET properties, cost, chemical novelty and intellectual property issues, and 'biological appropriateness'. With regard to the latter point, natural products offer an outstanding source of biologically active molecules that provide many useful features that enable us to design innovative, biologically biased, synthetic compounds. This article outlines the recent approaches in this area and suggests a simple metric to assess synthetic compounds for natural product likeness.