Synthesis of α- and β-Carbolines by a Metalation/Negishi Cross-Coupling/SNAr Reaction Sequence

Carbolines are considered to be privileged scaffolds in medicinal chemistry. An efficient method for the synthesis of α- and β-carbolines from fluoropyridines and 2-haloanilines is reported. This streamlined procedure consists of a four-step directed ortho-lithiation, zincation, Negishi cross-coupling, and intramolecular nucleophilic aromatic substitution, providing access to a diverse set of functionalized carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated.

The Fellowship of Privileged Scaffolds—One Structure to Inhibit Them All

Over the past few years, the application of privileged structure has emerged as a powerful approach to the discovery of new biologically active molecules. Privileged structures are molecular scaffolds with binding properties to the range of different biological targets. Moreover, privileged structures typically exhibit good drug-like properties, thus assuring more drug-like properties of modified compound. Our main objective is to discuss the privileged structures used for the development of antiviral agents.

Substituted Pyrazoles and Their Heteroannulated Analogs—Recent Syntheses and Biological Activities

Pyrazoles are considered privileged scaffolds in medicinal chemistry. Previous reviews have discussed the importance of pyrazoles and their biological activities; however, few have dealt with the chemistry and the biology of heteroannulated derivatives. Therefore, we focused our attention on recent topics, up until 2020, for the synthesis of pyrazoles, their heteroannulated derivatives, and their applications as biologically active moieties. Moreover, we focused on traditional procedures used in the synthesis of pyrazoles.

Special Issue “Recent Advances in the Synthesis, Functionalization and Applications of Pyrazole-Type Compounds”

Pyrazoles and their reduced form, pyrazolines, are considered privileged scaffolds in medicinal chemistry, owing to their remarkable biological activities, physicochemical properties and occurrence in many low-molecular-weight compounds present in several marketed drugs (e [...]

Artificial Intelligence and Cheminformatics-guided Modern Privileged Scaffold Research

With the rapid development of computer science in scopes of theory, software, and hardware, artificial intelligence (mainly in the form of machine learning and more complex deep learning) combined with advanced cheminformatics is playing an increasingly important role in the drug discovery process. This development has also facilitated privileged scaffold-related research. By definition, a privileged scaffold is a structure that frequently occurs in diverse bioactive molecules. It either has a diverse family affinity or is selective to multiple family members in a superfamily, whilst is different from the “frequent hitters” or the “pan-assay interference compounds”. The long history of the use of this concept has witnessed a functional shift from stand-alone technology towards an integrated component in the drug discovery toolbox. Meanwhile, continuing efforts have been dedicated to deepen the understandings of the features of known privileged scaffolds. In this contribution, we focus on the current privileged scaffold-related research driven by state-of-art artificial intelligence approaches and cheminformatics. Representative cases with an emphasis on distinct research aspects are presented, including an update of the knowledge on privileged scaffolds; proof-of-concept tools and workflows to identify privileged scaffolds and to carry on de novo design; informatic SAR models with diversely complex data sets to provide an instructive prediction on new potential molecules bearing privileged scaffolds.